One-Minute Telegram Archiv

Letzte Aktualisierung: 23.11.2023

Introductiontoggle arrow icon

This article contains a collection of content written for the One-Minute Telegram, a biweekly newsletter that presents the newest medical research condensed into just one minute of reading. This newsletter is designed for all of our colleagues who want to stay current on the latest medical literature without having to comb through and dissect medical studies themselves. It is peer-reviewed by our team of physician editors and integrated into the Amboss library. Even after a long night shift or a busy day on the wards, it should go down easy. Sign up via the link in “Tips and Links” below.

See also our One-Minute Telegram Archiv 2022, One-Minute Telegram Archiv 2021 and One-Minute Telegram Archiv 2020.

Q4 2023toggle arrow icon

Edition 87 - November 18, 2023toggle arrow icon

AI-guided treatment of depression: a byte-sized breakthrough?

One-Minute Telegram 87-2023-1/3

10-second takeaway

Artificial intelligence (AI) is increasingly present in our lives, but its role in primary care remains unclear. This investigation found that ChatGPT-3.5 and ChatGPT-4 outperformed primary care physicians (PCPs) in the initial treatment of depression based on adherence to clinical guidelines and avoidance of gender and socioeconomic bias. AI chatbots may be helpful tools for guideline-based clinical decision-making, but real-world patient care can demand approaches that extend beyond clinical guidelines.

Study breakdown

  • Study purpose: to compare treatment recommendations for depression given by AI chatbots and PCPs in France
  • Methods
    • Case vignettes of new patients with depressive symptoms (with varied gender, socioeconomic status, and symptom severity) from a previous study were input into ChatGPT interfaces.
    • The chatbot was prompted with, “What do you think a primary care physician should suggest in this situation?”
    • If pharmacotherapy was recommended, the chatbot was prompted to select an antidepressant, anxiolytic/hypnotic, a combination of both, or none.
    • ChatGPT’s responses were compared to those of 1249 PCPs who had participated in the previous study.
  • Main results
    • For mild depression (most guidelines recommend psychotherapy alone):
      • AI more frequently proposed psychotherapy alone: ChatGPT-4 98%, ChatGPT-3.5 95%, PCPs 4%.
      • AI less frequently proposed pharmacotherapy alone: ChatGPT-4 0%, ChatGPT-3.5 0%, PCPs 48%.
    • For severe depression (most guidelines recommend a combination of pharmacotherapy and psychotherapy):
      • AI more frequently proposed a combination of pharmacotherapy and psychotherapy: ChatGPT-4 100%, ChatGPT-3.5 72%, PCPs 44%.
      • AI less frequently proposed pharmacotherapy alone: ChatGPT-4 0%, ChatGPT-3.5 0%, PCPs 40%.
      • AI less frequently proposed no therapy: ChatGPT-4 0%, ChatGPT-3.5 0%, PCPs 10%.
    • When pharmacotherapy was recommended (most guidelines recommend an antidepressant alone):
      • Most AI recommendations were for an antidepressant alone: ChatGPT-4 68%, ChatGPT-3.5 74%.
      • Most PCPs recommended an antidepressant combined with an anxiolytic/hypnotic (67%).
    • Gender and socioeconomic biases were observed among PCPs, but not with AI.
  • Limitations include:
    • Participating PCPs were exclusively based in France, limiting generalizability.
    • Given the iterative nature of AI software, performance during the study may not represent the performance of subsequent versions of ChatGPT.
    • The use of clinical vignettes may not adequately reflect real-world doctor–patient interactions and considerations.
  • Study funding: Not declared
  • Original study: Identifying depression and its determinants upon initiating treatment: ChatGPT versus primary care physicians [1]
  • Related AMBOSS articles: Unipolare Depression

Breathe easier: a breakthrough in preventing ventilator-associated pneumonia

One-Minute Telegram 87-2023-2/3

10-second takeaway

Addressing the ongoing challenge of ventilator-associated pneumonia (VAP) in critically ill patients, this large, randomized control trial (AMIKINHAL) demonstrated that 3 days of preventive inhaled amikacin in mechanically ventilated patients significantly reduced the incidence of VAP over 28 days. Inhaled antibiotics may be an important tool in the armamentarium against this common iatrogenic illness.

Study breakdown

  • Study population: 850 adult ICU patients (mean age, 61–62 years; 34% female) without suspected or confirmed VAP, kidney injury, tracheostomy, planned extubation within 24 hours, or current aminoglycoside therapy who had been undergoing mechanical ventilation for 72–96 hours
  • Methods: multicenter, randomized, double-blind, placebo-controlled trial in France
    • Randomized 1:1 to inhaled amikacin (20 mg/kg ideal body weight) or placebo once daily for 3 days
    • Primary outcome: first episode of VAP within 28 days
    • Secondary outcomes included infection-related ventilator-associated complications, e.g., worsening oxygenation.
    • Safety outcomes included increased resistance in the expiratory limb and bronchospasm.
    • Follow-up: 28 days
  • Main results
    • The amikacin group had a lower incidence of VAP (15%) than the placebo group (22%): HR, 1.5; 95% CI, 0.6–2.5.
    • The amikacin group had fewer infection-related ventilator-associated complications (18%) than the placebo group (26%): HR, 0.66; 0.5–0.9.
    • Trial-related serious adverse effects did not significantly differ between the amikacin group (1.7%) and the placebo group (0.9%): P = 0.38.
  • Limitations include:
    • The trial was not powered to detect a difference in patient-centered outcomes such as death or length of ICU stay.
    • Single-country study design limits generalizability.
    • In the absence of a standard care comparison group, the possibility that normal saline placebo increased the risk of VAP in the control group cannot be ruled out.
  • Study funding: French Ministry of Health
  • Original study: Inhaled amikacin to prevent ventilator-associated pneumonia [2]
  • Related AMBOSS articles: Pneumonie | Nosokomiale Infektionen

Memory lane: dementia risk is increased in adult-onset ADHD

One-Minute Telegram 87-2023-3/3

10-second takeaway

Adult-onset attention-deficit/hyperactivity disorder (ADHD) is not well studied but has some similar cognitive symptoms to dementia, suggesting a potential association between these syndromes. This large cohort study found an almost threefold increase in the risk of dementia in individuals with adult-onset ADHD compared to those without ADHD. Although further research is needed to confirm this relationship, health care providers may wish to increase their vigilance for adult-onset ADHD as part of their efforts to manage dementia.

Study breakdown

  • Study population: 109,218 Israeli citizens aged 51–70 years (52% female) without a history of ADHD or dementia
  • Methods: prospective national cohort study
    • Participants were enrolled from a single health maintenance organization database.
    • Participants were followed from January 1, 2003, to February 28, 2020.
    • Adults with ADHD and dementia were identified based on ICD-9 and ICD-10 codes.
  • Main results
    • 0.7% of participants received a new diagnosis of ADHD.
    • 7.1% of participants received a new diagnosis of dementia.
    • The incidence of dementia was significantly higher in participants with ADHD (13.2%) than those without ADHD (7.0%): adjusted HR, 2.77; 95% CI, 2.11–3.63; P < 0.001.
    • There was no increase in the risk of dementia in participants with ADHD who received psychostimulant medication.
  • Limitations include:
    • Rates of ADHD and dementia diagnoses were ascertained from medical records, so the true incidences may have been underestimated.
    • The reliability of ADHD and dementia diagnoses could not be ascertained.
    • The study design does not allow for the inference of causation, residual confounding to be ruled out, or the significance of the effects of psychostimulant medication on dementia to be analyzed.
  • Study funding: Israeli National Insurance Institute
  • Original study: Adult attention-deficit/hyperactivity disorder and the risk of dementia [3]
  • Related AMBOSS articles: Demenz | ADHS

Edition 86 - November 4, 2023toggle arrow icon

Guideline-based preventive care could save a Million Hearts

One-Minute Telegram 86-2023-1/3

10-second takeaway

Cardiovascular disease (CVD) is the leading cause of death in the US. The Million Hearts Model, an initiative that provided extra financial incentives for organizations to follow guideline-based CVD prevention, resulted in modestly better outcomes for individuals with high or medium CVD risk without increasing Medicare spending. Organizations should continue to explore ways to optimize clinicians’ and patients’ ability to follow guideline-based CVD preventive care.

Study breakdown

  • Study population: 218,864 Medicare fee-for-service beneficiaries aged 40–79 years (median age, 72–73 years; 58% men; 7% Black) with a medium or high 10-year CVD risk (defined as CVD risk score ≥ 15%) without a history of MI, stroke, kidney failure, or hospice care
  • Methods: pragmatic cluster randomized clinical trial from 2017 to 2021 (Million Hearts CVD Risk Reduction Model)
    • 342 health care organizations randomized 1:1 to ACC/AHA guideline-based CVD preventive care (intervention) or standard care (control)
    • Intervention: Organizations were paid to monitor and reduce CVD risk.
    • Primary outcomes
      • First-time CVD events (MI, stroke, TIA)
      • Medicare spending per beneficiary for the first CVD event
    • Key secondary outcomes
      • Combined first-time CVD events and deaths, and deaths alone
      • Medicare spending per beneficiary
    • Follow-up: 5 years
  • Main results
    • Compared to the control group, the intervention group had:
      • Fewer first-time CVD events (not statistically significant): 15.8 vs. 17 per 1000 person-years; adjusted HR (aHR), 0.97 (90% CI, 0.93–1)
      • Fewer combined first-time CVD event and deaths: 18.7 vs. 20.3 per 1000 person-years; aHR, 0.96 (0.93–0.99)
      • Lower death rate: 28 vs. 29.7 per 1000 person-years; aHR, 0.96 (0.93– 0.98)
    • Results differed for high and medium CVD risk populations.
      • Medium-risk patients (CVD risk score 15–29%): significant decrease in first-time CVD events and deaths
      • High-risk patients (CVD risk score ≥ 30%): no significant decrease in first-time CVD events, but significant decrease in deaths
    • General Medicare spending and Medicare spending per beneficiary per month were similar in both groups.
  • Limitations include:
    • Randomized organizations had a high dropout rate, which may have biased the outcomes.
    • Results may not be generalizable to organizations that do not participate in Medicare fee-for-service.
    • CVD events were captured by Medicare claims, and therefore events that did not result in hospitalization or an ED visit and any care received within a different system (e.g., the VA) were not included.
    • Medication adherence was not assessed.
  • Study funding: Centers for Medicare and Medicaid Services, Department of Health and Human Services
  • Original study: Effects of the Million Hearts Model on myocardial infarctions, strokes, and Medicare spending: a randomized clinical trial [4]
  • Related AMBOSS articles: Atherosklerose und kardiovaskuläre Prävention | Ischämischer Schlaganfall | Akutes Koronarsyndrom

Dex does not pass the test in patients with TB meningitis and HIV

One-Minute Telegram 86-2023-2/3

10-second takeaway

Patients with HIV who develop tuberculous meningitis have a high mortality rate; adjunctive glucocorticoids are often used to improve outcomes despite the lack of data supporting their safety and efficacy. This small RCT found no significant benefit for treatment with adjunctive dexamethasone compared to standard treatment alone. More research is needed to identify therapies that can improve survival rates in this population.

Study breakdown

  • Study population: 520 adults (median age, 36 years; 76% male) with HIV and tuberculous meningitis who were newly receiving (for ≤ 6 days) or planned to receive antituberculosis therapy
  • Methods: double-blind, randomized, placebo-controlled trial in Vietnam and Indonesia
    • Randomized 1:1 to receive a 6–8-week tapering course of dexamethasone or placebo
    • All participants also received standard antituberculosis therapy and antiretroviral therapy.
    • Primary endpoint: 1-year all-cause mortality
    • Key secondary endpoints included neurological outcomes (e.g., neurological disability at 12 months, shunt surgery), new AIDS-defining event or death, and serious adverse events.
    • Follow-up: 12 months
  • Main results
    • All-cause mortality was not significantly different in the dexamethasone group (44.1%) compared to the placebo group (49%): HR, 0.85; 95% CI, 0.66–1.10.
      Serious adverse events and secondary endpoints were similar in both groups.
  • Limitations include:
    • Over 25% of participants in both groups received additional open-label glucocorticoids during treatment, which increases the risk of bias.
    • Findings may not be generalizable.
      • A large proportion of participants had severe immunosuppression and/or had never received antiretroviral therapy.
      • The trial was conducted in settings with limited access to advanced therapies, e.g., ventriculoperitoneal shunting.
  • Study funding: Wellcome Trust
  • Original study: Adjunctive dexamethasone for tuberculous meningitis in HIV-positive adults [5]
  • Related AMBOSS articles: HIV-Infektion

Telemedicine convenience vs. clinical challenges

One-Minute Telegram 86-2023-3/3

10-second takeaway

Since the beginning of the COVID-19 pandemic, telemedicine capacity has rapidly expanded to meet patients’ and clinicians’ needs, but clinical outcomes from the shift toward telemedicine are uncertain. This retrospective study found that patients with an initial telemedicine visit had lower rates of medication prescribing and ordering of lab studies or imaging and higher rates of in-person follow-up visits compared to those who had an initial in-office visit. While telemedicine offers convenience, these findings suggest that virtual visits may not be able to address all clinical concerns.

Study breakdown

  • Study population: 1,589,014 adult primary care patients within an integrated health care delivery system in the US
    • 54.9% female
    • 46.5% White, 22.3% Hispanic, 22.2% Asian, 7.4% Black
    • 21.5% from lower socioeconomic status neighborhoods
    • 31.8% had chronic disease
  • Methods: retrospective study based on electronic health record data
    • Comparison between telemedicine (i.e., telephone visits and video visits) and office visits
    • Primary outcomes
      • Medication prescribing and ordering of imaging or laboratory studies
      • Health care utilization (e.g., in-person visit to primary care or ED, hospitalization) within 7 days of the index visit
    • Patients with COVID-19 or URIs or who had a health care visit within the past 7 days were excluded from the analysis.
    • Follow-up: 7 days
  • Main results
    • 2,357,598 primary care visits took place: 49.2% office, 31.3% telephone, and 19.5% video
    • Office visits resulted in higher rates of prescriptions and tests ordered than telephone or video visits.
      • Prescriptions: 46.8% of office visits, 38.4% of video visits, and 34.6% of telephone visits
      • Lab tests: 41.4% office, 27.4% video, 22.8% telephone
      • Imaging: 20.5% office, 11.9% video, 8.7% telephone
    • In-person follow-up visit rates were significantly higher for patients with an initial telephone or video visit compared to those with an initial office visit.
      • Primary care follow-up: 7.6% after telephone, 6.2% after video, 1.3% after office
      • ED visit: 2.1% after telephone, 1.8% after video, 1.6% after office
      • Hospitalization: 0.25% after telephone, 0.24% after video, 0.21% after office
  • Limitations include:
    • Not generalizable to health care settings without an established telemedicine service or patients who do not have insurance or a primary care physician
    • Reasons for additional in-person health care utilization were not captured.
    • Long-term follow-up was not performed.
  • Study funding: Agency for Healthcare Research and Quality
  • Original study: Telemedicine versus in-person primary care: treatment and follow-up visits [6]
  • Related AMBOSS article: Apps im Gesundheitswesen

Edition 85 - October 21, 2023toggle arrow icon

ECLS no panacea for ischemic cardiogenic shock

One-Minute Telegram 85-2023-1/3

10-second takeaway

The mortality rate in patients with cardiogenic shock after an acute myocardial infarction (MI) is high, even with prompt revascularization, but small studies have suggested that early extracorporeal life support (ECLS) can improve outcomes. This large European study found that in patients with acute ischemic cardiogenic shock and planned revascularization, adding early ECLS to usual medical therapy did not improve survival at 30 days compared to usual medical therapy alone. The search continues for ways to reduce mortality in patients with this high-risk medical condition.

Study breakdown

  • Study population: 420 adults aged 18–80 years (median age, 63 years; 81% men) with acute MI complicated by cardiogenic shock and planned early revascularization
  • Methods: multicenter, open-label trial in Germany and Slovenia
    • Randomized 1:1 to receive ECLS and usual medical therapy (ECLS group) or usual medical therapy alone (control group)
    • Percutaneous coronary intervention was the preferred technique for revascularization.
    • ECLS was started during the initial cardiac catheterization.
    • Primary outcome: death from any cause at 30 days
    • Safety outcomes: bleeding, stroke, significant peripheral vascular complications
  • Main results
    • Death from any cause at 30 days was similar in the ECLS group (48%) and the control group (49%): relative risk, 0.98 (95% CI, 0.80–1.19).
    • The rate of moderate or severe bleeding was higher in the ECLS group (23%) than the control group (10%).
    • The rate of severe peripheral vascular complications was higher in the ECLS group (11%) than the control group (4%).
  • Limitations include:
    • The study was not blinded.
    • There was high crossover between groups, e.g., participants who had refractory cardiac arrest in the control group often received ECLS.
    • The heterogeneity of clinical presentations may have prevented identification of subgroups that could have benefited from ECLS.
    • Women were underrepresented in the study.
  • Study funding: Else Kröner Fresenius Foundation and others
  • Original study: Extracorporeal life support in infarct-related cardiogenic shock [7]
  • Related AMBOSS articles: Schock | Akutes Koronarsyndrom

Aspirin and ASCVD: Is enteric coating beneficial?

One-Minute Telegram 85-2023-2/3

10-second takeaway

Gastrointestinal ulceration and bleeding are potential complications of preventive treatment of atherosclerotic cardiovascular disease (ASCVD) with aspirin. This study found no difference in major bleeding events or clinical effectiveness between participants taking enteric-coated aspirin and those taking uncoated aspirin. However, further research is needed to reliably determine the effect of enteric-coated aspirin on bleeding risk, because findings suggested that enteric-coated aspirin may reduce bleeding but this could not be statistically supported.

Study breakdown

  • Study population: 15,076 adults aged ≥ 18 years (median age, 68 years; 68% men; 84% White, 8.4% Black, 4.5% other) with ASCVD not treated with an oral anticoagulant or ticagrelor and no recent history of GI bleeding
  • Methods: post hoc secondary analysis of a pragmatic, open-label, multicenter, patient-centered randomized clinical trial (ADAPTABLE study)
    • ADAPTABLE study randomized participants 1:1 to receive aspirin 81 mg or 325 mg daily
    • This study further categorized participants based on their initial self-selected aspirin formulation: enteric-coated or uncoated.
    • Primary effectiveness endpoint: time to first occurrence of any event in the composite of death from any cause and hospitalization for MI or stroke
    • Safety endpoint: major bleeding (i.e., hospitalization for intracranial hemorrhage or a bleeding event requiring product transfusion)
  • Main results
    • No difference in primary effectiveness of enteric-coated aspirin compared to uncoated aspirin: adjusted hazard ratio (AHR), 0.94 (95% CI, 0.80–1.09)
    • No significant difference in the incidence of major bleeding between the enteric-coated aspirin group and the uncoated aspirin group: AHR, 0.82 (95% CI, 0.49–1.37); large CI prevents exclusion of significance to the 18% risk reduction in bleeding
    • No difference in effectiveness or incidence of major bleeding between 81 mg and 325 mg doses in either the enteric-coated or uncoated aspirin group
  • Limitations include:
    • Patient selection of aspirin formulation may have led to confounding.
    • Any crossover between groups was not recorded.
    • Incidence of minor GI bleeding was not investigated.
  • Study funding: Patient-Centered Outcomes Research Institute
  • Original study: Effectiveness and safety of enteric-coated vs uncoated aspirin in patients with cardiovascular disease: a secondary analysis of the ADAPTABLE randomized clinical trial [8]
  • Related AMBOSS articles: Atherosklerose und kardiovaskuläre Prävention | Gastrointestinale Blutung

Liberal vs. tight glucose control in the ICU: The sugar saga continues

One-Minute Telegram 85-2023-3/3

10-second takeaway

Hyperglycemia is undisputedly associated with unfavorable outcomes in ICU patients, but the benefit of tight glucose control in this group remains unclear. This large randomized control study found no difference in either length of ICU stay or 90-day mortality with tight glucose control compared to liberal glucose control in ICU patients who did not receive early parenteral nutrition. Further research is needed to clarify the optimal approach for glucose management in ICU patients.

