Reinterpreted Genetic Tests

In this episode of Annals On Call, Dr. Centor discusses the obligation of physicians to follow up with patients no longer in their care when genetic test interpretation changes with Dr. Paul Appelbaum. First, listen to the podcast. After listening, ACP members can take the CME/MOC quiz for free.

Recurrent Atrial Fibrillation: The “Why?” and “When?” of “What to Do?"

The Annals Consult Guys discuss the care of a patient with 2 symptomatic episodes of atrial fibrillation who is currently in sinus rhythm.

Real-World Complications of Lung Cancer Screening

In this episode of Annals On Call, Dr. Centor discusses the real-world complications of lung cancer screening with Drs. Katharine A. Rendle and Anil Vachani. First, listen to the podcast. After listening, ACP members can take the CME/MOC quiz for free.

Raising Money from Patients? What’s a Physician to Do?

Physicians often are not trained about or aware of the ethical implications of raising money from patients. This gap can lead to a number of ethical concerns. In this case study, the authors examine the implications for the patient-physician relationship and physician professionalism, patient confidentiality, implications for community-institution relationships, and the importance of physician leadership.

Radiation Oncology Side Effects: 5 Pearls Segment

Though therapeutic radiation is a common intervention among cancer patients, with up to 50% of all cancer patients receiving some form of radiation therapy, understanding of radiation therapy among generalists remains an unmet need. Medical school curricula commonly include the basic underlying mechanisms of chemotherapy, but the physiology and role of radiation therapy is often unaddressed (or remains a limited/optional module).

R2D2

Clinicians are often expected to utilize clinical decision support systems. However, they receive little to no training in the actual use of such systems.

QI Curriculum Step 4: Implement and Sustain Change

In Step 4 of ACP’s four-part Quality Improvement (QI) curriculum, you will focus on how to consider what changes to try, study the results of trials of those changes, and identify improvements to adopt and sustain. Developed by physicians for physicians and their clinical teams, this online training series guides you through each stage of the QI journey.

QI Curriculum Step 3: Plan for Change and Identify Solutions

In Step 3 of ACP’s four-part Quality Improvement (QI) curriculum, you will determine the major causes contributing to the issues at hand and identify solutions to address these causes. Developed by physicians for physicians and their clinical teams, this online training series guides you through each stage of the QI journey.

QI Curriculum Step 2: Identify How to Measure Change

In Step 2 of ACP’s four-part Quality Improvement (QI) curriculum, you will learn strategies for selecting metrics and for measuring change at each stage of the QI process. Developed by physicians for physicians and their clinical teams, this online training series guides you through each stage of the QI journey.

QI Curriculum Step 1: Establish the What and Why for Change

In Step 1 of ACP’s four-part Quality Improvement (QI) curriculum, you will establish what needs to change and identify the reasons why change is necessary. Developed by physicians for physicians and their clinical teams, this online training series guides you through each stage of the QI journey. It is part of a broader ACP initiative designed to empower and engage physicians in meaningful QI programs that result in meaningful and sustained change.

Cost-Effectiveness of First- and Second-Step Treatment Strategies for Major Depressive Disorder: A Rapid Review: Annals of Internal Medicine: Vol 176, No 2

Background: Major depressive disorder (MDD) is the most prevalent, disabling form of depression, with a high economic effect. Purpose: To assess evidence on cost-effectiveness of pharmacologic and nonpharmacologic interventions as first- and second-step treatments in patients with MDD. Data Sources: Multiple electronic databases limited to English language were searched (1 January 2015 to 29 November 2022). Study Selection: Two investigators independently screened the literature. Seven economic modeling studies fulfilled the eligibility criteria. Data Extraction: Data abstraction by a single investigator was confirmed by a second; 2 investigators independently rated risk of bias. One investigator determined certainty of evidence, and another checked for plausibility. Data Synthesis: Seven modeling studies met the eligibility criteria. In a U.S. setting over a 5-year time horizon, cognitive behavioral therapy (CBT) was cost-effective compared with second-generation antidepressants (SGAs) as a first-step treatment from the societal and health care sector perspectives. However, the certainty of evidence is low, and the findings should be interpreted cautiously. For second-step treatment, only switch strategies between SGAs were assessed. The evidence is insufficient to draw any conclusions. Limitations: Methodologically heterogeneous studies, which compared only CBT and some SGAs, were included. No evidence on other psychotherapies or complementary and alternative treatments as first-step treatment or augmentation strategies as second-step treatment was available. Conclusion: Although CBT may be cost-effective compared with SGAs as a first-step treatment at a 5-year time horizon from the societal and health care sector perspectives, the certainty of evidence is low, and the findings need to be interpreted cautiously. For other comparisons, the evidence was entirely missing or insufficient to draw conclusions. Primary Funding Source: American College of Physicians.

