A Qualitative Evidence Synthesis of Patient and Provider Attitudes Toward Audio-Only Telemental Health Care.

Background: Audio-only (phone) telemental health care can increase access to care, but its lack of nonverbal information may negatively impact care quality as compared to video or in-person visits. The objective of this work was to understand patient and provider attitudes toward phone care via a review of qualitative research. Methods: A qualitative evidence synthesis was conducted of peer-reviewed qualitative research published between 2013 and 2023. Studies were required to include qualitative data regarding patient and/or provider attitudes toward audio-only telemental health care. Results pertinent to phone care were extracted and underwent coding followed by theme identification. Results: We identified 2,065 abstracts and 29 articles were ultimately included in the synthesis; 27 of these studies were conducted during the COVID-19 pandemic. Five themes described benefits of phone care, nine described drawbacks, and three themes were neutral. Phone care was seen as easy to use, particularly for briefer check-ins or as a back-up option if video calls failed, and some patients preferred the privacy of not being seen. However, the loss of visual information during phone visits was considered particularly challenging in the treatment of more complex or severe patients; providers questioned whether they were able to provide high quality care, and patients reported feeling less supported and understood by their providers. Conclusions: The relative benefits and drawbacks of audio-only telemental health care must be carefully weighed against the options of video or in-person treatment based on patient needs and severity. Future work should continue to examine patient and provider attitudes toward phone care as the mental health landscape evolves postpandemic.

Frequency and preventability of adverse drug events in the outpatient setting.

BACKGROUND: Limited data exist regarding adverse drug events (ADEs) in the outpatient setting. The objective of this study was to determine the incidence, severity, and preventability of ADEs in the outpatient setting and identify potential prevention strategies. METHODS: We conducted an analysis of ADEs identified in a retrospective electronic health records review of outpatient encounters in 2018 at 13 outpatient sites in Massachusetts that included 13 416 outpatient encounters in 3323 patients. Triggers were identified in the medical record including medications, consultations, laboratory results, and others. If a trigger was detected, a further in-depth review was conducted by nurses and adjudicated by physicians to examine the relevant information in the medical record. Patients were included in the study if they were at least 18 years of age with at least one outpatient encounter with a physician, nurse practitioner or physician's assistant in that calendar year. Patients were excluded from the study if the outpatient encounter occurred in outpatient surgery, psychiatry, rehabilitation, and paediatrics. RESULTS: In all, 5% of patients experienced an ADE over the 1-year period. We identified 198 ADEs among 170 patients, who had a mean age of 60. Most patients experienced one ADE (87%), 10% experienced two ADEs and 3% experienced three or more ADEs. The most frequent drug classes resulting in ADEs were cardiovascular (25%), central nervous system (14%), and anti-infective agents (14%). Severity was ranked as significant in 85%, 14% were serious, 1% were life-threatening, and there were no fatal ADEs. Of the ADEs, 22% were classified as preventable and 78% were not preventable. We identified 246 potential prevention strategies, and 23% of ADEs had more than one prevention strategy possibility. CONCLUSIONS: Despite efforts to prioritise patient safety, medication-related harms are still frequent. These results underscore the need for further patient safety improvement in the outpatient setting.

A Calculated Risk: Evaluation of QTc Drug-Drug Interaction (DDI) Clinical Decision Support (CDS) Alerts and Performance of the Tisdale Risk Score Calculator.

INTRODUCTION: A risk factor for a potentially fatal ventricular arrhythmia Torsade de Pointes is a prolongation in the heart rate-corrected QT interval (QTc) ≥ 500 milliseconds (ms) or an increase of ≥ 60 ms from a patient's baseline value, which can cause sudden cardiac death. The Tisdale risk score calculator uses clinical variables to predict which hospitalized patients are at the highest risk for QTc prolongation. OBJECTIVE: To determine the rate of overridden QTc drug-drug interaction (DDI)-related clinical decision support (CDS) alerts per patient admission and the prevalence by Tisdale risk score category of these overridden alerts. Secondary outcome was to determine the rate of drug-induced QTc prolongation (diQTP) associated with overrides. METHODS: Our organization's enterprise data warehouse was used to retrospectively access QTc DDI alerts presented for patients aged ≥ 18 years who were admitted to Brigham and Women's Hospital during 2022. The QTc DDI CDS alerts were included if shown to a physician, fellow, resident, physician assistant, or nurse practitioner when entering the order in inpatient areas for patients with a length of stay of at least 2 days. Variables collected for the Tisdale calculator included age, sex, whether patient was on a loop diuretic, potassium level, admission QTc value, admitting diagnosis of acute myocardial infarction, sepsis, or heart failure, and number of QTc-prolonging drugs given to the patient. RESULTS: A total of 2649 patients with 3033 patient admissions had 18,432 QTc DDI alerts presented that were overridden. An average of 3 unique QTc DDI alerts were presented per patient admission and the alerts were overridden an average of 6 times per patient admission. Overall, 6% of patient admissions were low risk (score ≤ 6), 64% moderate risk (score 7-10), and 30% high risk (score ≥ 11) of QTc prolongation. The most common QTc DDI alerts overridden resulting in an diQTP were quetiapine and propofol (11%) and amiodarone and haloperidol (7%). The diQTP occurred in 883 of patient admissions (29%) and was more frequent in those with higher risk score, with 46% of patient admissions with diQTP in high risk, 23% in moderate risk, and 8% in low risk. CONCLUSION: Use of the Tisdale calculator to assess patient-specific risk of QT prolongation combined with CDS may improve overall alert quality and acceptance rate, which may decrease the diQTP rate.