Study breakdown

  • Study population: 9230 adults (median age, 67 years; 63% men) admitted to ICUs in Belgium
  • Methods: prospective, multicenter, randomized, controlled, parallel group trial
    • Randomized 1:1 to target glucose of 180–215 mg/dL (liberal glucose control) or 80–110 mg/dL (tight glucose control)
    • Insulin administration was guided by a computer algorithm and given as a continuous infusion through a central venous catheter.
    • Enteral nutrition was started as soon as possible, but no parenteral nutrition was given in the first week.
    • Primary outcome: length of required ICU care
    • Secondary outcomes included severe acute kidney injury (AKI) and liver dysfunction.
    • Safety outcome: mortality at 90 days
  • Main results
    • Length of required ICU care was similar in the tight-control group and the liberal-control group: HR, 1 (95% CI, 0.96–1.04).
    • Mortality at 90 days was similar in the tight-control group (10.5%) and the liberal-control group (10.1%).
    • Severe hypoglycemia occurred more frequently in the tight-control group (1%) than in the liberal-control group (0.7%).
    • Incidences of severe AKI and liver dysfunction were lower in the tight-control group.
  • Limitations include:
    • The study was not blinded.
    • Change in discharge policies during the COVID-19 pandemic may have led to confounding.
  • Study funding: Research Foundation-Flanders and others
  • Original study: Tight blood-glucose control without early parenteral nutrition in the ICU [9]
  • Related AMBOSS articles: Insulinkorrektur bei Hyperglykämie

Edition 84 - October 7, 2023toggle arrow icon

Continue monitoring BP during pregnancy

One-Minute Telegram 84-2023-1/3

10-second takeaway

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal morbidity and mortality and can result in adverse outcomes for the fetus and newborn. The USPSTF has reaffirmed its previous recommendation to screen for HDP with blood pressure (BP) measurements at all prenatal care visits. Individuals with positive screening should receive evidence-based management.

Recommendation breakdown

  • Recommendation: The USPSTF concluded with moderate certainty that obtaining BP measurements throughout pregnancy to screen for HDP has substantial benefit.
  • Applicable population: all pregnant individuals with no history of HDP or preexisting hypertension
  • Additional information
    • Recommendations for HDP screening
      • Obtain BP measurements at every prenatal care visit.
      • Ensure that the appropriate cuff size is used.
      • If systolic BP is ≥ 140 mm Hg or diastolic ≥ 90 mm Hg, repeat the measurement after at least 4 hours to confirm the finding.
      • Test for proteinuria if screening is positive.
    • During the postpartum period:
      • Educate on clinical features of preeclampsia.
      • Continue BP measurements for individuals with HDP.
    • There is limited evidence that screening for HDP is associated with severe or significant harm.
    • Potential harms of treatment include:
      • Preterm or cesarean delivery
      • Neonatal complications
      • Adverse drug effects
  • Limitations include:
    • Insufficient research on:
      • Screening for HDP during the postpartum period
      • Effect of screening on maternal and perinatal morbidity and mortality
  • Study funding: Agency for Healthcare Research and Quality (AHRQ)
  • Original study: Screening for hypertensive disorders of pregnancy: US Preventive Services Task Force final recommendation statement [10]
  • Related AMBOSS articles: Hypertensive Schwangerschaftserkrankungen | Vorsorgeuntersuchungen in der Schwangerschaft

Buprenorphine in the fentanyl era

One-Minute Telegram 84-2023-2/3

10-second takeaway

While buprenorphine is an effective treatment for opioid use disorder (OUD), the current recommended maintenance dose of 16 mg/day may not be adequate for individuals who use fentanyl, which is now the leading cause of opioid-related overdose death in the US. In this study, higher doses of buprenorphine were associated with greater OUD treatment retention in a setting where recreational use of fentanyl is widespread. Further research is necessary to determine if higher doses of buprenorphine should be given to individuals who use fentanyl to better mitigate opioid withdrawal symptoms and cravings.

Study breakdown

  • Study population: 6499 adults (61% male; 57% aged 25–44 years) starting a sublingual buprenorphine formulation for OUD treatment for the first time
  • Methods: retrospective cohort study
    • Data was extracted from the Rhode Island Prescription Drug Monitoring Program.
    • Exposure: daily buprenorphine dose; primary analysis compared buprenorphine 16 mg and 24 mg; exploratory analyses included 8 mg
    • Participants were monitored using prescription fill dates and days’ supply.
    • Primary outcome: time to buprenorphine discontinuation
    • Follow-up: 180 days
  • Main results
    • Treatment discontinuation was higher in participants prescribed buprenorphine 16 mg than in those prescribed buprenorphine 24 mg daily.
      • 59% vs. 53% (P = 0.005)
      • Adjusted HR, 1.20 (95% CI, 1.06–1.37)
    • Time to treatment discontinuation was similar in participants prescribed buprenorphine 8 mg and 16 mg daily.
  • Limitations include:
    • Results may have been influenced by unmeasured confounders given the retrospective study design.
    • Not generalizable to individuals taking daily buprenorphine doses higher than 24 mg or other buprenorphine formulations, or those treated in health care settings other than outpatient settings
    • Further research is needed on the risks and benefits of buprenorphine doses higher than 24 mg.
  • Study funding: National Institute on Drug Abuse
  • Original study: Buprenorphine dose and time to discontinuation among patients with opioid use disorder in the era of fentanyl [11]
  • Related AMBOSS articles: Opioide (Intoxikation und Abhängigkeit) | Substitutionsbehandlung bei Opioidabhängikeit | Akute Opioidintoxikation

A STEP in the right direction for obesity-related HFpEF

One-Minute Telegram 84-2023-3/3

10-second takeaway

Individuals with heart failure with preserved ejection fraction (HFpEF) and obesity experience more severe functional impairment and heart failure (HF) symptoms than those with HFpEF without obesity. In this study, the use of semaglutide resulted in reduced HF-related symptoms, enhanced physical functionality, and significant weight loss compared to placebo. These findings suggest that treatments such as semaglutide may meaningfully improve outcomes for patients with obesity and HFpEF.

Study breakdown

  • Study population: 529 adults (mean age 69 years; 56% female; 96% White) with LVEF ≥ 45%, NYHA class II–IV, and BMI ≥ 30 kg/m2
  • Methods: international, randomized, double-blind, placebo-controlled trial (STEP-HFpEF trial)
    • Randomized 1:1 to receive once-weekly semaglutide (starting dose 0.25 mg for 4 weeks, titrated to 2.4 mg by week 16) or placebo for 52 weeks
    • Stratified by BMI: < 35 or ≥ 35 kg/m2
    • No participants underwent bariatric surgery, but some received other weight-loss treatments.
    • Primary endpoints
      • Change in HF-related symptoms, physical function, QoL, and social function (based on a cardiomyopathy questionnaire)
      • Change in body weight
    • Follow-up: 5 weeks after end of treatment (i.e., week 57)
  • Main results
    • Compared to the placebo group, participants in the semaglutide group had:
      • A greater improvement in HF-related symptoms, physical function, QoL, and social function
      • Greater weight loss: -13.3% vs. -2.6% total body weight (estimated difference, -10.7 percentage points; 95% CI, -11.9 to -9.4)
      • Lower rate of serious adverse events (including cardiac events): 13.3% vs. 26.7%
    • The rate of treatment discontinuation due to serious adverse events was similar in both groups.
  • Limitations include:
    • Limited generalizability given the exclusion of individuals with:
      • > 5 kg change in body weight 90 days prior to screening
      • History of diabetes
    • White individuals were overrepresented in the study.
  • Study funding: Novo Nordisk
  • Original study: Semaglutide in patients with heart failure with preserved ejection fraction and obesity [12]
  • Related AMBOSS articles: HFpEF

Q3 2023toggle arrow icon

Edition 83 - September 23, 2023toggle arrow icon

Hormonal contraception and NSAIDs: a risky tango

One-Minute Telegram 83-2023-1/3

10-second takeaway

Hormonal contraceptives and nonsteroidal antiinflammatory drugs (NSAIDs) independently increase the risk of venous thromboembolism (VTE), but the risk with concomitant use is not well studied. In this national cohort study, the adjusted incidence rate ratio (AIRR) of VTE in women aged 15–49 years was higher in those who used NSAIDs than in those who did not; the incidence was highest in women with concomitant use of NSAIDs and medium- or high-risk hormonal contraception. Women using both NSAIDs and hormonal contraception should be advised about the increased risk of VTE.

Study breakdown

  • Study population: all women aged 15–49 years living in Denmark between 1996 and 2017 without a history of venous or arterial thrombotic events, cancer, thrombophilia, hysterectomy, oophorectomy, sterilization, or infertility treatment (∼ 2 million)
  • Methods: nationwide historical cohort study
    • Information was obtained from national registries.
    • Timing and duration of nonaspirin NSAID and hormonal contraceptive use was derived from filled prescription data.
    • Based on current understanding, hormonal contraceptives were classified according to VTE risk: high, medium, or low/no risk.
    • Primary outcome: first diagnosis of lower extremity deep venous thrombosis or pulmonary embolism
    • Follow-up: median of 10 years
  • Main results
    • The AIRR of VTE was highest with concomitant use of NSAIDs and higher-risk hormonal contraception.
    • No use of NSAIDs or hormonal contraception: AIRR = 1.0 (reference)
    • NSAID use only: 7.2 (95% CI, 6.0–8.5)
    • Hormonal contraceptive use only
      • Low or no risk: 1.1 (1.0–1.2)
      • Medium risk: 3.0 (2.8–3.2)
      • High risk: 4.1 (3.9–4.3)
    • Concomitant use
      • NSAIDs + low or no risk: 4.9 (2.8–8.7)
      • NSAIDs + medium risk: 23.4 (17.6–31.1)
      • NSAIDs + high risk: 44.8 (39.2–51.3)
  • Limitations include:
    • Determination of NSAID and contraceptive use was based on filled prescriptions rather than direct observation.
    • Some potential confounders (e.g., smoking, obesity) were not adjusted for.
    • Results may not be generalizable to patients from groups that are underrepresented in the Danish population.
  • Study funding: Danish Heart Foundation
  • Original study: Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study [13]
  • Related AMBOSS articles: Phlebothrombose | Lungenembolie

The OPTIMAL-BP after endovascular thrombectomy for stroke

One-Minute Telegram 83-2023-2/3

10-second takeaway

Current guidelines recommend maintaining systolic blood pressure (SBP) under 180 mm Hg after successful endovascular thrombectomy (EVT) for acute ischemic stroke (AIS), but optimal SBP targets for decreasing the risk of intracerebral hemorrhage (ICH) and cerebral edema remain unknown. This trial found that intensive blood pressure control during the initial 24 hours after successful EVT for AIS led to worse functional outcomes at 3 months compared to conventional management. Conventional management remains the preferred strategy following EVT for AIS.

Study breakdown

  • Study population: 306 South Korean adults aged ≥ 20 years (mean age 73 years; 40% women) with an AIS caused by large vessel occlusion who underwent successful reperfusion with EVT and had SBP ≥ 140 mm Hg within 2 hours after the procedure
  • Methods: multicenter, prospective, randomized, open-label, blinded end-point clinical trial (OPTIMAL-BP trial)
    • Randomized 1:1 to intensive management (SBP target < 140 mm Hg) or conventional management (SBP target 140–180 mm Hg) for 24 hours after reperfusion
    • Noninvasive SBP was continuously monitored.
    • Nicardipine was the preferred antihypertensive (other medications could be used at the physician’s discretion).
    • In the conventional management group, vasopressors were not used to maintain SBP ≥ 140 mm Hg but IV fluids and/or inotropes could be used to treat clinically significant hypotension.
    • Neuroimaging was performed after 24 hours or if neurological symptoms worsened.
    • Primary outcome: functional independence at 3 months
    • Primary safety outcomes
      • Symptomatic ICH within 36 hours
      • Death related to the index stroke within 3 months
    • Secondary outcomes included occurrence of malignant brain edema within 36 hours.
  • Main results
    • The trial was terminated early because of safety concerns in the intensive management group.
    • Functional independence at 3 months was significantly lower with intensive management than with conventional management: 39% vs. 54% (risk difference, -15.1%; 95% CI, -26.2% to -3.9%).
    • Malignant brain edema occurred more frequently with intensive management than conventional management: adjusted OR, 7.88 (1.57 to 39.39).
    • Rates of death and symptomatic ICH were similar in both groups.
  • Limitations include:
    • Potential selection bias given that < 20% of screened patients were randomized
    • The trial was terminated early, which may have limited the statistical power.
    • Limited generalizability
      • Conducted in South Korea only
      • Multiple exclusion criteria, e.g., prestroke disability, serious comorbidities
  • Study funding: Ministry of Health and Welfare, Republic of Korea
  • Original study: Intensive vs conventional blood pressure lowering after endovascular thrombectomy in acute ischemic stroke: the OPTIMAL-BP randomized clinical trial [14]
  • Related AMBOSS article: Ischämischer Schlaganfall

Older adults benefit from complete revascularization after acute MI

One-Minute Telegram 83-2023-3/3

10-second takeaway

Complete revascularization using percutaneous coronary intervention (PCI) to treat nonculprit lesions is known to be beneficial in younger patients after an acute myocardial infarction (MI), but this approach is not well studied in older patients. In this trial, older patients who underwent physiology-guided complete revascularization had better outcomes than those who underwent culprit-only revascularization. Complete revascularization with PCI after an acute MI should not be withheld based on age alone.

Study breakdown

  • Study population: 1445 adults aged ≥ 75 years (median age 80 years, 37% women) with an acute MI (35% STEMI) who had successful PCI of the culprit lesion and had additional significant-appearing coronary artery disease
  • Methods: international (Italy, Spain, Poland), multicenter, randomized trial (FIRE trial)
    • Randomized 1:1 to physiology-guided complete revascularization or culprit lesion-only revascularization
    • Guideline-based medical therapy was used in both groups.
    • Primary outcome: composite of death, MI, stroke, or coronary revascularization for ischemia at 1 year
    • Secondary outcome: composite of cardiovascular death or MI
    • Safety outcome: composite of contrast-associated acute kidney injury, stroke, or bleeding
    • Follow-up: 1 year
  • Main results
    • Fewer outcome events were reported in the complete revascularization group than in the culprit-only group.
      • Primary outcome events: 15.7% vs. 21% (NNT = 19)
      • Secondary outcome events: 8.9% vs. 13.5% (NNT = 22)
    • The occurrence of individual components of the primary outcome (excluding stroke) was significantly lower in the complete revascularization group than in the culprit-only group.
    • Safety outcomes were similar in both groups.
  • Limitations include:
    • Nonblinded design
    • Generalizability to treatments that do not utilize sirolimus-eluting stents is limited.
    • Patients with the following were excluded:
      • Culprit coronary artery not clearly identified
      • Nonculprit lesion in the left main coronary artery
      • Planned or previous surgical revascularization
      • Life expectancy < 1 year
  • Study funding: Sahajanand Medical Technologies, Medis Medical Imaging Systems, Eukon, Siemens Healthineers, General Electric Healthcare, and Insight Lifetech
  • Original study: Complete or culprit-only PCI in older patients with myocardial infarction [15]
  • Related AMBOSS article: Akutes Koronarsyndrom

Edition 82 - September 9, 2023toggle arrow icon

Protect with PrEP

One-Minute Telegram 82-2023-1/3

10-second takeaway

HIV affects over one million individuals in the US. The United States Preventive Services Task Force (USPSTF) has reaffirmed its previous recommendation to offer preexposure prophylaxis (PrEP) to individuals at increased risk of HIV acquisition and added evidence for the efficacy of newer PrEP formulations. The use of PrEP should be based on shared decision-making between the patient and the prescribing clinician.

Recommendation breakdown

  • Recommendation: The USPSTF concluded with high certainty that there is a substantial benefit to using PrEP to decrease the risk of acquiring HIV in individuals at increased risk.
  • Applicable population
    • Sexually active HIV-negative adolescents and adults with any of the following:
      • A sexual partner with HIV
      • A recent history of bacterial STI
      • Condomless sex with partners whose HIV status is unknown
      • High-risk practices (e.g., sex work)
    • HIV-negative persons who inject drugs and share drug-injection equipment with a partner who is HIV-positive or who shares injection equipment with others
  • Additional information
    • Acute and chronic HIV must be ruled out prior to initiating PrEP.
    • Other recommended pre-PrEP assessments include:
      • Pregnancy testing
      • STI screening
      • Kidney function testing
      • Hepatitis B serology
      • Lipid profile testing
    • Tenofovir-based oral formulations and injectable cabotegravir are FDA-approved for PrEP in individuals weighing ≥ 35 kg (77 lbs).
    • Continued condom use is recommended, as the time from initiation of PrEP to full protection from HIV is unknown and PrEP does not provide protection from other STIs.
  • Potential harms of PrEP use include:
  • Limitations include:
    • The USPSTF does not offer recommendations regarding PrEP in persons weighing < 35 kg (77 lbs).
    • While the FDA has approved the use of tenofovir disoproxil fumarate/emtricitabine for PrEP in pregnant individuals, data regarding its safety and efficacy during pregnancy and breastfeeding is limited.
    • Further research is needed on:
      • Validated tools to identify individuals at risk
      • Long-term safety and efficacy of PrEP in pregnancy and adolescence
  • Study funding: Agency for Healthcare Research and Quality (AHRQ)
  • Original study: Preexposure prophylaxis to prevent acquisition of HIV [16]
  • Related AMBOSS article: HIV-Infektion

Don’t trust, always verify: AI generates fake medical citations

One-Minute Telegram 82-2023-2/3

10-second takeaway

The use of artificial intelligence (AI) in medical education and research has the potential to improve efficiency, but the content it produces is not always reliable. This study found that ChatGPT cited fake journal articles and did not include the most recent developments. Although a chatbot may be a helpful tool, it has limitations and can generate unreliable information.

Study breakdown

  • Study purpose: to quantify OpenAI’s ChatGPT-3.5 and ChatGPT-4 citation error rate
  • Methods
    • GPT-3.5 and GPT-4 were used to generate discussion on topics relating to learning health systems (LHS) on both a general (e.g., LHS and data) and specific (e.g., creating a stroke risk prediction model) level. The chatbot was engaged with systematically ordered prompts comprising the following elements:
      • Topic context (e.g., “LHS vision will transform our health care systems.”)
      • Topic question (e.g., “What is LHS?”)
      • Request for references (e.g., “Provide some journal articles for LHS as a reference.”)
    • Each journal article cited by the chatbot was verified; if a citation could not be verified, it was considered fake.
  • Main results
    • 159/162 (98.1%) of citations provided by the GPT-3.5 model were found to be fake (95% CI, 94.7–99.6%).
    • 53/257 (20.6%) of citations provided by the GPT-4 model were found to be fake (95% CI, 15.8–26.1%).
    • Fake citations were more likely to be generated with specific discussions than general ones.
    • The chatbot did not provide information on the latest advances in LHS.
  • Limitations include: Since the study only tested topics related to LHS, the findings may not be generalizable to other areas of medical research.
  • Study funding: Unknown
  • Original study: Accuracy of chatbots in citing journal articles [17]
  • Related AMBOSS article: Studientypen der medizinischen Forschung

COX blocking to prevent unwanted pregnancy

One-Minute Telegram 82-2023-3/3

10-second takeaway

Levonorgestrel emergency contraception (EC) is used to prevent unwanted pregnancy, but is not effective if used after ovulation has occurred. In this trial, coadministration of levonorgestrel with piroxicam, a long-acting cyclooxygenase (COX) inhibitor, within 72 hours of unprotected sex prevented a higher proportion of pregnancies than expected based on an established model compared to levonorgestrel and placebo. Use of a COX inhibitor in combination with levonorgestrel may increase the efficacy of EC.