Participant Recruitment From Low- and Middle-Income Countries for Pivotal Trials of Drugs Approved by the U.S. Food and Drug Administration: A Cross-Sectional Analysis: Annals of Internal Medicine: Vol 175, No 12

Background: Many participants in clinical trials supporting U.S. Food and Drug Administration (FDA) drug approvals are recruited from outside the United States, including from low- and middle-income countries (LMICs). Where participants are recruited for pivotal trials has implications for ethical research conduct and generalizability. Objective: To describe LMIC recruitment for pivotal trials of newly approved drugs for cancer, neurologic disease, and cardiovascular disease. Design: Cross-sectional analysis. Setting: Pivotal trials of new cancer, cardiovascular, and neurologic drugs approved from 2012 to 2019 matched to ClinicalTrials.gov, FDA records, and publications. Measurements: Host countries and available per country enrollments were extracted. The primary end point was the proportion of pivotal trials enrolling participants in LMICs. The secondary end point was the proportion of pivotal trial participants contributed by LMICs for each indication area. Results: Data were obtained from 66 new drugs and 144 pivotal clinical trials. All cardiovascular approvals (12 drugs, 29 trials) and neurologic approvals (26 drugs, 54 trials) were analyzed, as well as a random sample of cancer approvals (28 of 85 drugs [33%]) matched to their pivotal trials (61 of 210 trials [29%]). Among the trials, 56% in cancer, 79% in cardiovascular disease, and 56% in neurology recruited from an LMIC. For multicountry trials, country-level enrollment figures were not available for 71 trials (55%). For those reporting per country enrollment, the percentage of participants recruited from LMICs was 8% for cancer trials, 36% for cardiovascular trials, and 17% for neurology trials. Limitations: The study was limited to FDA-approved drugs in 3 areas, including a sample of cancer drugs. Pivotal trials of nonapproved drugs or drugs for other indications were not captured. Conclusion: Most pivotal trials for FDA-approved drugs recruit from LMICs. Publications and FDA documents generally do not provide country-level data on recruitment. Primary Funding Source: None.

Effectiveness of mRNA COVID-19 Vaccine Boosters Against Infection, Hospitalization, and Death: A Target Trial Emulation in the Omicron (B.1.1.529) Variant Era

Background: The effectiveness of a third mRNA COVID-19 vaccine dose (booster dose) against the Omicron (B.1.1.529) variant is uncertain, especially in older, high-risk populations. Objective: To determine mRNA booster vaccine effectiveness (VE) against SARS-CoV-2 infection, hospitalization, and death in the Omicron era by booster type, primary vaccine type, time since primary vaccination, age, and comorbidity burden. Design: Retrospective matched cohort study designed to emulate a target trial of booster vaccination versus no booster, conducted from 1 December 2021 to 31 March 2022. Setting: U.S. Department of Veterans Affairs health care system. Participants: Persons who had received 2 mRNA COVID-19 vaccine doses at least 5 months earlier. Intervention: Booster monovalent mRNA vaccination (Pfizer–BioNTech's BNT162b2 or Moderna's mRNA-1273) versus no booster. Measurements: Booster VE. Results: Each group included 490 838 well-matched persons, who were predominantly male (88%), had a mean age of 63.0 years (SD, 14.0), and were followed for up to 121 days (mean, 79.8 days). Booster VE more than 10 days after a booster dose was 42.3% (95% CI, 40.6% to 43.9%) against SARS-CoV-2 infection, 53.3% (CI, 48.1% to 58.0%) against SARS-CoV-2–related hospitalization, and 79.1% (CI, 71.2% to 84.9%) against SARS-CoV-2–related death. Booster VE was similar for different booster types (BNT162b2 or mRNA-1273), age groups, and primary vaccination regimens but was significantly higher with longer time since primary vaccination and higher comorbidity burden. Limitation: Predominantly male population. Conclusion: Booster mRNA vaccination was highly effective in preventing death and moderately effective in preventing infection and hospitalization for up to 4 months after administration in the Omicron era. Increased uptake of booster vaccination, which is currently suboptimal, should be pursued to limit the morbidity and mortality of SARS-CoV-2 infection, especially in persons with high comorbidity burden. Primary Funding Source: U.S. Department of Veterans Affairs.