Study breakdown

  • Study population: 860 women aged ≥ 18 years (mean age 30 years) in Hong Kong who requested EC within 72 hours of unprotected sex
  • Methods: randomized, double-blind, placebo-controlled trial
    • Randomized 1:1 to levonorgestrel 1.5 mg plus piroxicam 40 mg PO once or levonorgestrel 1.5 mg plus placebo PO once
    • Primary outcome: proportion of pregnancies prevented compared to pregnancies expected
    • Secondary outcomes: pregnancy rate after EC, change in menstrual pattern, nonmenstrual bleeding, and other adverse events
    • Follow-up: 1–2 weeks after expected menstrual period
  • Main results
    • A greater proportion of expected pregnancies were prevented in the piroxicam group (94.7%) than in the placebo group (63.4%).
    • Pregnancy rate was 0.2% in the piroxicam group compared to 1.7% in the placebo group (OR, 0.20; 95% CI, 0.02–0.91).
    • Changes in menstrual pattern, nonmenstrual bleeding, and adverse effects were similar between groups.
    • The most common adverse events within the first 3 days included fatigue or weakness, nausea, and lower abdominal pain.
  • Limitations include:
    • Limited generalizability given multiple exclusion criteria, including:
      • Current or recent use of hormonal contraception or NSAIDs
      • > 1 episode of unprotected sex in the current menstrual cycle
      • Absence of menses after a recent abortion or during the postpartum period
      • Unknown last menstrual period date
      • Current use of certain medications (e.g., anticoagulants)
      • History of certain medical conditions (e.g., hypertension, urticaria)
    • Some groups were underrepresented in the study, including women with overweight, obesity, and/or a non-Chinese ethnicity, further limiting generalizability.
  • Study funding: None
  • Original study: Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial [18]
  • Related AMBOSS article: Orale Kontrazeptiva

Edition 81 - August 26, 2023toggle arrow icon

Swift lift for postpartum depression

One-Minute Telegram 81-2023-1/3

10-second takeaway

Postpartum depression (PPD) affects almost one in five new mothers, but it can take weeks to months for standard-of-care antidepressants to take effect. In this trial, oral zuranolone, a neuroactive steroid GABAA receptor modulator, was more effective than placebo in improving symptoms of PPD, with a median time to improvement of only 9 days. This is the first FDA-approved rapid-acting oral medication for the treatment of PPD.

Study breakdown

  • Study population
    • 196 adults aged 18–45 years with severe PPD
    • 70% White, 22% Black, 8% other; 38% Hispanic
  • Methods: phase 3 randomized, double-blind, placebo-controlled trial
    • Randomized 1:1 to zuranolone 50 mg PO or placebo daily for 14 days
    • The severity of depressive symptoms was measured at baseline and at days 3, 15, 28, and 45.
    • Primary efficacy endpoint: change in depression severity from baseline to day 15
    • Key secondary endpoints
      • Change in depression severity at days 3, 28, and 45
      • Median time to improvement
    • Safety and tolerability: Adverse effects and dropout rates were recorded.
    • Follow-up: 45 days
  • Main results
    • Participants in the zuranolone group had significant improvement of depressive symptoms compared to those in the placebo group at all measured time points.
    • Median time to symptom improvement: 9 days in the zuranolone group compared to 43 days in the placebo group
    • The most common adverse effects, reported in > 10% of participants, were somnolence, dizziness, and sedation.
    • One patient in the zuranolone group ended participation because of adverse effects.
  • Limitations include:
    • Individuals with a history of other psychiatric conditions were excluded.
    • Only individuals with severe PPD were included in the study.
  • Study funding: Sage Therapeutics and Biogen
  • Original study: Zuranolone for the treatment of postpartum depression [19]
  • Related AMBOSS article: Postpartale Depression | Unipolare Depression

Hypertension and the ill-fitting blood pressure cuff

One-Minute Telegram 81-2023-2/3

10-second takeaway

Accurate blood pressure (BP) measurement is required for optimal management of cardiovascular disease, but health care providers frequently use an inappropriately sized BP cuff when obtaining these measurements. In this study, using an automated BP device with a regular-size BP cuff rather than a specifically sized BP cuff resulted in inaccurate systolic blood pressure (SBP) measurements. Training medical staff on correct BP measurement procedures can improve patient care.

Study breakdown

  • Study population: 195 community-dwelling adults aged ≥ 18 years (mean age 54 years)
    • 66% female; 68% Black, 30% White; 3% Hispanic
    • 51% with hypertension; mean BMI 28.8 kg/m2
  • Methods: randomized crossover trial
    • The appropriate cuff size was determined using mid-upper arm circumference.
    • Participants had four sets of BP measurements with an automated device: two with an appropriately sized cuff, one with an undersized cuff, and one with an oversized cuff (each set included a measurement with a regular-size cuff, which could be appropriately or inappropriately sized, depending on the patient).
    • Primary outcome: difference in SBP obtained with a regular-size BP cuff compared to a specifically sized BP cuff
    • Secondary outcome: difference in SBP obtained with an oversized or undersized cuff compared to an appropriately sized BP cuff
  • Main results
    • The use of a regular-size BP cuff resulted in inaccurate SBP measurements if it did not fit appropriately.
      • Individuals who needed a small BP cuff: SBP was lower with a regular-size cuff than with a small cuff (mean SBP difference, -3.6 mm Hg; 95% CI, -5.6 to -1.7).
      • Individuals who needed a large or extra-large BP cuff: SBP was higher with a regular-size cuff than with a large (mean SBP difference, 4.8 mm Hg; 95% CI, 3.0 to 6.6) or extra-large BP cuff (mean SBP difference, 19.5 mm Hg; 95% CI, 16.1 to 22.9).
    • The difference between SBP obtained with an appropriately sized cuff and that obtained with an inappropriately sized one was greatest in those who required a large or extra-large BP cuff.
  • Limitations include:
    • The incidence of hypertension and obesity varied between the different groups, which may have led to confounding.
    • Findings are not generalizable to pregnant individuals, those with an arm circumference > 55 cm, or those with arteriovenous shunts in both arms.
  • Study funding: Resolve to Save Lives
  • Original study: Effects of cuff size on the accuracy of blood pressure readings: the cuff(SZ) randomized crossover trial [20]
  • Related AMBOSS article: Arterielle Hypertonie

Clearing the way: targeting amyloid plaques in Alzheimer disease

One-Minute Telegram 81-2023-3/3

10-second takeaway

Deposition of β-amyloid in the brain is an early finding in Alzheimer disease, and recent research has suggested that targeting the amyloid cascade with monoclonal antibodies may slow disease progression. In this phase 3 trial, donanemab significantly slowed Alzheimer disease progression and decreased brain amyloid plaque levels compared to placebo. Monoclonal antibody therapy may be a promising new treatment for symptomatic patients with early Alzheimer disease.

Study breakdown

  • Study population: 1736 adults aged 60–85 years (mean age 73 years) with early symptomatic Alzheimer disease and abnormal amyloid and tau pathology on PET imaging
    • 57% women; 92% White
    • 68% with low/medium tau pathology, 32% with high tau pathology
  • Methods: phase 3 multicenter, randomized, double-blind, parallel, placebo-controlled trial
    • Randomized 1:1 to IV donanemab (700 mg for the first 3 doses, then 1400 mg) or placebo every 4 weeks for 72 weeks
    • Groups were stratified by tau pathology level: low/medium or combined (low/medium and high).
    • Cognition and daily function were assessed using the integrated Alzheimer Disease Rating Scale (iADRS).
    • Imaging for amyloid monitoring was performed at 4, 12, 24, 52, and 76 weeks.
    • Primary outcome: change in iADRS score from baseline to week 76
    • Secondary outcomes included:
  • Main results
    • Disease progression was slower with donanemab than with placebo in both tau pathology populations.
      • 35% slower disease progression in the low/medium tau population (95% CI, 19.90–50.23%)
      • 22% slower disease progression in the combined tau population (95% CI, 11.38–33.15%)
    • There was a greater decrease in brain amyloid plaque levels in the donanemab group than in the placebo group.
    • The incidence of serious adverse events was higher in the donanemab group than in the placebo group.
      • Brain edema or effusion on planned imaging (24.0% vs. 2.1%)
      • Infusion-related reactions (8.7% vs. 0.5%)
      • Death (1.9% vs. 1.1%)
  • Limitations include:
    • Participants were predominantly White, limiting generalizability to other racial and ethnic groups.
    • Follow-up was limited to 76 weeks.
  • Study funding: Eli Lilly and Company
  • Original study: Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial [21]
  • Related AMBOSS articles: Morbus Alzheimer

Edition 80 - August 12, 2023toggle arrow icon

Pitavastatin to prevent CVD in HIV

One-Minute Telegram 80-2023-1/3

10-second takeaway

Individuals with HIV have an increased risk of cardiovascular disease (CVD), highlighting the importance of preventive lifestyle and pharmacological interventions to promote cardiac health. This study showed that, compared to placebo, pitavastatin, a statin that has minimal drug-drug interactions with antiretroviral therapy (ART), can reduce the risk of major adverse cardiovascular events (MACE) in individuals with HIV at low or moderate risk of CVD. Preventive statin therapy should be considered in individuals with HIV even if their risk of CVD is low or moderate.

Study breakdown

  • Study population: 7769 participants with well-controlled HIV on ART at low or moderate risk of cardiovascular disease; median age 50 years
  • Methods: phase 3 randomized placebo-controlled trial
    • Randomized 1:1 to pitavastatin 4 mg PO daily or placebo
    • Primary outcome: occurrence of MACE
    • Secondary outcomes
      • Composite of MACE and all-cause mortality
      • Safety events: myalgias, myopathies, diabetes, liver injury
    • Median follow-up: 5.1 years
  • Main results
    • The trial was terminated early because of proven effectiveness of the intervention.
      • Incidence of MACE was lower in the pitavastatin group than the placebo group (HR, 0.65; 95% CI, 0.48–0.90).
      • Composite of MACE and all-cause mortality was lower in the pitavastatin group than the placebo group (HR, 0.79; 0.65–0.96).
    • Incidence of muscle-related symptoms and diabetes mellitus were higher in the pitavastatin group than the placebo group, but discontinuation rate was low.
  • Limitations include: Early termination may have led to underestimation of long-term risks of pitavastatin use.
  • Study funding: National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, ViiV Healthcare
  • Original study: Pitavastatin to prevent cardiovascular disease in HIV infection [22]
  • Related AMBOSS articles: HIV-Infektion

Acute sinusitis: the color of nasal discharge is snot important

One-Minute Telegram 80-2023-2/3

10-second takeaway

Antibiotics are often overprescribed for children with upper respiratory tract symptoms and suspected acute sinusitis. This study demonstrated that antibiotics were more effective than placebo in reducing symptoms of acute sinusitis, but mainly when nasopharyngeal pathogens (NPP) were present. The effectiveness of antibiotics in reducing symptoms was similar in patients with clear or colored nasal discharge. Point-of-care testing for NPP may help reduce unnecessary antibiotic use.

Study breakdown

  • Study population: 515 children aged 2–11 (54% male, 52% White, 89% non-Hispanic) meeting established criteria for acute sinusitis
  • Methods: randomized clinical trial
    • Subgroups stratifed by presence or absence of green or yellow nasal discharge
    • NPP bacterial cultures obtained at beginning and end of study
    • Randomized 1:1 to a combination of amoxicillin 90 mg/kg/day and clavulanate 6.4 mg/kg/day PO or placebo
    • Primary outcome: daily symptom burden based on the Pediatric Rhinosinusitis Symptoms Scale (PRSS)
  • Main results
    • Mean PRSS scores were significantly lower in the antibiotic group than in the placebo group.
    • Median time to symptom resolution was lower in the antibiotic group (7 days) than in the placebo group (9 days).
    • Subgroup analysis
      • Mean PRSS score difference was greatest in the subgroup with culture-proven NPP.
      • Mean PRSS score difference was similar across groups regardless of nasal discharge color.
    • Higher incidence of diarrhea in antibiotic group than in placebo group: 11.4% vs. 4.7% (RR 2.40; 95% CI, 1.26–4.59)
  • Limitations include: limited generalizability to children with mild or severe sinusitis
    • Patients with severe sinusitis were excluded.
    • Study participants had higher PRSS scores than those who declined to participate.
  • Study funding: National Institute of Allergy and Infectious Diseases
  • Original study: Identifying children likely to benefit from antibiotics for acute sinusitis: a randomized clinical trial [23]
  • Related AMBOSS article: Sinusitis

The oral PEN is as mighty as the needle

One-Minute Telegram 80-2023-3/3

10-second takeaway

Fewer than 5% of patients whose medical record is flagged with a penicillin allergy label have a true penicillin allergy. This study demonstrated that a direct oral challenge in patients with a low-risk penicillin allergy was safe and noninferior to skin testing followed by an oral challenge in verifying an actual penicillin allergy. Direct oral penicillin testing could reduce the burden of proactive penicillin allergy delabeling and improve antibiotic stewardship.

Study breakdown

  • Study population: 377 adults with a reported penicillin allergy in their medical record and a PEN-FAST score of < 3
  • Methods: multicenter open-label, randomized clinical trial
    • PEN-FAST score (range 0–5) calculated based on:
      • Penicillin allergy reported
      • ≤ 5 years since reaction (2 points)
      • Angioedema or anaphylaxis OR severe cutaneous adverse reactions (2 points)
      • Treatment required (1 point)
    • Randomized 1:1 to direct oral penicillin challenge (intervention) or standard skin testing followed by oral challenge if the skin test was negative (control)
    • Primary outcome: immune-mediated reaction within one hour of oral challenge
    • Secondary outcomes: safety, delabeling possible
  • Main results
    • The oral penicillin challenge was positive in 0.5% of participants in both groups (RR 1.02; 90% CI, 0.10–10.34).
    • Adverse events within 5 days were similar between groups.
    • The penicillin allergy label was removed from 99.5% of participants records in the intervention group and from 97.9% in the control group.
  • Limitations include:
    • The majority of patients had a PEN-FAST score of < 2, limiting generalizability to patients with higher scores.
    • Patients with any history of drug-induced anaphylaxis were excluded, limiting generalizability regarding safety and noninferiority in that population.
  • Study funding: Austin Medical Research Foundation
  • Original study: Efficacy of a clinical decision rule to enable direct oral challenge in patients with low-risk penicillin allergy: the PALACE randomized clinical trial [24]
  • Related AMBOSS articles: Arzneimittelallergie | Penicilline

Edition 79 - July 29, 2023toggle arrow icon

Spill the T: testosterone safety in men with CVD

One-Minute Telegram 79-2023-1/3

10-second takeaway

Testosterone replacement therapy (TRT) is frequently used to treat symptoms of hypogonadism in men, but previous studies have provided conflicting information about its cardiovascular safety. In this large-scale study, TRT in men with preexisting or high risk of cardiovascular disease (CVD) was noninferior to placebo for the incidence of major adverse cardiac events (MACE), but was associated with a higher incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism. Because testosterone deficiency is not life-threatening, clinicians should continue to individualize the decision to begin TRT.

Study breakdown

  • Study population: 5204 men aged 45–80 years with preexisting or a high risk of CVD, symptoms of hypogonadism, and two morning testosterone levels < 300 ng/dL
  • Methods: noninferiority, multicenter, randomized, double-blind, placebo-controlled trial
    • Randomized 1:1 to daily transdermal 1.62% testosterone gel (TRT group) or placebo gel
    • The testosterone dose in the TRT group was adjusted to maintain a testosterone level between 350 and 750 ng/dL.
    • Primary endpoint: first MACE, i.e., death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke
    • Mean duration of treatment: 22 ± 14 months; mean follow-up: 33 ± 12 months
  • Main results
    • TRT was noninferior to placebo for incidence of MACE: 7.0% in the TRT group vs. 7.3% in the placebo group (HR, 0.96; 95% CI, 0.78–1.17)
    • The incidence of several adverse effects was higher in the TRT group than the placebo group.
  • Limitations include: Adherence and retention rates were low.
  • Study funding: AbbVie, Acerus Pharmaceuticals, Endo Pharmaceuticals, Upsher-Smith Laboratories
  • Original study: Cardiovascular safety of testosterone-replacement therapy [25]
  • Related AMBOSS article: Atherosklerose und kardiovaskuläre Prävention | Testosteronsubstitution

Does vitamin D supplementation reduce cardiovascular risk?

One-Minute Telegram 79-2023-2/3

10-second takeaway

Low serum vitamin D levels are associated with increased risk of cardiovascular disease, but studies to date have not shown that vitamin D supplementation prevents major adverse cardiovascular events (MACE). In this Australian study, 5 years of vitamin D supplementation was associated with a small reduction in the incidence of MACE compared to placebo, but the absolute risk difference was not significant. Further studies focusing on individuals with high cardiovascular risk may find a clearer role for vitamin D supplementation.

Study breakdown

  • Study population: 21,315 participants aged 60–84 years with no prior vitamin D supplementation and no contraindications to vitamin D therapy
  • Methods: randomized, double-blind, placebo-controlled trial
    • Randomized 1:1 to oral vitamin D3 60,000 IU/month or placebo
    • Main outcome: first MACE, i.e., myocardial infarction, stroke, or coronary revascularization
    • Incidence of MACE was determined using national administrative databases.
    • Serum 25(OH)D concentration was measured yearly in a random subset of participants.
    • Median treatment duration: 5 years
  • Main results
    • Vitamin D group had a slightly lower incidence of MACE than the placebo group: HR, 0.91; 95% CI, 0.81–1.01 (-5.8 events per 1000 participants)
      • Myocardial infarction: HR, 0.81; 0.67–0.98
      • Coronary revascularisation: HR, 0.89; 0.78–1.01
      • MACE in subgroup taking cardiovascular drugs: HR, 0.84; 0.74–0.97
    • Mean serum 25(OH)D concentration
  • Limitations include:
    • Angina and myocardial infarction are reported together in the national database, which may have affected the results.
    • The study population had lower statin usage and a lower smoking rate than the general population, limiting generalizability.
    • The results are not generalizable to populations with a greater prevalence of vitamin D deficiency.
  • Study funding: National Health and Medical Research Council
  • Original study: Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial [26]
  • Related AMBOSS articles: Atherosklerose und kardiovaskuläre Prävention | Vitamin-D-Mangel

Revisiting an old drug for smoking cessation

One-Minute Telegram 79-2023-3/3

10-second takeaway

Cytisinicline has been used successfully as an over-the-counter smoking cessation medication in Europe for over 50 years, but the current 6 times daily dosing regimen limits adherence. In this US study, individuals taking cytisinicline 3 times daily were significantly more likely to have continuous smoking abstinence than those taking placebo. This effective and well-tolerated medication may provide another option for treating nicotine dependence.

Study breakdown

  • Study population: 810 adults who smoked ≥ 10 cigarettes per day (mean age 53 years; 55% female; mean 19 cigarettes smoked daily)
  • Methods: double-blind, placebo-controlled, randomized trial
    • Randomized 1:1:1
      • Cytisinicline 3 mg 3 times daily for 12 weeks
      • Cytisinicline 3 mg 3 times daily for 6 weeks then placebo 3 times daily for 6 weeks
      • Placebo 3 times daily for 12 weeks
    • All participants received frequent behavioral support.
    • Assessments were conducted weekly from weeks 2 to 12 and at weeks 16, 20, and 24.
    • Abstinence was self-reported and verified by expired CO measurements (≤ 10 ppm).
    • Main outcomes
      • Continuous smoking abstinence during the last 4 weeks of active treatment
      • Continuous smoking abstinence from the end of treatment through week 24
  • Main results
    • Continuous smoking abstinence rates were significantly higher with cytisinicline than placebo.
      • 6-week course of cytisinicline
        • Weeks 3–6: 25.3% vs. 4.4% (OR, 8.0; 95% CI, 3.9–16.3)
        • Weeks 3–24: 8.9% vs. 2.6% (OR, 3.7; 1.5–10.2)
      • 12-week course of cytisinicline
        • Weeks 9–12: 32.6% vs. 7.0% (OR, 6.3; 3.7–11.6)
        • Weeks 9–24: 21.1% vs. 4.8% (OR, 5.3; 2.8–11.1)
    • Cytisinicline was well tolerated.
      • Nausea, abnormal dreams, and/or insomnia occurred in < 10% of participants.
      • No serious adverse events occurred.
  • Limitations include:
    • The study population was predominantly White, limiting generalizability to other racial and ethnic groups.
    • Individuals with mental health conditions and/or illicit drug use were excluded.
    • Follow-up was limited to 24 weeks; long-term results are unknown.
  • Study funding: Achieve Life Sciences pharmaceuticals
  • Original study: Cytisinicline for smoking cessation: a randomized clinical trial [27]
  • Related AMBOSS articles: Raucherentwöhnung

Edition 78 - July 15, 2023toggle arrow icon

USPSTF recommends screening adults for major depressive disorder and anxiety disorders

One-Minute Telegram 78-2023-1/3

10-second takeaway

Major depressive disorder (MDD) and anxiety disorders are common conditions with a potential to profoundly impact the well-being of affected individuals. The United States Preventive Services Task Force (USPSTF) has reaffirmed its previous recommendation to screen all adults for MDD and added a new recommendation to screen adults under 64 years of age for anxiety disorder. There was insufficient evidence to support a recommendation to screen for risk of suicide. Medical providers should use their clinical judgment to determine screening intervals.