Nonpharmacologic and Pharmacologic Treatments of Adult Patients With Major Depressive Disorder: A Systematic Review and Network Meta-analysis for a Clinical Guideline by the American College of Physicians

An update is available for this article. Background: Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD). Purpose: To compare the benefits and harms of nonpharmacologic treatments with second-generation antidepressants as first-step interventions for acute MDD, and to compare second-step treatment strategies for patients who did not achieve remission after an initial attempt with antidepressants. Data Sources: English-language studies from several electronic databases from 1 January 1990 to 8 August 2022, trial registries, gray literature databases, and reference lists to identify unpublished research. Study Selection: 2 investigators independently selected randomized trials of at least 6 weeks' duration. Data Extraction: Reviewers abstracted data about study design and conduct, participants, interventions, and outcomes. They dually rated the risk of bias of studies and the certainty of evidence for outcomes of interest. Data Synthesis: 65 randomized trials met the inclusion criteria; eligible data from nonrandomized studies were not found. Meta-analyses and network meta-analyses indicated similar benefits of most nonpharmacologic treatments and antidepressants as first-step treatments. Antidepressants had higher risks for discontinuation because of adverse events than most other treatments. For second-step therapies, different switching and augmentation strategies provided similar symptomatic relief. The certainty of evidence for most comparisons is low; findings should be interpreted cautiously. Limitations: Many studies had methodological limitations or dosing inequalities; publication bias might have affected some comparisons. In some cases, conclusions could not be drawn because of insufficient evidence. Conclusion: Although benefits seem to be similar among first- and second-step MDD treatments, the certainty of evidence is low for most comparisons. Clinicians and patients should focus on options with the most reliable evidence and take adverse event profiles and patient preferences into consideration. Primary Funding Source: American College of Physicians. (PROSPERO: CRD42020204703)

Rugers, Remingtons, and Reality: A Gun Lover's Plea for a Safer Second Amendment

Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 176, No 1

Background: It remains unclear if a low-carbohydrate, high-fat (LCHF) diet is a possible treatment strategy for type 2 diabetes mellitus (T2DM), and the effect on nonalcoholic fatty liver disease (NAFLD) has not been investigated. Objective: To investigate the effect of a calorie-unrestricted LCHF diet, with no intention of weight loss, on T2DM and NAFLD compared with a high-carbohydrate, low-fat (HCLF) diet. Design: 6-month randomized controlled trial with a 3-month follow-up. (ClinicalTrials.gov: NCT03068078) Setting: Odense University Hospital in Denmark from November 2016 until June 2020. Participants: 165 participants with T2DM. Intervention: Two calorie-unrestricted diets: LCHF diet with 50 to 60 energy percent (E%) fat, less than 20E% carbohydrates, and 25E% to 30E% proteins and HCLF diet with 50E% to 60E% carbohydrates, 20E% to 30E% fats, and 20E% to 25E% proteins. Measurements: Glycemic control, serum lipid levels, metabolic markers, and liver biopsies to assess NAFLD. Results: The mean age was 56 years (SD, 10), and 58% were women. Compared with the HCLF diet, participants on the LCHF diet had greater improvements in hemoglobin A1c (mean difference in change, −6.1 mmol/mol [95% CI, −9.2 to −3.0 mmol/mol] or −0.59% [CI, −0.87% to −0.30%]) and lost more weight (mean difference in change, −3.8 kg [CI, −6.2 to −1.4 kg]). Both groups had higher high-density lipoprotein cholesterol and lower triglycerides at 6 months. Changes in low-density lipoprotein cholesterol were less favorable in the LCHF diet group than in the HCLF diet group (mean difference in change, 0.37 mmol/L [CI, 0.17 to 0.58 mmol/L] or 14.3 mg/dL [CI, 6.6 to 22.4 mg/dL]). No statistically significant between-group changes were detected in the assessment of NAFLD. Changes were not sustained at the 9-month follow-up. Limitation: Open-label trial, self-reported adherence, unintended weight loss, and lack of adjustment for multiple comparisons. Conclusion: Persons with T2DM on a 6-month, calorie-unrestricted, LCHF diet had greater clinically meaningful improvements in glycemic control and weight compared with those on an HCLF diet, but the changes were not sustained 3 months after intervention. Primary Funding Source: Novo Nordisk Foundation.