Recommendation breakdown

  • Recommendations
    • The USPSTF concluded with moderate certainty that there is a benefit to screen for MDD in all adults and for anxiety disorders in adults < 64 years.
    • There was insufficient evidence to recommend screening for:
      • Anxiety disorders in adults ≥ 65 years
      • Risk of suicide in adults
  • Applicable population: asymptomatic adults ≥ 19 years, including pregnant and postpartum individuals
  • Additional information
    • Commonly used screening tests for depression included the Patient Health Questionnaire (PHQ) and Geriatric Depression Scale (GDS).
    • Commonly used screening tools for anxiety included versions of the Generalized Anxiety Disorder (GAD) Scale.
  • Potential harms of screening
    • Treatment of newly diagnosed anxiety disorders may result in addiction and/or misuse of benzodiazepines.
    • Some interventions for elevated risk of suicide may increase the risk for self-harm.
  • Limitations include:
    • There is limited data for recommendations on screening intervals for anxiety disorders and MDD.
    • The recommendations do not apply to depressive disorders other than MDD.
    • Further research is needed on:
      • Screening tools for anxiety disorders in specific populations
      • Benefits of screening for risk of suicide
  • Study funding: The Agency for Healthcare Research and Quality (AHRQ)
  • Original studies
    • Screening for anxiety disorders in adults [28]
    • Screening for depression and suicide risk in adults [29]

Promising potential for a once-weekly basal insulin analogue

One-Minute Telegram 78-2023-2/3

10-second takeaway

Daily basal insulin is often included in the treatment regimen of newly diagnosed type 2 diabetes in order to improve glycemic control, but the requirement of frequent injections may reduce patient adherence and actually worsen control. In this trial, an investigational once-weekly basal insulin analogue (insulin icodec) produced better glycemic control than once-daily insulin glargine in newly diagnosed type 2 diabetes. New longer-acting basal insulin analogues may improve glycemic control and potentially improve patient adherence by reducing the frequency of injections.

Study breakdown

  • Study population: 984 adults ≥ 18 years with type 2 diabetes, HbA1c 7–11%, BMI ≤ 40 kg/m2, and no previous history of insulin use
  • Methods
    • International, randomized, open-label, treat-to-target, phase 3a trial (ONWARDS 1)
    • Randomized 1:1 to receive once-weekly insulin icodec (starting dose 70 units per week) or once-daily insulin glargine U100 (starting dose 10 units per day)
    • Dosage was titrated to achieve a prebreakfast blood glucose level of 80–130 mg/dL.
    • Primary endpoint: change in HbA1c from baseline to 52 weeks
    • Secondary endpoint: percentage of time spent in target glycemic range of 70–180 mg/dL during weeks 48–52
    • Duration: 52-week main phase and 26-week extension
    • Follow-up period: 5 weeks
  • Main results
    • Mean reduction in HbA1c was greater in the insulin icodec group than in the glargine U100 group (estimated treatment difference, -0.19 percentage points; 95% CI, -0.36 to -0.03).
    • Percentage of time spent in the target glycemic range was higher in the insulin icodec group than in the glargine U100 group (estimated treatment difference, 4.27 percentage points; 95% CI, 1.92 to 6.62).
    • Participants in the insulin icodec group were more likely to have the following compared to those in the glargine U100 group:
      • Sustained decrease in HbA1c level at 78 weeks
      • HbA1c level of < 7% at 52 and 78 weeks
      • Increased time spent in the glycemic target range at 74–78 weeks
    • Incidence of hypoglycemia and adverse events were similar in both groups.
  • Limitations include:
    • Nonblinded design
    • Continuous glucose monitoring was not maintained throughout the entire trial.
    • Blinding of glucose measurements may have limited titration of doses and increased the risk of hypoglycemia episodes.
  • Study funding: Novo Nordisk
  • Original study: Weekly icodec versus daily glargine U100 in type 2 diabetes without previous insulin [30]

Is bempedoic acid an effective alternative for patients with statin intolerance?

One-Minute Telegram 78-2023-3/3

10-second takeaway

Statins are recommended for the primary prevention of major adverse cardiovascular events (MACE), but there are no known effective alternatives for treating at-risk individuals with statin intolerance. In this trial, bempedoic acid was shown to reduce the risk of first-time MACE in at-risk patients with statin intolerance. Bempedoic acid may be an effective alternative to statins for primary prevention of MACE.

Study breakdown

  • Study population: 4206 adults (mean age 68 years) with LDL-C ≥ 100 mg/dL, high cardiovascular risk, no previous MACE, and a reported statin intolerance (59% female; 92% White, 3% Black; 66% with diabetes)
  • Methods: international, masked, randomized clinical trial
    • 1:1 randomization to bempedoic acid (180 mg PO daily) or placebo
    • LDL-C values were unmasked at month 6 and treatment was adjusted per local protocol if they were ≥ 25% above baseline.
    • High-sensitivity C-reactive protein (hsCRP) was measured at month 12.
    • Primary endpoint: time to first occurrence of 4-component MACE (death from a cardiovascular cause, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization)
    • Secondary endpoints
      • Time to first occurrence of a 3-component MACE (death from a cardiovascular cause, nonfatal myocardial infarction, nonfatal stroke)
      • Time to first occurrence of a 5-component MACE (death from a cardiovascular cause, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina)
    • Other outcomes: all-cause mortality
    • Median follow-up: 39.9 months
  • Main results
    • Risk of MACE was reduced in the bempedoic group vs. the placebo group
      • 4-component MACE: 5.3% vs. 7.6% (adjusted HR, 0.70; 95% CI, 0.55–0.89)
      • 3-component MACE: 4.0% vs. 6.4% (HR, 0.64; 95% CI, 0.48–0.84)
      • 5-component MACE: 2.3% vs. 7.8% (HR, 0.69; 95% CI, 0.54–0.88)
    • All-cause mortality was lower in the bempedoic group than in the placebo group.
    • LDL-C and hsCRP levels were lower in the bempedoic acid group than in the placebo group.
    • Incidence of serious adverse events and adverse events leading to drug discontinuation were similar between groups.
  • Limitations include:
    • The study is a subgroup analysis of a larger trial, which may have caused an increase in false-positive results and wider confidence intervals.
    • The study did not include participants with LDL-C levels < 100 mg/dL.
  • Study funding: Esperion Therapeutics, Inc.
  • Original study: Bempedoic acid for primary prevention of cardiovascular events in statin-intolerant patients [31]

Edition 77 - July 1, 2023toggle arrow icon

The drill still fits the bill for chronic SDH

One-Minute Telegram 77-2023-1/3

10-second takeaway

Burr-hole craniostomy is the current standard of care for symptomatic chronic subdural hematoma (SDH), but noncontrolled studies have suggested that glucocorticoid therapy may be an effective alternative. In this trial, patients with symptomatic chronic SDH treated with standalone dexamethasone had worse outcomes and more complications than patients treated with surgery.

Study breakdown

  • Study population: 252 adults (mean age 74 years; 77.4% men) with a new diagnosis of symptomatic chronic SDH verified by CT scan
  • Methods: multicenter, open-label, controlled noninferiority trial in the Netherlands
    • Randomized 1:1 to 19-day taper of oral or IV dexamethasone (n = 127) vs. burr-hole evacuation with subdural drain (n = 125)
    • Dexamethasone was discontinued and surgery was offered if participants did not show functional improvement at 2 weeks or had worsening symptoms, severe adverse effects, or hematoma expansion.
    • Primary endpoint: functional outcome at 3 months (modified Rankin scale)
    • Secondary endpoints: additional therapy received, length of hospitalization, adverse events
  • Main results
    • The trial was terminated prematurely because of poor outcomes and adverse events in the dexamethasone group.
    • Dexamethasone did not meet noninferiority criteria: adjusted OR, 0.55 (95% CI, 0.34–0.90) for better functional outcomes compared with surgery
    • Compared with the surgery group, the dexamethasone group:
    • Received more additional therapies (61% vs.17%)
    • Had longer mean hospitalizations (12 days vs. 7 days)
    • Had more adverse events: infection (23% vs.19%), hyperglycemia (20% vs. 4%), delirium (16% vs. 6%)
  • Limitations include:
    • Open-label design and local practice patterns may have influenced the decision to perform surgery on patients in the dexamethasone group.
    • Results may not be generalizable: Only ∼ 25% of screened patients with SDH were enrolled.
    • Most patients had mild symptoms.
    • Multiple exclusion criteria (e.g., coma, lack of symptoms, HbA1c > 8%)
    • The dexamethasone group had worse functional impairment at baseline, which may have contributed to negative outcomes.
  • Study funding: Netherlands Organization for Health Research and Development; Jacobus Foundation, the Hague; and Erasmus Medical Center
  • Original study: Dexamethasone versus surgery for chronic subdural hematoma [32]
  • Related AMBOSS article: Subdurales Hämatom

DOACs safe and effective in cancer-associated VTE

One-Minute Telegram 77-2023-2/3

10-second takeaway

Current guidelines recommend the use of low molecular weight heparin (LMWH) to prevent recurrent venous thromboembolism (VTE) in patients with cancer. This trial demonstrated that direct oral anticoagulants (DOACs) were noninferior to LMWH in the prevention of recurrent VTE in patients with cancer. DOACs are likely a safe and convenient alternative to LMWH for patients with cancer-associated VTE.

Study breakdown

  • Study population: 671 adults with cancer and a recently diagnosed VTE
    • 55% female; 83% White, 12% Black, 5% Hispanic or Latino
    • Cancers included solid tumors, lymphoma, chronic lymphocytic leukemia, and multiple myeloma
    • Patients with platelets ≥ 50,000/mcL, eGFR ≥ 15 mL/min/1.73 m2, and/or life expectancy ≥ 3 months were excluded.
  • Methods: multicenter, randomized, nonblinded pragmatic effectiveness study
    • Randomized 1:1 to a DOAC (n = 335) or LMWH (n = 336) for 6 months
    • Specific agents were chosen based on individual patient factors and availability.
    • Primary outcome: cumulative recurrence of nonfatal VTE at 6 months
    • Other outcomes: bleeding, death, health-related quality of life, patient perception of anticoagulation therapy, serious and severe adverse events, adherence
  • Main results
    • No significant difference in recurrent VTE rate in the DOAC group (6.1%) vs. the LMWH group (8.8%): difference less than the predefined 3% noninferiority margin
    • Agents received
    • DOAC group: 58% apixaban, 37% rivaroxaban, 3% dabigatran, 2% edoxaban
    • LMWH group: 90% enoxaparin, 7% fondaparinux, 3% dalteparin
    • No significant difference in major bleeding, death, or patient-reported outcomes
    • Higher adherence in the DOAC group at 6 months (71% vs. 59%)
  • Limitations include:
    • Patients and their treating physicians were nonblinded.
    • Some participants were already receiving anticoagulation before randomization.
    • Potential bias toward DOAC efficacy due to lower adherence to LMWH
    • The predominantly White study population limits generalizability to other groups.
  • Study funding: Patient-Centered Outcomes Research Institute
  • Original study: Direct oral anticoagulants vs low-molecular-weight heparin and recurrent VTE in patients with cancer: a randomized clinical trial [33]
  • Related AMBOSS article: Tiefe Beinvenenthrombose

Nitro patch is no match for the hot flash

One-Minute Telegram 77-2023-3/3

10-second takeaway

Concern about the safety of long-term hormone therapy for perimenopausal symptoms has led to increased interest in nonhormonal treatments for hot flashes. In this study, continuous transdermal nitroglycerin (NTG) therapy did not significantly decrease the frequency or severity of hot flashes compared to placebo. Further research into other approaches to reducing perimenopausal vasomotor symptoms is needed.

Study breakdown

  • Study population: 141 perimenopausal and postmenopausal women (age range 40–62 years) with ≥ 7 hot flashes per day who were not receiving other medications with potential efficacy for hot flashes
  • Methods: single-center, double-blinded, placebo-controlled RCT
    • Randomized 1:1 to uninterrupted transdermal NTG (0.2–0.6 mg/hour daily; n = 70) vs. placebo patch (n = 71) for 12 weeks
    • Primary outcome: change in frequency of hot flashes at 5 and 12 weeks
    • Other outcomes: change in frequency of moderate to severe hot flashes, hot flash severity, impact on function and quality of life, safety (headaches, chest pain, syncope, blood pressure)
  • Main results
    • No significant difference in primary outcome between groups
    • Both groups reported a reduction in frequency of all hot flashes and moderate to severe hot flashes.
    • The NTG subgroup in late perimenopause had a reduction in moderate to severe hot flash frequency compared to placebo (difference -3.0 episodes per day; 95% CI, -5.2 to -0.2).
    • Significantly more headaches with NTG at 1 week (66% vs. 6%) but not at 12 weeks (1.4% vs. 1.4%)
  • Limitations include:
    • Higher rate of medication discontinuation in the NTG group (20% vs. 7%)
    • Racial heterogeneity: more Black participants in the NTG group (17% vs. 6%)
  • Study funding: National Institutes of Health
  • Original study: Efficacy of continuous transdermal nitroglycerin for treating hot flashes by inducing nitrate cross-tolerance in perimenopausal and postmenopausal women: a randomized clinical trial [34]
  • Related AMBOSS article: Menopause

Q2 2023toggle arrow icon

Edition 76 - June 3, 2023toggle arrow icon

Missed opportunities in the treatment of OUD

One-Minute Telegram 76-2023-1/3

10-second takeaway

Mortality related to opioid use disorder (OUD) is increasing rapidly in the United States, particularly in the Black population. In this study, Black patients were substantially less likely to receive outpatient pharmacological intervention for OUD than White patients. Addressing racial and ethnic disparities in the treatment of OUD is necessary to successfully combat the national opioid overdose epidemic.

Study breakdown

  • Study population: 23,370 adults receiving Medicare as a result of disability who experienced at least one OUD-related index event (15% Black, 8% Hispanic, 77% White)
  • Methods: retrospective cohort study using Medicare claims data from 2016 to 2019
    • OUD-related index events included:
      • Emergency department or inpatient treatment for a nonfatal overdose
      • Hospitalization with an injection drug use-related infection
      • Admission to an OUD rehabilitation facility or detoxification unit
    • Patients with long-term opioid prescriptions and those receiving end-of-life care were excluded.
    • Primary outcome: receipt of buprenorphine, naltrexone, or naloxone within 180 days of an OUD index event
    • Secondary outcomes: contact with a health care provider within 180 days of an index event
  • Main results
    • Black individuals (12.7%) were less likely to receive buprenorphine following an OUD event than Hispanic (18.7%) or White individuals (23.3%).
    • Black individuals (14.4%) were less likely to receive naloxone following an OUD event than Hispanic (20.7%) or White individuals (22.9%).
    • Naltrexone receipt was low overall and did not differ between groups.
    • Racial differences in receipt of medications did not change significantly from 2016 to 2019.
    • Disparities in opportunities to receive medication after an OUD event were minor (mean number of ambulatory visits within 180 days: 6.6 for Black patients, 6.7 for Hispanic patients, and 7.6 for White patients).
  • Limitations include:
    • Receipt of methadone following an OUD event was not included in the study, which may have led to confounding.
    • Claims data only reflects prescriptions that were filled.
    • The study only included Medicare beneficiaries with disabilities and therefore may not be generalizable to other populations.
  • Study funding: National Institute on Drug Abuse, National Institute on Aging
  • Original study: Racial inequality in receipt of medications for opioid use disorder [35]
  • Related AMBOSS articles: Opioidabhängigkeit | Opioid-Intoxikation | Opioidentwöhnung

Hypertrophic hearts can still flex

One-Minute Telegram 76-2023-2/3

10-second takeaway

Health care providers often instruct patients with hypertrophic cardiomyopathy (HCM) to avoid vigorous exercise to reduce the risk of sudden cardiac death, but evidence for this recommendation is lacking. In this study, patients with HCM who exercised vigorously on a regular basis were no more likely to experience sudden cardiac death or a life-threatening arrhythmia than those who engaged in moderate exercise or were sedentary. Shared decision-making should be used to determine the appropriate activity level for patients with HCM, balancing the low risk of sudden cardiac death with the overall benefits of an active lifestyle.

Study breakdown

  • Study population: 1660 individuals with HCM (either phenotype positive, or phenotype negative and genotype positive) aged 8–60 years (mean age 39 years; 60% male) who were able to exercise
  • Methods: investigator-initiated, international, multicenter, prospective, observational cohort study
    • Patients were recruited from high-volume HCM centers or self-enrolled
    • Exposure: self-reported activity levels (based on a validated online questionnaire)
      • Vigorous: ≥ 6 MET intensity for ≥ 60 hours a year (n = 699)
      • Moderate: 4–5.9 MET intensity for ≥ 60 hours a year (n = 709)
      • Sedentary: < 4 MET intensity and/or < 60 hours a year (n = 252)
    • Outcome: composite endpoint of death, resuscitated sudden cardiac arrest, syncope due to arrhythmia, and appropriate implantable cardioverter defibrillator shocks (based on medical record data)
    • Follow-up period: 3 years
  • Main results
    • 4.6% of participants experienced the composite endpoint
    • No significant difference between rates of the composite endpoint in participants engaging in vigorous exercise (4.7%) and those engaging in nonvigorous (moderate or sedentary) activity (4.6%): adjusted HR, 1.01; 95% one-sided CI, 1.48 (below prespecified boundary of 1.5 for noninferiority)
    • Results were similar in a post hoc analysis including only phenotype-positive patients.
  • Limitations include:
    • Potentially limited generalizability
      • A greater proportion of individuals reported engaging in vigorous exercise than in previous surveys in patients with HCM.
      • Most individuals received care at high-volume care centers with expertise in HCM management.
  • Study funding: National Heart, Lung, and Blood Institute
  • Original study: Vigorous exercise in patients with hypertrophic cardiomyopathy [36]
  • Related AMBOSS article: Hypertrophe Kardiomyopathie

Stalled progress on reducing excess mortality in the Black population

One-Minute Telegram 76-2023-3/3

10-second takeaway

In the United States, the mortality rate in the Black population has exceeded that in the White population for over a hundred years. In this study, it was found that the excess mortality rate in Black individuals declined after 1999, but the rate plateaued in Black men in 2011 and in Black women in 2016 before sharply increasing in 2020, coinciding with the beginning of the COVID-19 pandemic. Evidence of ongoing racial disparity in mortality rates should prompt health care providers and policymakers to implement changes to reduce the millions of excess years of life lost in the Black population in the United States.

Study breakdown

  • Study population: non-Hispanic Black (denoted as Black) individuals and non-Hispanic White (denoted as White) individuals in the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiological Research (CDC WONDER) database
  • Methods: serial cross-sectional study
    • Study period: 1999–2020
    • Annual number of deaths, population size, and age-adjusted mortality rate per 100,000 individuals by race, age, and sex were obtained from CDC WONDER death certificate data.
    • Annual life expectancy in 5-year age groups was obtained from the National Center for Health Statistics life tables.
    • Yearly all-cause excess age-adjusted mortality rate in the Black population was calculated by subtracting each year’s age-adjusted mortality rate for White individuals from that for Black individuals.
    • Excess deaths in the Black population was estimated by comparing the number of deaths in the Black population to that in the White population, adjusting for differences in population size.
    • Annual years of potential life lost in the Black population was estimated by using life expectancy data for the White population as the reference for each 5-year age group.
  • Main results
    • Excess mortality rate per 100,000 individuals in the Black male population compared to the White male population
      • 1999–2011: decreased from 404 to 211 (P < 0.001)
      • 2012–2019: plateaued
      • 2020: increased to 395
    • Excess mortality rate per 100,000 individuals in the Black female population compared to the White female population
      • 1999–2015: decreased from 224 to 87 (P < 0.001)
      • 2016–2019: plateaued
      • 2020: increased to 192
    • Over the 22-year study period:
      • There were > 1.63 million excess deaths, representing > 80 million excess years of life lost in the Black population compared to the White population.
      • Highest excess mortality rate was due to heart disease
  • Limitations include:
    • The study was based on death certificate data, which is known to contain inaccuracies in reporting of ethnicity, race, and cause of death.
    • Disparities among individuals ≥ 85 years of age were not calculated because neither mortality rates nor population estimates for this subgroup are included in the CDC WONDER database.
  • Study funding: None
  • Original study: Excess mortality and years of potential life lost among the Black population in the US, 1999–2020 [37]
  • Related AMBOSS article: Bias, Stereotype und Diskriminierung in der Medizin - Ethnische Herkunft

Edition 75 - May 20, 2023toggle arrow icon

Contrast-enhanced CT to evaluate abdominal pain

One-Minute Telegram 75-2023-1/3

10-second takeaway

Contrast-enhanced CT (CECT) is the preferred modality for evaluation of acute abdominal pain in the emergency department (ED). However, unenhanced CT is used in patients with contraindications to contrast (e.g., renal impairment, hypersensitivity). This study found unenhanced CT to be significantly inferior to CECT in ED diagnosis of patients with acute abdominal pain. Contraindications to contrast should be weighed carefully against the diagnostic benefits of CT with contrast.