Comparison of Over-the-Scope Clips to Standard Endoscopic Treatment as the Initial Treatment in Patients With Bleeding From a Nonvariceal Upper Gastrointestinal Cause: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 176, No 4

Background: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined. Objective: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes. Design: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395) Setting: University teaching hospitals in Hong Kong, China, and Australia. Patients: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. Intervention: Standard hemostatic treatment (n = 97) or OTSC (n = 93). Measurements: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization. Results: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, −0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]). Limitation: Clinicians were not blinded to treatment and the option of crossover treatment. Conclusion: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement. Primary Funding Source: General Research Fund to the University Grant Committee, Hong Kong SAR Government.

Effectiveness of an Unsupervised Online Yoga Program on Pain and Function in People With Knee Osteoarthritis: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 175, No 10

Background: Yoga is a mind–body exercise typically done in groups in person, but this delivery method can be inconvenient, inaccessible, and costly. Effective online programs may increase access to exercise for knee osteoarthritis. Objective: To evaluate the effectiveness of an unsupervised 12-week online yoga program. Design: Two-group superiority randomized trial. (Australian New Zealand Clinical Trials Registry: ACTRN12620000012976) Setting: Community. Participants: 212 adults with symptomatic knee osteoarthritis. Intervention: Both groups received online osteoarthritis information (control). The yoga group also received access to an unsupervised online yoga program delivered via prerecorded videos over 12 weeks (1 video per week, with each session to be performed 3 times per week), with optional continuation thereafter. Measurements: Primary outcomes were changes in knee pain during walking (0 to 10 on a numerical rating scale) and physical function (0 to 68 on the Western Ontario and McMaster Universities Osteoarthritis Index) at 12 weeks (primary time point) and 24 weeks, analyzed using mixed-effects linear regression models. Secondary outcomes were self-reported overall knee pain, stiffness, depression, anxiety, stress, global change, quality of life, self-efficacy, fear of movement, and balance confidence. Adverse events were also collected. Results: A total of 195 (92%) and 189 (89%) participants provided 12- and 24-week primary outcomes, respectively. Compared with control at 12 weeks, yoga improved function (between-group mean difference in change, −4.0 [95% CI, −6.8 to −1.3]) but not knee pain during walking (between-group mean difference in change, −0.6 [CI, −1.2 to 0.1]), with more yoga participants than control participants achieving the minimal clinically important difference (MCID) for both outcomes. At 12 weeks, knee stiffness, quality of life, and arthritis self-efficacy improved more with yoga than the control intervention. Benefits were not maintained at 24 weeks. Adverse events were minor. Limitation: Participants were unblinded. Conclusion: Compared with online education, an unsupervised online yoga program improved physical function but not knee pain at 12 weeks in people with knee osteoarthritis, although the improvement did not reach the MCID and was not sustained at 24 weeks. Primary Funding Source: National Health and Medical Research Council and Centres of Research Excellence.

Major Update 2: Antibody Response and Risk for Reinfection After SARS-CoV-2 Infection—Final Update of a Living, Rapid Review

Background: The durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear. Purpose: To synthesize evidence on the SARS-CoV-2 antibody response and reinfection risk with a focus on gaps identified in our prior reports. Data Sources: MEDLINE (Ovid), EMBASE, CINAHL, World Health Organization Research Database, and reference lists from 16 December 2021 through 8 July 2022, with surveillance through 22 August 2022. Study Selection: English-language, cohort studies evaluating IgG antibody duration at least 12 months after SARS-CoV-2 infection, the antibody response among immunocompromised adults, predictors of nonseroconversion, and reinfection risk. Data Extraction: Two investigators sequentially extracted study data and rated quality. Data Synthesis: Most adults had IgG antibodies after SARS-CoV-2 infection at time points greater than 12 months (low strength of evidence [SoE]). Although most immunocompromised adults develop antibodies, the overall proportion with antibodies is lower compared with immunocompetent adults (moderate SoE for organ transplant patients and low SoE for patients with cancer or HIV). Prior infection provided substantial, sustained protection against symptomatic reinfection with the Delta variant (high SoE) and reduced the risk for severe disease due to Omicron variants (moderate SoE). Prior infection was less protective against reinfection with Omicron overall (moderate SoE), but protection from earlier variants waned rapidly (low SoE). Limitation: Single review for abstract screening and sequential review for study selection, data abstraction, and quality assessment. Conclusion: Evidence for a sustained antibody response to SARS-CoV-2 infection is considerable for both Delta and Omicron variants. Prior infection protected against reinfection with both variants, but, for Omicron, protection was weaker and waned rapidly. This information may have limited clinical applicability as new variants emerge. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098)