Study breakdown

  • Study population: 201 consecutive patients ≥ 18 years of age (mean age 50 years; 54% female; mean BMI 25.5) who had undergone dual-energy CECT (with oral and IV contrast) of the abdomen and pelvis in a single ED for the evaluation of acute abdominal pain
  • Methods: multicenter, retrospective diagnostic accuracy study
    • CECT reference interpretation was established by 3 radiologists.
    • Contrast was digitally subtracted to produce unenhanced CT images.
    • Unenhanced CT images were interpreted by 6 radiologists (1 faculty and 1 resident from 3 institutions) who were blinded to the reference CECT.
    • Primary outcome: diagnostic accuracy of unenhanced CT for the primary cause of abdominal pain
    • Secondary outcome: diagnostic accuracy of unenhanced CT for clinically significant incidental findings
  • Main results
    • Unenhanced CT was approximately 30% less accurate in identifying both the primary cause of abdominal pain and clinically significant incidental findings.
    • Overall diagnostic accuracy of faculty and residents was similar.
    • Overall diagnostic accuracy was slightly lower in older patients but was not affected by gender or BMI.
  • Limitations include:
    • Retrospective design evaluating imaging with contrast digitally subtracted rather than actual non-contrast-enhanced imaging.
    • The study did not evaluate the diagnostic accuracy of oral contrast-enhanced studies, which are less commonly avoided than IV contrast-enhanced studies.
  • Study funding: Michigan Institute for Clinical and Health Research
  • Original study: Diagnostic accuracy of unenhanced computed tomography for evaluation of acute abdominal pain in the emergency department [38]
  • Related AMBOSS article: Akutes Abdomen

Continue screening at-risk individuals for LTBI

One-Minute Telegram 75-2023-2/3

10-second takeaway

Up to 13 million individuals living in the US have latent tuberculosis infection (LTBI). Identification and treatment of LTBI are crucial in preventing the development of active TB and consequent transmissibility, morbidity, and death. The United States Preventive Services Task Force (USPSTF) has reaffirmed its 2016 recommendation to screen for LTBI in adults at risk for infection. Medical providers should use clinical judgment to determine screening intervals.

Recommendation breakdown

  • Recommendation: The USPSTF concluded with moderate certainty that there is a benefit to screening for LTBI in adults at risk for infection.
  • Applicable population
    • Asymptomatic adults ≥ 18 years of age at increased risk for TB infection
    • Risk factors for infection include having lived in:
      • Countries with high TB prevalence
      • Crowded living spaces (e.g., homeless shelters, prisons)
  • Additional information
    • This recommendation does not apply to:
      • Children and adolescents
      • Symptomatic individuals
      • Individuals who receive screening as standard of care (i.e., those with a history of immunosuppression, those who work in high-risk environments)
      • Individuals exposed to a person with active TB
    • Screening is performed by either tuberculin skin test (TST) or interferon-gamma release assay (IGRA).
    • Both tests have moderate sensitivity and high specificity for LTBI.
  • Limitations include:
    • The USPSTF did not find sufficient evidence to provide recommendations on screening frequency.
    • Available data comparing the outcomes of screened vs. unscreened individuals is limited.
  • Study funding: Agency for Healthcare Research and Quality (AHRQ)
  • Original study: Screening for latent tuberculosis infection in adults: US Preventive Services Task Force recommendation statement [39]
  • Related AMBOSS article: Tuberkulose

Eat, sleep, console, repeat

One-Minute Telegram 75-2023-3/3

10-second takeaway

Standard management of neonatal abstinence syndrome may lead to unnecessary use of opioids and long hospital stays. In this trial, infants managed with a function-based assessment and prioritization of nonpharmacological interventions (the Eat, Sleep, Console approach) were less likely to receive opioids and were discharged from the hospital earlier than infants managed with standard care, while safety outcomes were similar. The Eat, Sleep, Console approach for neonatal opioid withdrawal syndrome shows promise, but further research on long-term outcomes is needed.

Study breakdown

  • Study population: 1305 infants with neonatal opioid withdrawal syndrome born at ≥ 36 weeks gestation
  • Methods: multicenter, cluster-randomized, controlled trial at 26 hospitals
    • Randomization of hospitals to 1 of 8 blocks that were each randomly assigned a 3-month time period to transition from usual care to console care
    • At each site, infants were enrolled before and after (but not during) the transitional period.
    • Primary outcome: time from birth to being medically ready for discharge
    • Secondary outcomes: use of pharmacological treatment, duration of hospitalization
    • Safety outcomes from discharge to 3 months of age: in-hospital safety, unscheduled health care visits, nonaccidental trauma, and death
  • Main results
    • 837 infants met readiness for discharge.
    • Compared to the usual-care time period, infants treated during the console-care time period were:
    • Medically ready for discharge earlier (8.2 days vs. 14.9 days; 95% CI, 4.7–8.8)
    • Less likely to receive opioids (19.5% vs. 52%; relative risk, 0.38; 95% CI, 0.30–0.47)
    • Safety outcomes for infants managed before, during, and after the transitional period were similar.
  • Limitations include:
    • Long-term follow-up data is not available (to date).
    • Confounding temporal trends (e.g., earlier newborn discharge during the COVID-19 pandemic)
  • Study funding: National Institutes of Health
  • Original study: Eat, Sleep, Console approach or usual care for neonatal opioid withdrawal [40]
  • Related AMBOSS article: Opioidentzugsbehandlung

Edition 74 - May 6, 2023toggle arrow icon

Unclear benefit of skin cancer screening

One-Minute Telegram 74-2023-1/3

10-second takeaway

Skin cancer is the most common type of cancer in the US, but it seldom causes serious health problems or death. Melanoma, which has the highest skin cancer mortality rate, constitutes only 1% of skin cancers. The United States Preventive Services Task Force (USPSTF) has reaffirmed its 2016 statement that there is insufficient evidence to determine the balance of benefits and harms with regard to skin cancer screening in asymptomatic adolescents and adults. Medical providers should use their clinical judgment to determine if and when to screen asymptomatic individuals for skin cancer.

Recommendation breakdown

  • Recommendation: The USPSTF concluded that the current evidence is insufficient to determine the balance of benefits and harms of visual skin examination to screen for skin cancer in adolescents and adults.
  • Applicable population: adolescents and adults with no history of malignant or premalignant skin lesions, no current suspicious lesions, and no increased risk for skin cancer
  • Additional information
    • Visual skin examination is performed by the naked eye or with a dermatoscope.
      • Sensitivity for detecting melanoma is 40–70% and specificity is 86–98%.
      • Accuracy in detecting keratinocyte carcinoma (i.e., basal or squamous cell carcinoma) is unknown.
    • Available data on the effect of skin cancer screening on early cancer detection and/or mortality is limited and inconsistent.
    • Potential harms of skin cancer screening include adverse psychological effects (e.g., anxiety) and poor cosmetic outcomes following biopsy.
    • This recommendation does not apply to:
      • Individuals with a history of premalignant or malignant skin lesions or those presenting with a lesion suspicious for skin cancer
      • Individuals with a high risk of skin cancer, e.g., those with familial atypical multiple mole and melanoma (FAMMM) syndrome
  • Limitations include:
    • The USPSTF recommendation does not address skin self-exams and self-referral to dermatology, practices which are encouraged by the American Academy of Dermatology.
  • Study funding: Agency for Healthcare Research and Quality (AHRQ)
  • Original study: Screening for skin cancer: US Preventive Services Task Force recommendation statement [41]
  • Related AMBOSS articles: Melanom | Plattenepithelkarzinom der Haut | Basalzellkarzinom

Respect the decision to resect

One-Minute Telegram 74-2023-2/3

10-second takeaway

Guidelines used to inform decision-making on conservative versus surgical management of diverticulitis have relied heavily on retrospective and nonrandomized studies. In this prespecified 2-year follow-up of a randomized clinical trial, elective sigmoid resection was associated with fewer recurrences of diverticulitis and improved quality of life compared to conservative management in patients with complicated, recurrent, or persistent painful diverticulitis. Early elective sigmoid resection may be a good option for patients with diverticulitis, especially when conservative management does not adequately control symptoms.

Study breakdown

  • Study population: 90 adults in Finland with recurrent, complicated, or persistent painful diverticulitis (mean age 54 years, 69% women)
  • Methods: multicenter, parallel-group, open-label, individually randomized clinical trial
    • 1:1 randomization to elective laparoscopic sigmoid resection vs. conservative treatment
    • Surgical group had surgery scheduled within 3 months, followed by dietary counseling.
    • Conservative treatment group received dietary counseling and fiber supplementation for at least 6 months and could receive elective surgery from 6 months after randomization.
    • Outcomes: gastrointestinal quality of life index (GIQLI) scores at 12 and 24 months, recurrence and severity of diverticulitis, complications
  • Main results
    • Compared to the conservative treatment group, the surgery group had:
      • Modestly higher GIQLI scores at 12 months but not at 24 months (intention-to-treat analysis)
      • Significantly lower rates of recurrent diverticulitis at 24 months (11% vs. 61%)
      • Higher rates of postoperative complications at 24 months (10% vs. 5%)
    • 18% of patients in the conservative treatment group had surgery within 24 months.
  • Limitations include:
    • Small sample size due to early termination for benefit based on prespecified criteria
    • Significant crossover between the groups may have influenced the intention-to-treat results.
    • Analysis was based on a 2-year follow-up date. Longer-term follow-up results are not yet available.
  • Study funding: Vatsatautien Tutkimussäätiö Foundation, Mary and Georg Ehrnrooth’s Foundation, Martti I. Turunen Foundation, the Finnish Medical Foundation, and Helsinki University Hospital research funds
  • Original study: Quality-of-life and recurrence outcomes following laparoscopic elective sigmoid resection vs conservative treatment following diverticulitis: prespecified 2-year analysis of the LASER randomized clinical trial [42]
  • Related AMBOSS articles: Divertikulitis

A guide for heart failure guidelines

One-Minute Telegram 74-2023-3/3

10-second takeaway

Guideline-directed medical therapy (GDMT) has been shown to reduce the risk of death in patients with heart failure with reduced ejection fraction (HFrEF), but its implementation in clinical practice has been slow. In this retrospective validation study, a computable medication optimization algorithm (CMOA) accurately identified patients with HFrEF eligible for GDMT initiation or uptitration. Inclusion of computable algorithms into clinical decision support systems can alert clinicians to opportunities for medication optimization and may lead to improved outcomes in patients with HFrEF.

Study breakdown

  • Study population: patients participating in 2 clinical trials for the treatment of HFrEF
    • Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) trial: 841 adults (mean age 61 years, 31% women, 56% White)
    • Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION): 2130 adults (mean age 58 years, 28% women, 62% White)
  • Methods: retrospective validation of a CMOA using clinical data from prior studies
    • A CMOA was created using existing guideline recommendations and then coded into a computerized format.
    • The CMOA was applied retrospectively to individual participants in the previously published GUIDE-IT and HF-ACTION studies.
    • Each drug class used in GDMT of HFrEF was evaluated for initiation or dosage modification by the CMOA.
    • Recommendations generated by the CMOA were compared to actual medication regimen changes documented during study visits.
    • A CMOA-generated medication optimization score (MOS) at each visit was used to quantify GDMT optimization by study clinicians.
  • Main results
    • Overall, the CMOA identified the need for GDMT optimization in 73% of patients.
    • CMOA identified multiple missed opportunities for GDMT optimization during GUIDE-IT visits.
      • An opportunity to initiate an ACEI/ARB, BB, or MRA had been missed in 79%, 43%, and 84% of visits, respectively.
      • An opportunity to titrate an ACEI/ARB or BB had been missed in 76% and 63% of visits, respectively.
    • Higher baseline MOS was associated with lower risk of death or hospitalization.
      • GUIDE-IT: lower risk of cardiovascular death and hospitalization for heart failure (HR, 0.41; 95% CI, 0.21–0.80)
      • HF-ACTION: lower all-cause death and hospitalization (0.61; 0.44–0.84)
  • Limitations include:
    • Results based on clinical trial data may not be generalizable to data collected with typical electronic medical record systems.
    • Some patients were excluded from analysis because follow-up data was not available.
    • Recent guidelines that include newer agents for HFrEF were not incorporated into the algorithm.
  • Study funding: Agency for Health Research and Quality, National Institutes of Health, American Health Association Health IT Strategically Focused Research Network, Veterans Affairs
  • Original study: A computable algorithm for medication optimization in heart failure with reduced ejection fraction [43]
  • Related AMBOSS article: Herzinsuffizienz

Edition 73 - April 22, 2023toggle arrow icon

The high price of insulin costs

One-Minute Telegram 73-2023-1/3

10-second takeaway

Nonadherence to diabetes medications contributes to adverse outcomes, including inadequate glycemic control and diabetic ketoacidosis. While insulin costs for Medicare beneficiaries were capped by the 2022 Inflation Reduction Act, out-of-pocket expenses remained high for other patients who require insulin. In this study of the prevalence of cost-related insulin rationing, 1 in 5 adults under 65 years of age with diabetes reported rationing. Since the study was conducted, key insulin manufacturers have capped the out-of-pocket cost of insulin at $35 a month, which may improve affordability and reduce insulin rationing.

Study breakdown

  • Study population: 495 adults < 65 years of age (mean age 50.7 years) with insulin-treated diabetes
    • 51% women
    • 17% Hispanic, 20% Black, 56% non-Hispanic White
  • Methods: cross-sectional analysis of data from the 2021 National Health Interview Survey (NHIS)
    • Estimation of cost-related insulin rationing
    • Participants were asked if any of the following occurred in the past 12 months in order to save money:
  • Main results
    • Overall, 20.4% (95% CI, 16.2% to 25.3%) reported cost-related insulin rationing.
    • Rationing rates were highest among individuals who were:
      • Black: 26.7% (16% to 41.2%)
      • Middle-income: 30.2% (21.7% to 40.3%)
      • Underinsured or uninsured: 33.7% (25.2% to 43.5%)
  • Limitations include:
    • Use of self-reported data
    • Small sample size
    • Susceptibility to nonresponse bias, given the 51% NHIS response rate
  • Study funding: National Institutes of Health
  • Original study: Cost-related insulin rationing in US adults younger than 65 years with diabetes [44]
  • Related AMBOSS articles: Diabetes mellitus | Patientenversorgung und Gesundheitssystem

Providing a boost for treatment-resistant depression

One-Minute Telegram 73-2023-2/3

10-second takeaway

Depression among older adults is a major health concern with potentially severe consequences. In this trial comparing augmentation and switching regimens for older adults with treatment-resistant depression, augmentation with aripiprazole was the safest and most effective strategy, although overall remission rates were low. Augmenting rather than switching medications may be a promising strategy for treatment-resistant depression in this population.

Study breakdown

  • Study population: 742 adults ≥ 60 years of age (mean age ∼ 70 years; predominantly female and White) with treatment-resistant depression
  • Methods: two-step, open-label randomized trial
    • Step 1 (n = 619): randomized 1:1:1 to current antidepressant plus aripiprazole, current antidepressant plus bupropion, or switching current treatment to bupropion
    • Step 2 (individuals not in remission after or not eligible for step 1; n = 248): randomized 1:1 to augmentation with lithium or switch to nortriptyline
    • Primary outcome: change in psychological well-being score
    • Secondary outcome: remission of depression
    • Safety outcomes: falls and serious adverse events
    • Follow-up: week 10 after each step
  • Main results: Psychological well-being scores increased across all groups.
    • Step 1: The aripiprazole-augmentation group had the greatest improvement in well-being scores, highest incidence of depression remission (29%), and a low reported number of falls. Aripiprazole-augmentation was significantly superior to the switch-to-bupropion approach.
    • The bupropion-augmentation group had the highest rate of falls (0.55 per patient) and injurious falls (0.25 per patient).
    • Step 2: no significant difference between the groups
    • Serious adverse events were similar among all groups.
  • Limitations include:
    • Lack of participant blinding may have influenced the perceived benefit of receiving two drugs rather than one (performance bias).
    • Due to the lack of a control group, the superiority of the tested interventions over continuing the same treatment could not be established.
    • Given the low enrollment rates, the study may have been underpowered to detect differences in effectiveness and safety.
    • Treatment adherence was low, which may have led to an underestimation of treatment efficacy.
  • Study funding: Patient-Centered Outcomes Research Institute
  • Original study: Antidepressant augmentation versus switch in treatment-resistant geriatric depression [45]
  • Related AMBOSS article: Unipolare Depression

The financial penalty on being a female physician

One-Minute Telegram 73-2023-3/3

10-second takeaway

Female physicians in the US earn significantly less than their male counterparts. In this study of differences in earnings between male and female physicians, female physicians earned less than their male counterparts across all ages and family structures. Marriage with children was associated with the greatest loss of lifetime earnings, primarily because of fewer hours worked. Further work is needed by health leadership to address gender-based earnings disparities.

Study breakdown

  • Study population: 95,435 physicians 25–64 years of age (mean age 44 years) who responded to the American Community Survey between 2005 and 2019
    • 67.3% White, 19.8% Asian, 4.8% Black, 5.9% Hispanic, 2.2% other
    • 35.8% female
  • Methods: retrospective, cross-sectional study
    • Primary outcomes: annual earned income, hours worked per week, and earnings per hour
    • Differences were measured by:
      • Sex
      • Age
      • Family status: single (i.e., never married, widowed, divorced, or separated), married, and with or without children in the household
  • Main results
    • Compared to male physicians, female physicians:
      • Earned less regardless of age or family structure (average of $194,000 vs. $285,000 per year)
      • Earned 21.4% to 23.9% less per hour
    • No difference in hours worked per week between single female and male physicians
    • Married female physicians worked 7.0% fewer hours (95% CI, 5.6% to 8.4%) than married male physicians.
    • Female physicians with children worked 17.5% fewer hours (16.8% to 18.2%) than male physicians with children.
  • Limitations include:
    • The study did not adjust for physician specialty or practice setting.
    • The definition of marriage and whether respondents in other forms of unions were counted as married or single were not clear.
    • Self-reported hours are subject to recall bias.
  • Study funding: Gordon and Betty Moor Foundation
  • Original study: Marriage, children, and sex-based differences in physician hours and income [46]
  • Related AMBOSS article: Bias, Stereotype und Diskriminierung in der Medizin

Edition 72 - April 8, 2023toggle arrow icon

An infusion of hope for pneumonia survival

One-Minute Telegram 72-2023-1/3

10-second takeaway

In spite of advances in antibiotic therapy and supportive respiratory care, community-acquired pneumonia (CAP) remains the ninth leading cause of death in the US. In this randomized controlled trial, continuous IV hydrocortisone significantly lowered the risk of death in patients with severe CAP compared to placebo. The early addition of hydrocortisone to the treatment regimen of severe CAP may improve patient outcomes.

Study breakdown

  • Study population: 800 adults (≥ 18 years) admitted to ICUs in France with clinical and radiographic evidence of severe CAP
  • Methods: phase 3, multicenter, double-blind, randomized controlled trial
    • Randomized 1:1 to receive placebo or a continuous infusion of hydrocortisone 200 mg IV daily started within 24 hours of onset of severity criteria and continued for 4 days, followed by an 8–14 day taper regimen
    • All participants received antibiotics and standard supportive care.
    • Primary outcome: death by day 28
    • Secondary outcomes included:
      • Death from any cause within 90 days
      • New requirement for endotracheal intubation
      • New requirement for vasopressor therapy
    • Safety criteria included: secondary infection, gastrointestinal bleed, daily insulin administration by day 7
    • The trial was conducted prior to the COVID-19 pandemic
  • Main results
    • Primary and secondary outcomes: significantly better with hydrocortisone compared to placebo
      • Death by day 28: 6.2% vs. 11.9% (absolute difference -5.6%; 95% CI, -9.6 to -1.7)
      • Death by 90 days: 9.3% vs. 14.7% (absolute difference, -5.4%; 95% CI, -9.9 to -0.8)
      • New endotracheal intubation: 18.0% vs. 29.5% (HR, 0.59; 95% CI, 0.40 to 0.86)
      • Vasopressor administration: 15.3% vs. 25.0% (HR, 0.59; 95% CI, 0.43 to 0.82)
    • Safety outcomes
  • Limitations include
    • Exclusion of individuals with septic shock
    • Adverse neuromuscular and neuropsychiatric effects were not reported.
    • Bolus dosing of hydrocortisone was not tested.
    • A small number of immunocompromised participants limits generalizability to this population
  • Study funding: French Ministry of Health
  • Related AMBOSS article: Pneumonie
  • Original study: Hydrocortisone in severe community-acquired pneumonia [47]

Metformin may defend against osteoarthritis

One-Minute Telegram 72-2023-2/3

10-second takeaway

Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability in the US. Animal studies suggest metformin may have properties that prevent or modify the progression of OA. This retrospective cohort study found that the use of metformin for the treatment of diabetes was associated with a significant reduction in the risk of developing OA compared to the use of sulfonylurea. Metformin may be protective against osteoarthritis, but study limitations currently preclude clinical application.

Study breakdown

  • Study population: 41,874 adults aged ≥ 40 years (mean age 62 years) with newly diagnosed type 2 diabetes treated with metformin or sulfonylurea as monotherapy and no prior history of OA, inflammatory arthritis, or joint replacement
    • 41.8% female
    • 68% White, 13% Black, 13% Hispanic, 4% Asian
  • Methods: retrospective cohort study using data from a large deidentified database in the US.
    • Exposed group: individuals who received metformin for ≥ 90 days
    • Control group: individuals who received a sulfonylurea for ≥ 90 days
    • Primary endpoint: time to new diagnosis of OA ≥ 90 days after the first prescription fill date
    • Secondary endpoint: time to joint replacement ≥ 90 days after the first prescription fill date
    • Mean duration of treatment: 12 months
  • Main results
    • Compared to patients who received sulfonylurea, patients who received metformin were:
      • 24% less likely to develop OA (aHR, 0.76; 95% CI, 0.68–0.85)
      • Equally likely to undergo joint replacement (aHR, 0.80; 95% CI, 0.5–1.27)
  • Limitations include:
    • Results may have been influenced by unmeasured confounders given the retrospective study design.
    • Potential confounding factors associated with both metformin effect and the risk of developing OA (e.g., lower body mass index) were not included in the analysis.
    • Low numbers of patients using sulfonylureas necessitated using data from patients who had been switched from metformin to a sulfonylurea in both groups, which may have introduced bias.
    • Not generalizable to individuals without diabetes or with type 1 diabetes
  • Study funding: National Institutes of Health, Department of Veterans Affairs Merit Award, and Population Health Sciences Data Core
  • Related AMBOSS Article: Arthrose | Metformin
  • Original study: Development of osteoarthritis in adults with type 2 diabetes treated with metformin vs. a sulfonylurea [48]

Aggressive therapy may not be the key to survival for localized prostate cancer

One-Minute Telegram 72-2023-3/3

10-second takeaway

Aggressive therapy for prostate cancer (i.e., prostatectomy and/or radiotherapy) can reduce local disease progression and metastasis, but may lead to unnecessary procedures and serious side effects without improving long-term survival. In this long-term randomized clinical trial, fifteen-year mortality from prostate cancer was low and unaffected by the choice of initial treatment. Active monitoring may be an acceptable management option for patients with localized prostate cancer who wish to avoid the harms associated with aggressive therapy.

Study breakdown

  • Study population
    • 1,643 men (median age 62 years) with clinically localized prostate cancer detected by PSA testing and a life expectancy ≥ 10 years
    • More than one-third had intermediate or high-risk disease at the time of diagnosis.
  • Methods: long-term, randomized clinical trial
    • Randomization: 1:1:1 to standard treatment protocols for active monitoring, prostatectomy, or radiotherapy
    • Monitoring: scheduled monitoring of PSA + management review and intervention triggered by increase in PSA ≥ 2 ng/dL or clinical concern
    • Primary outcome: death from prostate cancer
    • Secondary outcomes: all-cause mortality, metastases, clinical progression, and initiation of long-term androgen-deprivation therapy
    • Median follow-up: 15 years
  • Main results
    • No significant difference in prostate cancer mortality (prostate cancer specific survival was approximately 97% in all groups; P = 0.53)
    • No significant difference in all-cause mortality among trial groups
    • Metastasis was more common with active monitoring (9.4%) than prostatectomy (4.7%) or radiotherapy (5.0%).
    • Local disease progression was more common with active monitoring (25.9%) than prostatectomy (10.5%) or radiotherapy (11%).
    • Androgen deprivation therapy was more common with active monitoring (12.7%) than prostatectomy (7.2%) or radiotherapy (7.7%).
    • Proportion of patients who had received aggressive therapy by the end of 15 years of follow-up:
      • 61.1% in the active monitoring group
      • 90.4% in the prostatectomy group
      • 92.5% in the radiotherapy group
  • Limitations include: Diagnostic and treatment options have evolved since initiation of the trial.
  • Study funding: National Institute for Health and Care Research in the United Kingdom
  • Related AMBOSS article: Prostatakarzinom
  • Original study: Fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer. [49]

Q1 2023toggle arrow icon

Edition 71 - March 25, 2023toggle arrow icon

TRUNCATE-TB: Sometimes less isn’t less

One-Minute Telegram 71-2023-1/3

10-second takeaway

The currently recommended treatment regimen for drug-susceptible pulmonary tuberculosis (TB) may lead to overtreatment, nonadherance, and increased drug resistance. In this open-label trial with HIV-negative patients, a two-month bedaquiline-linezolid treatment regimen followed by extended treatment only for persistent or relapsing TB was noninferior to a standard six-month regimen with respect to death, persistent disease, and prolonged treatment. Shorter treatment regimens combined with extended monitoring may prevent overtreatment and reduce the cost of care.

Study breakdown

  • Study population: 674 HIV-negative adults aged 18–65 years with symptoms or radiographic evidence of TB and a positive nucleic acid test for TB without rifampin resistance
  • Methods
    • International, randomized, phase 2–3 prospective, open-label noninferiority trial
    • Randomization to either of the following:
      • Standard therapy: 8 weeks of isoniazid (H) + rifampin (R) + pyrazinamide (Z) + ethambutol (E) followed by 16 weeks of H + R
      • Shortened therapy: 8-week treatment with one of four different drug combinations followed by monitoring, extended treatment for persistent disease, and/or treatment for relapse
    • Regular monitoring with symptom assessment and sputum smears
    • Primary outcomes: composite of death, ongoing treatment, or active tuberculosis
    • Follow-up: at 96 weeks
  • Main results
    • Initial treatment with 8 weeks of H + Z + E + bedaquiline-linezolid was noninferior to standard therapy (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1).
    • Initial treatment with 8 weeks of H + Z + E + linezolid + high-dose R did not meet noninferiority criteria.
    • Recruitment to the remaining two therapy groups was discontinued due to sample size considerations.
    • No difference in adverse events, death, or acquired drug resistance between groups
  • Limitations include:
    • Open-label design
    • Exclusion of HIV-positive participants
  • Study funding: Singapore National Medical Research Council and others
  • Original study: Treatment strategy for rifampin-susceptible tuberculosis [50]
  • AMBOSS links: Tuberkulose

Statin your case: high-intensity therapy vs. treat-to-target for elevated LDL-C

One-Minute Telegram 71-2023-2/3

10-second takeaway

Statins reduce the risk of major cardiovascular events in patients with coronary artery disease (CAD), but the best strategy for initiating statin therapy remains unclear. In this trial, moderate-intensity statin therapy followed by titration to a targeted LDL-C level was noninferior to high-intensity statin therapy without a targeted LDL-C in reducing the risk for a composite of major cardiovascular events. In patients with CAD, titration of moderate-intensity statin therapy to a target LDL-C goal may be as effective and safe as initiation of treatment with a high-intensity statin.

Study breakdown

  • Study population: 4400 adults with clinically diagnosed CAD (mean age 65 years; 72% male)
  • Methods
    • Multicenter, open-label, randomized, noninferiority trial
    • Randomization of statin therapy 1:1 to:
    • Primary endpoint: composite of all-cause death, myocardial infarction, stroke, or coronary revascularization
    • Follow-up: 3 years
  • Main results
    • Titrated-intensity statin therapy was noninferior to high-intensity statin therapy.
      • Primary endpoint: titrated-intensity group 8.1% vs. high-intensity group 8.7% (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points])
      • All-cause death (absolute difference, < 0.1% [95% CI, -0.9% to 0.9%])
      • Myocardial infarction (absolute difference, -0.5% [95% CI, -1.1% to 0.1%])
      • Stroke (absolute difference, -0.5% [95% CI, -1.1% to 0.1%])
  • Limitations include:
    • Open-label design
    • Study may have been underpowered, given lower-than-anticipated event rates.
    • The study did not consider the use of statins for primary prevention.
    • The study does not provide evidence on whether treatment-to-target results in improved outcomes, reduced adverse effects, and/or a better cost-benefit ratio compared with high-dose statin therapy.
  • Study funding: Samjin Pharmaceutical and Chong Kun Dang Pharmaceutical
  • Original study: Treat-to-target or high-intensity statin in patients with coronary artery disease: a randomized clinical trial [51]
  • AMBOSS links: Atherosklerose | Koronare Herzkrankheit | Dyslipidämien

NOSTONE left unturned

One-Minute Telegram 71-2023-3/3

10-second takeaway

Thiazide diuretics are commonly used to prevent the recurrence of nephrolithiasis, but studies supporting this practice are limited. In this trial with patients in Switzerland with a history of recurrent nephrolithiasis, daily hydrochlorothiazide (HCTZ) did not reduce the incidence of nephrolithiasis recurrence compared to placebo but did cause more hypokalemia, gout, and plasma creatinine elevation. The risks of daily thiazide diuretic use should be weighed against the potential lack of benefit for prevention of recurrent nephrolithiasis.

Study breakdown

  • Study population: 416 adults with a history of recurrent calcium-containing kidney stones within 10 years (median age 49 years; 20% female; 99% White)
  • Methods
    • Double-blind multicenter randomized clinical trial
    • Randomized 1:1:1:1 to HCTZ 12.5 mg, 25 mg, or 50 mg, or a placebo once daily
    • Primary outcome: a composite of symptomatic or radiologic recurrence of kidney stones
    • Median follow-up: 2.9 years
  • Main results
    • Stone recurrence was 59% in the placebo group and did not differ significantly compared to placebo in the HCTZ treatment groups:
      • 12.5 mg HCTZ group: 59% (rate ratio 1.33; 95% CI, 0.92–1.93)
      • 25 mg HCTZ group: 56% (rate ratio, 1.24; 95% CI, 0.86–1.79)
      • 50 mg HCTZ group: 49% (rate ratio, 0.92; 95% CI, 0.63–1.36)
    • Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and plasma creatinine elevation > 150% baseline were more common in participants taking HCTZ than those taking placebo.
    • Nonadherance rate was 26%.
  • Limitations include:
    • Underrepresentation of women and people of color
    • Results are not generalizable to the prevention of recurrence after a first episode of nephrolithiasis.
    • Study duration of 3 years limits generalizability to longer treatment periods.
    • High incidence of nonadherance may have introduced bias toward the null hypothesis.
  • Study funding: Swiss National Science Foundation; Inselspital, Bern University Hospital
  • Original study: Hydrochlorothiazide and prevention of kidney stone recurrence [52]
  • AMBOSS links: Nephrolithiasis

Edition 70 - March 11, 2023toggle arrow icon

The efficacy of the RSV vaccine is nothing to sneeze at

One-Minute Telegram 70-2023-1/3

10-second takeaway

Respiratory syncytial virus (RSV) is an important cause of death and disease in older adults, accounting for over 12,000 deaths per year among this population in the US alone. In this large-scale, placebo-controlled phase 3 trial, a single dose of RSV vaccine had an acceptable safety profile and significantly reduced the incidence of RSV infection and RSV-related lower respiratory tract disease in older adults. This RSV vaccine may be a safe and effective method for protecting this population from both mild and severe manifestations of RSV infection.

Study breakdown

  • Study population: 24,966 adults, ≥ 60 years of age (mean age 69.5 years; 52% female; 39% with comorbidities)
  • Methods
    • Ongoing international, randomized, phase 3 trial
    • Randomized 1:1 to receive a single dose of the RSVPreF3 OA vaccine vs. placebo for one RSV season
    • Primary outcome: vaccine efficacy against RSV-related lower respiratory tract disease
    • Subgroup safety assessment, utilizing solicited and unsolicited reporting of injection site and systemic reactions
    • Median follow-up: 6.7 months
  • Main results
    • Vaccine efficacy compared with placebo
      • 82.6% (96.95% CI, 57.9–94.1) for prevention of RT-PCR-confirmed RSV-related lower respiratory tract disease (primary outcome)
      • 94.1% (95% CI, 62.4–99.9) for prevention of severe RSV-related lower respiratory tract disease
      • 71.7% (95% CI, 56.2–82.3) for prevention of RSV-related acute respiratory infection
      • Similar efficacy for RSV A and B subtypes
    • Adverse events associated with the vaccine were transient and of mild to moderate severity.
  • Limitations include: small number of participants > 80 years of age
  • Study funding: GlaxoSmithKline Biologicals
  • Original study: Respiratory syncytial virus prefusion F protein vaccine in older adults [53]
  • AMBOSS links: Geriatrie | Akute Bronchitis

USPSTF reaffirms: Do not screen asymptomatic patients for HSV!

One-Minute Telegram 70-2023-2/3

10-second takeaway

Serologic testing for herpes simplex virus (HSV) in patients without symptoms of genital herpes has a high false-positive rate, and whether treatment for asymptomatic HSV is warranted is controversial. The United States Preventive Services Task Force (USPSTF) has reaffirmed its recommendation against routine serologic screening for genital HSV in immunocompetent, HIV-negative, asymptomatic adolescents and adults, including pregnant individuals. Medical providers should avoid routine serologic screening for HSV in this population.

Recommendation breakdown

  • Recommendation: The USPSTF recommends against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including pregnant individuals.
  • Applicable population: adolescents and adults, including pregnant individuals, without a known medical history, signs, and/or symptoms of genital herpes
  • Additional information
    • Routine serologic screening for HSV has a low predictive value and a high rate of false positives in asymptomatic patients.
    • The benefit of antiviral medications in asymptomatic patients with serologic evidence of HSV infection is unclear.
    • This recommendation does not apply to:
      • Individuals with HIV or other immunosuppressive disorders
      • Individuals requesting testing who have signs, symptoms, or a history of genital herpes
  • Limitations include:
    • Need for more studies to assess the benefits and risks of screening for and management of genital herpes in asymptomatic individuals
    • Need for more studies to evaluate the potential benefits and risks of HSV screening in populations disproportionately affected by HSV
  • Study funding: Agency for Healthcare Research and Quality (AHRQ)
  • Original study: Serologic screening for genital herpes infection: US Preventive Services Task Force reaffirmation recommendation statement [54]
  • AMBOSS links: Herpesvirus-Infektionen | Sexuell übertragbare Infektionen

Sleep tight and keep your heart right

One-Minute Telegram 70-2023-3/3

10-second takeaway

There is a clear correlation between disordered sleep and the development of cardiovascular disease (CVD). In this cross-sectional, community-based evaluation, irregularities in sleep duration and sleep onset timing were associated with subclinical atherosclerosis. Maintaining a regular sleep schedule with consistent sleep duration may be an important lifestyle recommendation for the prevention of CVD.

Study breakdown

  • Study population: 2032 US adults between 45 and 84 years of age (mean age 68 years; 53% female; 38% White; 28% Black; 23% Hispanic; 11% Chinese American)
  • Methods
    • Cross-sectional evaluation of participants in a longitudinal cohort study of atherosclerosis across six US communities
    • Sleep regularity was assessed with wrist-worn actigraphs and sleep diaries.
    • Standard deviations (SD) of sleep duration and sleep onset timing were determined for each participant.
    • The presence of subclinical CVD was determined using standard testing for:
      • Coronary artery calcium (CAC)
      • Carotid intima-media thickness (cIMT)
      • Carotid plaque
      • Ankle-brachial index (ABI)
  • Main results
    • Participants with irregular sleep duration (SD > 120 minutes) had a significantly higher likelihood of elevated CAC (prevalence ratio, 1.33; 95% CI, 1.03–1.71) and abnormal ABI (1.75; 1.03–2.95) than those with regular sleep duration (SD ≤ 60 minutes).
    • Participants with irregular sleep onset timing (SD > 90 minutes) had higher CAC levels (1.39; 1.07–1.82) than those with regular sleep timing (SD ≤ 30 minutes).
  • Limitations include: Causality cannot be inferred given the cross-sectional study design.
  • Study funding
    • National Heart, Lung, and Blood Institute
    • National Center for Advancing Translational Sciences
  • Original study: Sleep irregularity and subclinical markers of cardiovascular disease: the multi-ethnic study of atherosclerosis [55]
  • AMBOSS links: Atherosklerose und kardiovaskuläre Prävention | Insomnie

Edition 69 - February 25, 2023toggle arrow icon

The jury is still out on the best treatment approach to early sepsis

One-Minute Telegram 69-2023-1/3

10-second takeaway

The best approach to sepsis management is an area of active inquiry. This randomized trial of a restrictive vs. liberal fluid strategy for early management of sepsis-induced hypotension showed no difference in in-hospital mortality between the two groups. Whether these findings will affect current sepsis management guidelines remains to be seen.

Study breakdown

  • Study population: 1563 adults < 4 hours after initial diagnosis of sepsis-induced hypotension refractory to initial resuscitation (1000–3000 mL of IV crystalloid fluid)
  • Methods: multicenter, randomized, nonblinded superiority trial
    • Randomized 1:1 to restrictive fluid strategy (prioritizing early vasopressor use with rescue fluids permitted) vs. liberal fluid strategy (prioritizing early fluid boluses with rescue vasopressors permitted) for 24 hours
    • Primary outcome: all-cause mortality prior to discharge by day 90
  • Main results
    • Patients in the restrictive fluid strategy group received an average of 2100 mL less IV fluid (3300 mL vs. 5400 mL) and were significantly more likely to receive vasopressors than the liberal fluid strategy group (59% vs. 37%).
    • No significant difference in mortality before discharge by day 90: 14.0% in the restrictive fluid strategy group; 14.9% in the liberal fluid strategy group (est. mean difference, -0.9%; 95% CI, -4.4 to 2.6)
    • No significant differences in invasive mechanical ventilation, onset of ARDS within the first week of treatment, initiation of renal replacement therapy, or severe adverse events
  • Limitations include:
    • Results may not be generalizable to patients with volume overload or volume depletion on presentation, who were excluded from the study population, or to patients who develop sepsis in the hospital, since most participants were enrolled in the emergency department.
    • Trial may not have been powered to detect differences in outcomes among patient subgroups (e.g., patients with CHF and/or kidney disease)
  • AMBOSS links: Sepsis | Flüssigkeits- und Volumentherapie
  • Original study: Early restrictive or liberal fluid management for sepsis-induced hypotension [56]
  • Authors: The National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network
  • Journal: N Engl J Med
  • Study funding: NHLBI of the National Institutes of Health

Shed those meds: decreasing polypharmacy by actively deprescribing

One-Minute Telegram 69-2023-2/3

10-second takeaway

Polypharmacy, with its associated costs and adverse effects, is a growing concern among older adults that is often exacerbated by additional prescriptions upon hospital discharge. In this randomized clinical trial, hospitalized patients assigned to a deprescription intervention upon discharge to a post acute care (PAC) facility were prescribed significantly fewer medications at PAC facility discharge and at 90-day follow-up than patients receiving usual care. To reduce polypharmacy in older adults, hospital providers should consider introducing deprescription interventions before discharge.