Assessment of the Risk Evaluation and Mitigation Strategy (REMS) for Phentermine–Topiramate to Prevent Exposure During Pregnancy

Background: The U.S. Food and Drug Administration approved phentermine–topiramate for obesity in 2012 and required a Risk Evaluation and Mitigation Strategy (REMS) to prevent prenatal exposure. No such requirement was introduced for topiramate. Objective: To evaluate the rate of prenatal exposure, contraceptive use, and pregnancy testing among patients with phentermine–topiramate compared with topiramate or other antiobesity medications (AOMs). Design: Retrospective cohort study. Setting: Nationwide health insurance claims database. Participants: Females aged 12 to 55 years with no infertility diagnosis or sterilization procedure. Patients with other indications for topiramate were excluded to identify a cohort that was likely treated for obesity. Measurements: Patients initiated use of phentermine–topiramate, topiramate, or an AOM (liraglutide, lorcaserin, or bupropion–naltrexone). Pregnancy at treatment initiation, conception during treatment, contraceptive use, and pregnancy testing outcomes were ascertained. Measurable confounders were adjusted for, and extensive sensitivity analyses were done. Results: A total of 156 280 treatment episodes were observed. Adjusted prevalence of pregnancy at treatment initiation was 0.9 versus 1.6 per 1000 episodes (prevalence ratio, 0.54 [95% CI, 0.31 to 0.95]) for phentermine–topiramate versus topiramate. The incidence rate of conception during treatment was 9.1 versus 15.0 per 1000 person-years (rate ratio, 0.61 [CI, 0.40 to 0.91]) for phentermine–topiramate versus topiramate. Both outcomes were similarly lower for phentermine–topiramate compared with AOM. Prenatal exposure was marginally lower in topiramate users compared with AOM users. Approximately 20% of patients in all cohorts had at least 50% of treatment days covered by contraceptives. Few patients had pregnancy tests before treatment (≤5%), but this was more common among phentermine–topiramate users. Limitations: Outcome misclassification; unmeasured confounding due to lack of prescriber data to account for possible clustering and spillover effects. Conclusion: Prenatal exposure seemed to be significantly lower among phentermine–topiramate users under the REMS. Pregnancy testing and contraceptive use appeared to be inadequate for all groups, which deserves attention to prevent the remaining potential exposures. Primary Funding Source: None.

Calcium, vitamin D may affect long-term health in postmenopausal women

Put words in our mouth

Registration is open for ACP's live online POCUS Mentorship Program

Clinical Skills Center programs to offer hands-on and interactive learning opportunities

New COVID-19 vaccine recommendations, data on after-effects of infection

MKSAP Quiz: Runner evaluation during a marathon

Recommendations released on statin therapy for people with HIV

Bariatric surgery improves long-term diabetes outcomes more than medication, lifestyle interventions

Support, empathy, system changes vital to battling burnout

Recruiting, retaining rural physicians

Use of decision aid in ED for patients with AF linked to decrease in admissions | ACP Hospitalist

Severity criteria for categorizing COPD exacerbations validated as prognostic tool | ACP Hospitalist

Critical care experts propose expanding definition of ARDS | ACP Hospitalist

Considering ketamine | ACP Hospitalist

Catheters recalled; warning on troponin tests | ACP Hospitalist

Readmission, mortality rates high for hospitalized HF patients worldwide | ACP Hospitalist

Pushing back on physical restraints | ACP Hospitalist

Procedure committee set standards for measuring residents' competence | ACP Hospitalist

Long-term doxycycline may reduce exacerbations for some COPD patients | ACP Hospitalist

IDSA updates guidance on managing drug-resistant, gram-negative infections | ACP Hospitalist