Study breakdown

  • Study population: 372 adults over 50 years of age (mean age 76 years, 62% women) taking at least five prehospital medications (median number 16) and being discharged from the hospital to a PAC facility
  • Methods: randomized clinical trial
    • Randomized 1:1 to receive the “Shed-MEDS intervention” (comprehensive medication review prompting deprescribing recommendations implemented with patient approval and continued throughout PAC facility stay) vs. usual care
    • Follow-up at PAC facility discharge and 90 days post-PAC discharge
  • Main results: Compared to usual care the intervention group had
    • 14% fewer medications at PAC facility discharge (mean ratio, 0.86; 95% CI, 0.80–0.93) and 15% fewer medications 90 days post-PAC discharge (0.85; 0.78–0.92)
    • Significantly lower medication dosages as measured by the Drug Burden Index
    • Reduced exposure to potentially inappropriate medications
    • Similar rates of adverse drug events
  • Limitations include:
    • Potentially limited generalizability, as patients were enrolled at a single academic medical center
    • By increasing awareness of polypharmacy, the study may have also led to avoidance of overprescribing for the nonintervention group, thus limiting the observed intervention effect.
  • AMBOSS link: Geriatrie
  • Original study: Deprescribing medications among older adults from end of hospitalization through postacute care: a Shed-MEDS randomized clinical trial [57]
  • Authors: Vasilevskis EE, Shah AS, Hollingsworth EK, et al.
  • Journal: JAMA Intern Med
  • Study funding: National Institute on Aging of the National Institutes of Health

Does vitamin D prevent diabetes in people with prediabetes?

One-Minute Telegram 69-2023-3/3

10-second takeaway

Factors associated with the prevention of type 2 diabetes in individuals at risk are an area of active research. In this systematic review and metaanalysis of three randomized trials, patients with prediabetes who received oral vitamin D therapy had a moderately reduced risk of developing diabetes compared to those who received placebo. Oral vitamin D therapy may be a safe and effective adjunct to other measures for the prevention of diabetes in patients with prediabetes.

Study breakdown

  • Study population: 4190 adults (mean age 61 years, 44% women, 51% White, 33% Asian, 15% Black) with prediabetes
  • Methods: systematic review and individual participant data metaanalysis from three randomized clinical trials
  • Main results: Compared to patients receiving placebo, patients in the vitamin D group had
    • Lower rates of developing diabetes (22.7% vs. 25%; adjusted HR, 0.85; 95% CI, 0.75–0.96)
    • Higher rates of normalization of glucose regulation (14.4% vs. 11.1%; rate ratio, 1.30; 1.16–1.46)
    • Similar rates of adverse events (kidney stones, hypercalcemia, hypercalciuria) and death
  • Limitations include:
    • Results are not generalizable to populations without prediabetes or other dosages of vitamin D replacement.
  • AMBOSS links: Diabetes mellitus
  • Original study: Vitamin D and risk for type 2 diabetes in people with prediabetes [58]
  • Authors: Pittas AG, Kawahara T, Jorde R, et al.
  • Journal: Ann Intern Med
  • Study funding: None

Edition 68 - February 11, 2023toggle arrow icon

After orthopedic trauma, two aspirin a day keep fatal blood clots away

One-Minute Telegram 68-2023-1/3

  • Background: Low molecular weight heparin (LMWH) is recommended for thromboprophylaxis in patients with fractures. This trial set out to determine if aspirin is noninferior to LMWH as thromboprophylaxis after a fracture.
  • Study population: 12,211 adults (median age 44 years, 62% male) with any pelvic, acetabular, and/or surgically repaired extremity fracture
  • Methods
    • Pragmatic, multicenter, randomized noninferiority trial
    • Randomized 1:1 to aspirin 81 mg twice daily or LMWH 30 mg twice daily
    • Duration of therapy followed local protocol.
  • Main results
    • Mortality was similar between aspirin (0.78%) and LMWH (0.73%) groups (96.2% CI, -0.27 to 0.38).
    • Incidence of pulmonary embolism was the same in both groups (1.49%).
    • Deep vein thrombosis occurred more frequently in the aspirin group than in the LMWH group (2.51% vs. 1.71%; 95% CI, 0.28–1.31).
    • Safety outcomes: Incidence of bleeding complications and other serious adverse events was similar between groups.
  • Limitations include:
    • Open-label design may have introduced surveillance bias.
    • Variations in the duration of thromboprophylaxis may have influenced outcomes.
    • Generalizability to other patient groups is limited.

The take-home message?

In this large, open-label trial, aspirin was noninferior to LMWH as thromboprophylaxis after a fracture. Aspirin may be a well-tolerated, effective, inexpensive, and convenient alternative to LMWH following orthopedic trauma.

  • AMBOSS links: Tiefe Beinvenenthrombose | Lungenarterienembolie
  • Original study: Aspirin or low-molecular-weight heparin for thromboprophylaxis after a fracture [59]
  • Authors: Major Extremity Trauma Research Consortium
  • Journal: N Engl J Med
  • Study funding: Patient-Centered Outcomes Research Institute

Loop me in: torsemide or furosemide for heart failure?

One-Minute Telegram 68-2023-2/3

  • Background: Loop diuretics are a cornerstone in the management of heart failure, and torsemide may be more effective than other diuretics because of its high bioavailability and long half-life. This study set out to determine if torsemide is more effective than furosemide for reducing mortality in patients hospitalized for acute heart failure.
  • Study population: 2859 patients (median age 65 years, 36.9% female) hospitalized for de novo heart failure or worsened chronic heart failure
  • Methods
    • Open-label, pragmatic, randomized comparative-effectiveness study
    • Randomized 1:1 to torsemide or furosemide on discharge
    • Dosage was clinician-determined (recommended drug equivalency was 1 mg torsemide to 2–4 mg furosemide).
    • Recruitment ended upon reaching a predetermined number of all-cause deaths (median follow-up was 17.4 months).
  • Main results
    • No difference in all-cause mortality: 26.1% in the torsemide group, 26.2% in the furosemide group (HR, 1.02; 95% CI, 0.89–1.18)
    • No difference in total hospitalizations: 940 in the torsemide group, 987 in the furosemide group (RR, 0.94; 0.84–1.07)
    • Mean furosemide equivalent diuretic doses were similar at discharge in both groups: 79.1 mg in the furosemide group, 79.5 mg in the torsemide group
    • Crossover occurred in 5.4%; nonadherence at 6 months was 9.5%.
  • Limitations include:
    • Early attainment of the predetermined study endpoint resulted in a smaller-than-anticipated sample size, which limited subgroup analyses and assessments of subtle benefits and harms.
    • All-cause mortality may have been too broad an outcome to detect subtle differences between drugs.
    • High crossover and nonadherence rates may have introduced bias toward neutral results.

The take-home message?

In this large open-label randomized clinical trial, the use of torsemide vs. furosemide following hospitalization for heart failure did not result in a significant difference in all-cause mortality at 12 months. These results suggest that the pharmacokinetic advantages of torsemide may not be clinically significant, but study limitations necessitate cautious interpretation.

  • AMBOSS links: Dekompensierte Herzinsuffizienz
  • Original study: Effect of torsemide vs furosemide after discharge on all-cause mortality in patients hospitalized with heart failure: the TRANSFORM-HF randomized clinical trial [60]
  • Authors: Mentz RJ, Anstrom KJ, Eisenstein EL et al.
  • Journal: JAMA
  • Study funding: National Institutes of Health

They tested their poo, but didn’t follow through

One-Minute Telegram 68-2023-3/3

  • Background: Colonoscopy is recommended after a positive stool-based test (SBT) for colorectal cancer (CRC) screening. This study investigated the rates of and factors associated with follow-up colonoscopy (FU-CY) after a positive SBT.
  • Study population: 32,769 primary care patients aged 50–70 years with an average risk of CRC and a positive SBT
  • Methods: retrospective analysis of anonymized electronic health records
  • Main results
    • FU-CY was performed within 360 days of a positive SBT in 56.1% of patients.
    • White patients were more likely to have FU-CY than Black patients (HR, 0.85; 95% CI, 0.80–0.91) or Asian patients (0.79; 0.69–0.91).
    • Individuals with commercial insurance were more likely to have FU-CY than those with Medicare (0.95; 0.91–0.99) or Medicaid (0.79; 0.73–0.85).
    • Patients tested with multitarget stool DNA tests were more likely to have FU-CY than those who had a fecal immunochemical test (1.63; 1.57–1.68).
    • FU-CY rates were lower in 2020 than in 2019, which the authors attribute to the COVID-19 pandemic.
  • Limitations include:
    • Analysis of electronic health records data may have led to confounding.
    • Generalizability to other populations is limited.

The take-home message?

In this large retrospective study, FU-CY occurred less frequently than recommended, especially among Black and Asian patients, those with noncommercial insurance, and those who had a fecal immunochemical test. Physicians screening for CRC should be aware of this potential gap in care to help prevent complications and mortality related to delayed diagnosis and treatment of CRC.

  • AMBOSS links: Kolorektales Karzinom | Kolonpolypen
  • Original study: Rates of follow-up colonoscopy after a positive stool-based screening test result for colorectal cancer among health care organizations in the US, 2017-2020 [61]
  • Authors: Mohl JT, Ciemins EL, Miller-Wilson L et al.
  • Journal: JAMA Netw Open
  • Study funding: Exact Sciences Corporation

Edition 67 - January 28, 2023toggle arrow icon

Freezing the progression of atrial fibrillation

One-Minute Telegram 67-2023-1/3

  • Background: Paroxysmal atrial fibrillation (AF) frequently progresses to persistent AF, [62] which is associated with higher rates of thromboembolism, heart failure, and health care utilization. Early cryoablation therapy reduces the recurrence of atrial tachyarrhythmias within the first year of treatment compared to antiarrhythmic drug therapy. [63] This follow-up analysis set out to determine whether early cryoablation has longer-term disease-modifying benefits.
  • Study population: 303 patients with untreated paroxysmal AF
  • Methods: multicenter, open-label randomized trial
    • Rhythm control therapy with cryoballoon ablation (n = 154) or antiarrhythmic drug therapy (n = 149)
    • Cardiac events were recorded using implantable loop recorders.
    • Follow-up: 3 years
  • Main results (intention-to-treat analysis)
    • Episodes of persistent AF (lasting > 7 days or lasting > 48 hours and requiring cardioversion)
      • Ablation group: 1.9%
      • Antiarrhythmic drug group: 7.4%
      • HR, 0.25; 95% CI, 0.09–0.70
    • Recurrent atrial tachyarrhythmia (lasting ≥ 30 seconds)
      • Ablation group: 56.5%
      • Antiarrhythmic drug group: 77.2%
      • HR, 0.51; 0.38–0.67
    • Hospitalization
      • Ablation group: 5.2%
      • Antiarrhythmic drug group: 16.8%
      • Relative risk, 0.31; 0.14–0.66
    • Trend toward lower risk of serious adverse events in the ablation group (RR, 0.45; 0.19–1.05)
  • Limitations include:
    • 18 patients crossed over to the ablation group after unsuccessful medical therapy.
    • Outcomes may not be generalizable to other ablation techniques.

The take-home message?

Over a 3-year follow-up, patients with paroxysmal AF treated with early cryoballoon ablation had lower rates of progression to persistent AF, recurrent atrial tachyarrhythmia, and hospitalization compared to patients treated with antiarrhythmic drug therapy. Larger trials are required to assess whether cryoballoon ablation can also reduce rates of stroke, heart failure, and death in this patient population.

  • AMBOSS links: Vorhofflimmern
  • Original study: Progression of atrial fibrillation after cryoablation or drug therapy [64]
  • Authors: Andrade JG et al.
  • Journal: NEJM
  • Study funding: Cardiac Arrhythmia Network of Canada and others

Empagliflozin improves outcomes in chronic kidney disease

One-Minute Telegram 67-2023-2/3

  • Background: SGLT2 inhibitors reduce the risk of chronic kidney disease (CKD) progression in patients with proteinuric CKD and type 2 diabetes. [65][66] This study set out to assess the effects of empagliflozin on a diverse group of patients with CKD, including those without diabetes or proteinuria.
  • Study population: 6609 adults with CKD (mean age 63.8 years; 33.2% women; 54% without diabetes) with an estimated glomerular filtration rate (eGFR) of 20–45 mL/min/1.73 m2, regardless of albuminuria, or an eGFR of 45–90 mL/min/1.73 m2 and a urinary albumin:creatinine ratio ≥ 200 mg/g
  • Methods: double-blind randomized controlled trial
  • Main results
    • Primary outcome: progression of CKD or death from cardiovascular causes
      • Empagliflozin group: 13.1%
      • Placebo group: 16.9%
      • HR, 0.72; 95% CI, 0.64–0.82
      • No significant differences across eGFR subgroups nor between patients with or without diabetes
    • Secondary outcomes
      • Lower rate of hospitalization in the empagliflozin group (HR, 0.86; 0.78–0.95)
      • No difference in all-cause mortality or composite of heart failure hospitalizations and cardiovascular death
    • Similar rates of serious adverse events between groups
  • Limitations include: A low number of cardiovascular events may have reduced the statistical power for the assessment of secondary outcomes.

The take-home message?

Patients with CKD treated with empagliflozin had lower rates of CKD progression or cardiovascular mortality than those who received placebo, regardless of diabetes status or eGFR subgroup.

Fluvoxamine: no panacea for COVID-19

One-Minute Telegram 67-2023-3/3

  • Background: A recent metaanalysis suggests that fluvoxamine, a selective serotonin reuptake inhibitor with antiinflammatory effects, can reduce COVID-19-related hospitalizations. [68][69] However, high-quality randomized studies demonstrating a benefit with fluvoxamine for the treatment of COVID-19 have so far been lacking.
  • Study population: 1288 patients ≥ 30 years of age (mean age 47 years; 57% female) with mild-to-moderate COVID-19 with > 2 symptoms for < 7 days
  • Methods: randomized controlled adaptive platform trial [70]
    • Fluvoxamine (50 mg; n = 674) or placebo (n = 614) twice daily for 10 days
    • Follow-up: 28 days
  • Main results
    • Primary outcome: median time to recovery (3 consecutive symptom-free days)
      • Fluvoxamine group: 12 days (IQR, 11–14 days)
      • Placebo group: 13 days (IQR, 12–13 days)
      • HR, 0.96; 95% credible interval, 0.86–1.06
    • Secondary outcome: composite of hospitalization, urgent care or ED visit, or death
      • Fluvoxamine group: 3.8%
      • Placebo group: 3.9%
      • HR, 1.1; 0.5–1.8
    • Similar rates of adverse events and duration of symptoms in both groups
  • Limitations include:
    • Study likely underpowered to detect a difference in secondary outcome because of the low number of clinical events in both groups
    • Significant delay from symptom onset to treatment initiation (median: 5 days)

The take-home message?

In this RCT, fluvoxamine did not improve clinical outcomes in patients with mild-to-moderate COVID-19 compared to placebo.

  • AMBOSS links: COVID-19
  • Original study: Effect of fluvoxamine vs placebo on time to sustained recovery in outpatients with mild to moderate COVID-19: a randomized clinical trial [71]
  • Authors: McCarthy MW et al.
  • Journal: JAMA
  • Study funding: National Center for Advancing Translational Sciences

Edition 66 - January 14, 2023toggle arrow icon

2021 AHA/ACC model overestimates the risk of coronary artery disease

One-Minute Telegram 66-2023-1/3

  • Background: Pretest probability (PTP) models for obstructive coronary artery disease (CAD) include the European Society of Cardiology PTP (ESC-PTP) model, risk factor-weighted clinical likelihood (RF-CL) model, and the 2021 American Heart Association/American College of Cardiology PTP (AHA/ACC-PTP) model. [72][73][74] The aim of this study was to determine whether PTP models that categorize chest pain (ESC-PTP and RF-CL) and/or include additional risk factors (RF-CL) are more accurate than the AHA/ACC-PTP.
  • Study population: 50,561 patients (mean age 57.3 years, 54% female) with symptoms suggestive of obstructive CAD, without previously diagnosed CAD, receiving first-time coronary computed tomography angiography (CCTA)
  • Methods: multicenter cohort study between 2008 and 2019
    • Invasive coronary angiography (ICA) was performed based on CCTA results and standard clinical practice.
    • Prevalence of obstructive CAD was determined using ICA.
    • AHA/ACC-PTP, ESC-PTP, and RF-CL were calculated and compared.
  • Main results
    • Obstructive CAD prevalence: 8.0%
    • Median predicted prevalence of obstructive CAD
      • AHA/ACC-PTP: 16% (95% CI, 13–32%)
      • ESC-PTP: 11% (6–19%)
      • RF-CL: 5% (2–11%)
    • RF-CL had the highest accuracy (P < 0.001)
    • AHA/ACC-PTP had lower accuracy in predicting prevalence of CAD than ESC-PTP (P < 0.001).
    • AHA/ACC-PTP model overestimated the prevalence of CAD by a factor of 2.6 (2.6–2.7); overestimation was highest (factor of 4.8) in patients with nonanginal pain.
  • Limitations include:
    • Limited generalizability of results
      • Patients in the database used were predominantly White.
      • Patients with severe kidney disease and arrhythmias or severe obesity were not included.
    • Risk of selection bias: All participants had been referred for CTA, which excluded very low-risk patients.

The take-home message?

The AHA/ACC-PTP model significantly overestimated the prevalence of obstructive CAD. Models that include risk factors for CAD and symptom characteristics have the highest accuracy and may reduce unnecessary testing in patients with a low PTP of obstructive CAD. Care should be taken in generalizing these results to populations not included in this study.

  • AMBOSS links: Akutes Koronarsyndrom | Koronare Herzkrankheit
  • Original study: Performance of the American Heart Association/American College of Cardiology guideline-recommended pretest probability model for the diagnosis of obstructive coronary artery disease [75]
  • Authors: Winther S et al.
  • Journal: JAHA
  • Study funding: Novo Nordisk Foundation

Chlorthalidone and hydrochlorothiazide: not so different after all

One-Minute Telegram 66-2023-2/3:

  • Background: Chlorthalidone (CTD) is the preferred thiazide diuretic antihypertensive according to the 2017 ACC/AHA hypertension guidelines, [76] but recent research has shown that hydrochlorothiazide (HCTZ) may have similar efficacy to CTD in preventing cardiovascular disease (CVD) events, with a lower risk of adverse events. [77] This study compared the effect of CTD vs. HCTZ on the risk of major CVD events.
  • Study population: 13,523 adults in the Veterans Affairs Healthcare System ≥ 65 years of age receiving HCTZ for hypertension (mean age 72 years, 97% male, 15% Black)
  • Methods: multicenter, pragmatic, open-label trial (median follow-up 2.4 years)
    • Patients were randomized to either remain on HCTZ (25 mg or 50 mg) or switch to CTD (12.5 mg or 25 mg).
    • Primary outcome: composite of non-cancer-related deaths and nonfatal CVD events, e.g., myocardial infarction (MI) or stroke
    • Secondary outcomes: individual components of primary outcome
    • Safety outcomes include electrolyte abnormalities, hospitalization, and acute kidney injury.
  • Main results
    • No between-group differences in primary outcome (HR, 1.04; 95% CI, 0.94–1.16) or secondary outcomes
    • Hypokalemia: 6.0% in the CTD group, 4.4% in the HCTZ group (HR, 1.38; 1.19–1.60)
    • Subgroup analyses
      • Incidence of the primary outcome was lower with CTD than with HCTZ in patients with previous MI and/or stroke (14.3% vs. 19.4%).
      • Incidence of the primary outcome was higher with CTD than with HCTZ in patients without previous MI or stroke (9.9% vs. 8.9%).
  • Limitations include:
    • Open-label design may have influenced adherence and testing frequency.
    • Results may not be applicable to higher doses of CTD or HCTZ.
    • Generalizability: Study population was 97% male.

The take-home message?

Patients with hypertension receiving HCTZ had a similar risk of CVD events and non-cancer-related death compared to patients receiving CTD at 2.4 years follow-up. Care should be taken in generalizing these results to higher medication doses and patients with a history of a major CVD event.

I would walk 5000 steps, but should I walk 5000 more?

One-Minute Telegram 66-2023-3/3:

  • Background: The oft-cited recommendation to take 10,000 steps/day originated as a marketing campaign, not from the scientific literature. The aim of this trial was to assess whether daily step count is associated with the risk of cardiovascular disease (CVD) events.
  • Study population: 20,152 adults ≥ 18 years of age (mean age 63 years, 52% female, > 70% non-Hispanic White)
  • Methods: metaanalysis of 8 prospective studies (mean follow-up 6.2 years)
    • Study requirements: device-measured steps and follow-up for CVD events
    • Step volume: average steps per day over a single 3–7-day period
    • Primary outcome: first subsequent CVD event (stroke, coronary artery disease, heart failure) stratified by sex and age
  • Main results
    • In participants ≥ 60 years of age, 6000–9000 steps/day was associated with an approx. 50% lower risk of CVD events compared to 2000 steps/day (HR, 0.51; 95% CI, 0.41–0.63).
    • In adults < 60 years of age, steps/day was not associated with risk of CVD events.
    • There were no subgroup differences in risk of CVD events by sex.
  • Limitations include:
    • Potential for residual confounding and reverse causality
    • Follow-up period may not have been long enough to capture benefits of higher steps/day in young adults.

The take-home message?

Higher steps/day were associated with a lower risk of CVD events than lower steps/day in adults ≥ 60 years of age. Benefits also began with step counts well below the widely promoted 10,000 steps/day.

Quellentoggle arrow icon

  1. Fang, Selvin:Cost-Related Insulin Rationing in US Adults Younger Than 65 Years With DiabetesIn: JAMA. 2023, doi: 10.1001/jama.2023.5747 . | Open in Read by QxMD.
  2. Lenze et al.:Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric DepressionIn: New England Journal of Medicine. Band: 388, Nummer: 12, 2023, doi: 10.1056/nejmoa2204462 . | Open in Read by QxMD p. 1067-1079.
  3. Skinner et al.:Marriage, Children, and Sex-Based Differences in Physician Hours and IncomeIn: JAMA Health Forum. Band: 4, Nummer: 3, 2023, doi: 10.1001/jamahealthforum.2023.0136 . | Open in Read by QxMD p. e230136.
  4. Barry et al.:Preexposure Prophylaxis to Prevent Acquisition of HIVIn: JAMA. Band: 330, Nummer: 8, 2023, doi: 10.1001/jama.2023.14461 . | Open in Read by QxMD p. 736.
  5. Chen, Chen:Accuracy of Chatbots in Citing Journal ArticlesIn: JAMA Network Open. Band: 6, Nummer: 8, 2023, doi: 10.1001/jamanetworkopen.2023.27647 . | Open in Read by QxMD p. e2327647.
  6. Li et al.:Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trialIn: The Lancet. Band: 402, Nummer: 10405, 2023, doi: 10.1016/s0140-6736(23)01240-0 . | Open in Read by QxMD p. 851-858.
  7. Lincoff et al.:Cardiovascular Safety of Testosterone-Replacement TherapyIn: New England Journal of Medicine. Band: 389, Nummer: 2, 2023, doi: 10.1056/nejmoa2215025 . | Open in Read by QxMD p. 107-117.
  8. Thompson et al.:Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trialIn: BMJ. 2023, doi: 10.1136/bmj-2023-075230 . | Open in Read by QxMD p. e075230.
  9. Rigotti et al.:Cytisinicline for Smoking CessationIn: JAMA. Band: 330, Nummer: 2, 2023, doi: 10.1001/jama.2023.10042 . | Open in Read by QxMD p. 152.
  10. Mangione et al.:Screening for Skin CancerIn: JAMA. Band: 329, Nummer: 15, 2023, doi: 10.1001/jama.2023.4342 . | Open in Read by QxMD p. 1290.
  11. Santos et al.:Quality-of-Life and Recurrence Outcomes Following Laparoscopic Elective Sigmoid Resection vs Conservative Treatment Following DiverticulitisIn: JAMA Surgery. 2023, doi: 10.1001/jamasurg.2023.0466 . | Open in Read by QxMD.
  12. Dorsch et al.:A Computable Algorithm for Medication Optimization in Heart Failure With Reduced Ejection FractionIn: JACC: Advances. 2023, doi: 10.1016/j.jacadv.2023.100289 . | Open in Read by QxMD p. 100289.
  13. Knuuti et al.:2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromesIn: European Heart Journal. 2019, doi: 10.1093/eurheartj/ehz425 . | Open in Read by QxMD.
  14. Winther et al.:Incorporating Coronary Calcification Into Pre-Test Assessment of the Likelihood of Coronary Artery DiseaseIn: Journal of the American College of Cardiology. Band: 76, Nummer: 21, 2020, doi: 10.1016/j.jacc.2020.09.585 . | Open in Read by QxMD p. 2421-2432.
  15. Gulati et al.:2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest PainIn: Journal of the American College of Cardiology. Band: 78, Nummer: 22, 2021, doi: 10.1016/j.jacc.2021.07.053 . | Open in Read by QxMD p. e187-e285.
  16. Winther et al.:Performance of the American Heart Association/American College of Cardiology Guideline‐Recommended Pretest Probability Model for the Diagnosis of Obstructive Coronary Artery DiseaseIn: Journal of the American Heart Association. Band: 11, Nummer: 24, 2022, doi: 10.1161/jaha.122.027260 . | Open in Read by QxMD.
  17. Whelton et al.:2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice GuidelinesIn: Hypertension. Band: 71, Nummer: 6, 2018, doi: 10.1161/hyp.0000000000000066 . | Open in Read by QxMD p. 1269-1324.
  18. Hripcsak et al.:Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat HypertensionIn: JAMA Internal Medicine. Band: 180, Nummer: 4, 2020, doi: 10.1001/jamainternmed.2019.7454 . | Open in Read by QxMD p. 542.
  19. Ishani et al.:Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular EventsIn: New England Journal of Medicine. Band: 387, Nummer: 26, 2022, doi: 10.1056/nejmoa2212270 . | Open in Read by QxMD p. 2401-2410.
  20. Paluch et al.:Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-AnalysisIn: Circulation. Band: 147, Nummer: 2, 2023, doi: 10.1161/circulationaha.122.061288 . | Open in Read by QxMD p. 122-131.
  21. Shapiro et al.:Early Restrictive or Liberal Fluid Management for Sepsis-Induced HypotensionIn: New England Journal of Medicine. Band: 388, Nummer: 6, 2023, doi: 10.1056/nejmoa2212663 . | Open in Read by QxMD p. 499-510.
  22. Vasilevskis et al.:Deprescribing Medications Among Older Adults From End of Hospitalization Through Postacute CareIn: JAMA Internal Medicine. 2023, doi: 10.1001/jamainternmed.2022.6545 . | Open in Read by QxMD.
  23. Pittas et al.:Vitamin D and Risk for Type 2 Diabetes in People With PrediabetesIn: Annals of Internal Medicine. 2023, doi: 10.7326/m22-3018 . | Open in Read by QxMD.
  24. Grinspoon et al.:Pitavastatin to Prevent Cardiovascular Disease in HIV InfectionIn: New England Journal of Medicine. 2023, doi: 10.1056/nejmoa2304146 . | Open in Read by QxMD.
  25. Shaikh et al.:Identifying Children Likely to Benefit From Antibiotics for Acute SinusitisIn: JAMA. Band: 330, Nummer: 4, 2023, doi: 10.1001/jama.2023.10854 . | Open in Read by QxMD p. 349.
  26. Copaescu et al.:Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin AllergyIn: JAMA Internal Medicine. 2023, doi: 10.1001/jamainternmed.2023.2986 . | Open in Read by QxMD.
  27. Thiele et al.:Extracorporeal Life Support in Infarct-Related Cardiogenic ShockIn: New England Journal of Medicine. 2023, doi: 10.1056/nejmoa2307227 . | Open in Read by QxMD.
  28. Sleem et al.:Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular DiseaseIn: JAMA Cardiology. 2023, doi: 10.1001/jamacardio.2023.3364 . | Open in Read by QxMD.
  29. Gunst et al.:Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICUIn: New England Journal of Medicine. Band: 389, Nummer: 13, 2023, doi: 10.1056/nejmoa2304855 . | Open in Read by QxMD p. 1180-1190.
  30. Shaish et al.:Diagnostic Accuracy of Unenhanced Computed Tomography for Evaluation of Acute Abdominal Pain in the Emergency DepartmentIn: JAMA Surgery. 2023, doi: 10.1001/jamasurg.2023.1112 . | Open in Read by QxMD p. e231112.
  31. Mangione et al.:Screening for Latent Tuberculosis Infection in AdultsIn: JAMA. Band: 329, Nummer: 17, 2023, doi: 10.1001/jama.2023.4899 . | Open in Read by QxMD p. 1487.
  32. Young et al.:Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid WithdrawalIn: New England Journal of Medicine. 2023, doi: 10.1056/nejmoa2214470 . | Open in Read by QxMD.
  33. Meaidi et al.:Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort studyIn: BMJ. 2023, doi: 10.1136/bmj-2022-074450 . | Open in Read by QxMD p. e074450.
  34. Nam et al.:Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic StrokeIn: JAMA. Band: 330, Nummer: 9, 2023, doi: 10.1001/jama.2023.14590 . | Open in Read by QxMD p. 832.
  35. Biscaglia et al.:Complete or Culprit-Only PCI in Older Patients with Myocardial InfarctionIn: New England Journal of Medicine. Band: 389, Nummer: 10, 2023, doi: 10.1056/nejmoa2300468 . | Open in Read by QxMD p. 889-898.
  36. Papi et al.:Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older AdultsIn: New England Journal of Medicine. Band: 388, Nummer: 7, 2023, doi: 10.1056/nejmoa2209604 . | Open in Read by QxMD p. 595-608.
  37. Mangione et al.:Serologic Screening for Genital Herpes InfectionIn: JAMA. Band: 329, Nummer: 6, 2023, doi: 10.1001/jama.2023.0057 . | Open in Read by QxMD p. 502.
  38. Full et al.:Sleep Irregularity and Subclinical Markers of Cardiovascular Disease: The Multi‐Ethnic Study of AtherosclerosisIn: Journal of the American Heart Association. Band: 12, Nummer: 4, 2023, doi: 10.1161/jaha.122.027361 . | Open in Read by QxMD.
  39. Miah et al.:Dexamethasone versus Surgery for Chronic Subdural HematomaIn: New England Journal of Medicine. Band: 388, Nummer: 24, 2023, doi: 10.1056/nejmoa2216767 . | Open in Read by QxMD p. 2230-2240.
  40. Schrag et al.:Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With CancerIn: JAMA. Band: 329, Nummer: 22, 2023, doi: 10.1001/jama.2023.7843 . | Open in Read by QxMD p. 1924.
  41. Huang et al.:Efficacy of Continuous Transdermal Nitroglycerin for Treating Hot Flashes by Inducing Nitrate Cross-tolerance in Perimenopausal and Postmenopausal WomenIn: JAMA Internal Medicine. 2023, doi: 10.1001/jamainternmed.2023.1977 . | Open in Read by QxMD.
  42. Blue et al.:Effects of the Million Hearts Model on Myocardial Infarctions, Strokes, and Medicare SpendingIn: JAMA. Band: 330, Nummer: 15, 2023, doi: 10.1001/jama.2023.19597 . | Open in Read by QxMD p. 1437.
  43. Donovan et al.:Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive AdultsIn: New England Journal of Medicine. Band: 389, Nummer: 15, 2023, doi: 10.1056/nejmoa2216218 . | Open in Read by QxMD p. 1357-1367.
  44. Reed et al.:Telemedicine Versus In-Person Primary Care: Treatment and Follow-up VisitsIn: Annals of Internal Medicine. Band: 176, Nummer: 10, 2023, doi: 10.7326/m23-1335 . | Open in Read by QxMD p. 1349-1357.
  45. Paton et al.:Treatment Strategy for Rifampin-Susceptible TuberculosisIn: New England Journal of Medicine. Band: 388, Nummer: 10, 2023, doi: 10.1056/nejmoa2212537 . | Open in Read by QxMD p. 873-887.
  46. Hong et al.:Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery DiseaseIn: JAMA. 2023, doi: 10.1001/jama.2023.2487 . | Open in Read by QxMD.
  47. Dhayat et al.:Hydrochlorothiazide and Prevention of Kidney-Stone RecurrenceIn: New England Journal of Medicine. Band: 388, Nummer: 9, 2023, doi: 10.1056/nejmoa2209275 . | Open in Read by QxMD p. 781-791.
  48. O’Toole et al.:Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a FractureIn: New England Journal of Medicine. Band: 388, Nummer: 3, 2023, doi: 10.1056/nejmoa2205973 . | Open in Read by QxMD p. 203-213.
  49. Mentz et al.:Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart FailureIn: JAMA. Band: 329, Nummer: 3, 2023, doi: 10.1001/jama.2022.23924 . | Open in Read by QxMD p. 214.
  50. Mohl et al.:Rates of Follow-up Colonoscopy After a Positive Stool-Based Screening Test Result for Colorectal Cancer Among Health Care Organizations in the US, 2017-2020In: JAMA Network Open. Band: 6, Nummer: 1, 2023, doi: 10.1001/jamanetworkopen.2022.51384 . | Open in Read by QxMD p. e2251384.
  51. Padfield et al.:Progression of paroxysmal to persistent atrial fibrillation: 10-year follow-up in the Canadian Registry of Atrial FibrillationIn: Heart Rhythm. Band: 14, Nummer: 6, 2017, doi: 10.1016/j.hrthm.2017.01.038 . | Open in Read by QxMD p. 801-807.
  52. Andrade et al.:Cryoablation or Drug Therapy for Initial Treatment of Atrial FibrillationIn: New England Journal of Medicine. 2020, doi: 10.1056/nejmoa2029980 . | Open in Read by QxMD.
  53. Andrade et al.:Progression of Atrial Fibrillation after Cryoablation or Drug TherapyIn: New England Journal of Medicine. Band: 388, Nummer: 2, 2023, doi: 10.1056/nejmoa2212540 . | Open in Read by QxMD p. 105-116.
  54. Heerspink et al.:Dapagliflozin in Patients with Chronic Kidney DiseaseIn: New England Journal of Medicine. 2020, doi: 10.1056/nejmoa2024816 . | Open in Read by QxMD.
  55. Perkovic et al.:Canagliflozin and Renal Outcomes in Type 2 Diabetes and NephropathyIn: New England Journal of Medicine. 2019, doi: 10.1056/nejmoa1811744 . | Open in Read by QxMD.
  56. The EMPA-KIDNEY Collaborative Group:Empagliflozin in Patients with Chronic Kidney DiseaseIn: New England Journal of Medicine. 2022, doi: 10.1056/nejmoa2204233 . | Open in Read by QxMD.
  57. Lee et al.:Fluvoxamine for Outpatient Management of COVID-19 to Prevent HospitalizationIn: JAMA Network Open. Band: 5, Nummer: 4, 2022, doi: 10.1001/jamanetworkopen.2022.6269 . | Open in Read by QxMD p. e226269.
  58. Rosen et al.:Modulation of the sigma-1 receptor–IRE1 pathway is beneficial in preclinical models of inflammation and sepsisIn: Science Translational Medicine. Band: 11, Nummer: 478, 2019, doi: 10.1126/scitranslmed.aau5266 . | Open in Read by QxMD.
  59. Park et al.:An overview of platform trials with a checklist for clinical readersIn: Journal of Clinical Epidemiology. Band: 125, 2020, doi: 10.1016/j.jclinepi.2020.04.025 . | Open in Read by QxMD p. 1-8.
  60. McCarthy et al.:Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19In: JAMA. Band: 329, Nummer: 4, 2023, doi: 10.1001/jama.2022.24100 . | Open in Read by QxMD p. 296.
  61. Deligiannidis et al.:Zuranolone for the Treatment of Postpartum DepressionIn: American Journal of Psychiatry. 2023, doi: 10.1176/appi.ajp.20220785 . | Open in Read by QxMD.
  62. Ishigami et al.:Effects of Cuff Size on the Accuracy of Blood Pressure ReadingsIn: JAMA Internal Medicine. 2023, doi: 10.1001/jamainternmed.2023.3264 . | Open in Read by QxMD.
  63. Sims et al.:Donanemab in Early Symptomatic Alzheimer DiseaseIn: JAMA. Band: 330, Nummer: 6, 2023, doi: 10.1001/jama.2023.13239 . | Open in Read by QxMD p. 512.
  64. Barry et al.:Screening for Hypertensive Disorders of PregnancyIn: JAMA. Band: 330, Nummer: 11, 2023, doi: 10.1001/jama.2023.16991 . | Open in Read by QxMD p. 1074.
  65. Chambers et al.:Buprenorphine Dose and Time to Discontinuation Among Patients With Opioid Use Disorder in the Era of FentanylIn: JAMA Network Open. Band: 6, Nummer: 9, 2023, doi: 10.1001/jamanetworkopen.2023.34540 . | Open in Read by QxMD p. e2334540.
  66. Kosiborod et al.:Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and ObesityIn: New England Journal of Medicine. 2023, doi: 10.1056/nejmoa2306963 . | Open in Read by QxMD.
  67. Levkovich, Elyoseph:Identifying depression and its determinants upon initiating treatment: ChatGPT versus primary care physiciansIn: Family Medicine and Community Health. Band: 11, Nummer: 4, 2023, doi: 10.1136/fmch-2023-002391 . | Open in Read by QxMD p. e002391.
  68. Ehrmann et al.:Inhaled Amikacin to Prevent Ventilator-Associated PneumoniaIn: New England Journal of Medicine. 2023, doi: 10.1056/nejmoa2310307 . | Open in Read by QxMD.
  69. Levine et al.:Adult Attention-Deficit/Hyperactivity Disorder and the Risk of DementiaIn: JAMA Network Open. Band: 6, Nummer: 10, 2023, doi: 10.1001/jamanetworkopen.2023.38088 . | Open in Read by QxMD p. e2338088.
  70. Dequin et al.:Hydrocortisone in Severe Community-Acquired PneumoniaIn: New England Journal of Medicine. 2023, doi: 10.1056/nejmoa2215145 . | Open in Read by QxMD.
  71. Baker et al.:Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a SulfonylureaIn: JAMA Network Open. Band: 6, Nummer: 3, 2023, doi: 10.1001/jamanetworkopen.2023.3646 . | Open in Read by QxMD p. e233646.
  72. Hamdy et al.:Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate CancerIn: New England Journal of Medicine. 2023, doi: 10.1056/nejmoa2214122 . | Open in Read by QxMD.
  73. Barnett et al.:Racial Inequality in Receipt of Medications for Opioid Use DisorderIn: New England Journal of Medicine. Band: 388, Nummer: 19, 2023, doi: 10.1056/nejmsa2212412 . | Open in Read by QxMD p. 1779-1789.
  74. Lampert et al.:Vigorous Exercise in Patients With Hypertrophic CardiomyopathyIn: JAMA Cardiology. 2023, doi: 10.1001/jamacardio.2023.1042 . | Open in Read by QxMD.
  75. Caraballo et al.:Excess Mortality and Years of Potential Life Lost Among the Black Population in the US, 1999-2020In: JAMA. Band: 329, Nummer: 19, 2023, doi: 10.1001/jama.2023.7022 . | Open in Read by QxMD p. 1662.
  76. Barry et al.:Screening for Anxiety Disorders in AdultsIn: JAMA. Band: 329, Nummer: 24, 2023, doi: 10.1001/jama.2023.9301 . | Open in Read by QxMD p. 2163.
  77. Barry et al.:Screening for Depression and Suicide Risk in AdultsIn: JAMA. Band: 329, Nummer: 23, 2023, doi: 10.1001/jama.2023.9297 . | Open in Read by QxMD p. 2057.
  78. Rosenstock et al.:Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous InsulinIn: New England Journal of Medicine. 2023, doi: 10.1056/nejmoa2303208 . | Open in Read by QxMD.
  79. Nissen et al.:Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant PatientsIn: JAMA. Band: 330, Nummer: 2, 2023, doi: 10.1001/jama.2023.9696 . | Open in Read by QxMD p. 131.

Icon of a lockNoch 3 weitere Kapitel kostenfrei zugänglich

Du kannst diesen Monat noch 3 Kapitel kostenfrei aufrufen. Melde dich jetzt an, um unbegrenzten Zugang zu erhalten.
 Evidenzbasierte Inhalte, von festem ärztlichem Redaktionsteam erstellt & geprüft. Disclaimer aufrufen.