Effectiveness of a Population Health Intervention on Disparities in Hypertension Control: A Stepped Wedge Cluster Randomized Clinical Trial.

BACKGROUND: Disparities in hypertension control across race, ethnicity, and language have been a long-standing problem in the United States. OBJECTIVE: To assess whether a multi-pronged intervention can improve hypertension control for a target population and reduce disparities. DESIGN: This stepped wedge cluster randomized trial was conducted at 15 adult primary care clinics affiliated with Massachusetts General Hospital. PCPs were randomized to receive the intervention in twelve groups. PARTICIPANTS: The target population was patients who met one of the following criteria based on self-identification: (1) Asian, Black, Indigenous, multi-racial, or other race; (2) Hispanic ethnicity; or (3) preferred language other than English. Reference population was White, English-speaking patients. INTERVENTIONS: PCPs were given access to an online equity dashboard that displays disparities in chronic disease management and completed an equity huddle with population health coordinators (PHCs), which involved reviewing target patients whose hypertension was not well controlled. In addition, community health workers (CHWs) were available in some practices to offer additional support. MAIN MEASURES: The primary outcome was change in the proportion of target patients meeting the hypertension control goal when comparing intervention and control periods. KEY RESULTS: Of the 365 PCPs who were randomized, 311 PCPs and their 10,865 target patients were included in the analysis. The intervention led to an increase in hypertension control in the target population (RD 0.9%; 95% CI [0.3,1.5]) and there was a higher intervention effect in the target population compared to the reference population (DiD 2.1%; 95% CI [1.1, 3.1]). CONCLUSIONS: Utilizing data on disparities in quality outcome measures in routine clinical practice augmented by clinical support provided by PHCs and CHWs led to modest, but statistically significant, improvement in hypertension control among BIPOC, Hispanic, and LEP patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05278806.

Changes in Metabolic Parameters of Hemoglobin A1c, Weight, and Blood Pressure During and After COVID-19 Stay-at-Home Orders.

BACKGROUND: Due to the COVID-19 pandemic, a "state of emergency" was declared in North Carolina on March 10, 2020. Subsequent "stay-at-home" (SAH) orders restricted activities including use of fitness facilities, and teleworking was encouraged. This study investigates metabolic effects of these changes in activity level. METHODS: This retrospective prepost study included adults diagnosed with type 2 diabetes mellitus and hypertension with hemoglobin A1c (HbA1c), weight, and blood pressure (BP) measurements for 3 time periods: 3/10/2019-9/9/2019 ("pre-SAH"), 3/10/2020-9/9/2020 ("during SAH"), and 3/10/2021-9/9/2021 ("post-SAH"). The primary outcome was change in HbA1c pre-SAH to during SAH and during SAH to post-SAH. Secondary outcomes were changes in weight, systolic BP (SBP), and diastolic BP (DBP) over the same periods. Exploratory outcomes included health care utilization. Paired t test compared outcomes between time periods using Bonferroni-adjusted α of 0.025 for significance. RESULTS: Analysis included 301 participants with an average age of 69.8 years. HbA1c, SBP, and DBP trended up from pre-SAH to during SAH and then decreased post-SAH with a significant change only for DBP from during SAH to post-SAH (74.2 mmHg to 73.6 mmHg, P < .001). Weight trended down across the 3 study periods. In-office visits significantly decreased from pre-SAH to during SAH, and telehealth visits significantly decreased from during SAH to post-SAH (both P < .001). CONCLUSIONS: With the exception of DBP, findings reveal consistency in HbA1c, weight, and BP across time periods before, during, and after COVID-19 SAH orders in North Carolina.

The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Precise control of protein ubiquitination is essential for brain development, and hence, disruption of ubiquitin signaling networks can lead to neurological disorders. Mutations of the deubiquitinase USP7 cause the Hao-Fountain syndrome (HAFOUS), characterized by developmental delay, intellectual disability, autism, and aggressive behavior. Here, we report that conditional deletion of USP7 in excitatory neurons in the mouse forebrain triggers diverse phenotypes including sensorimotor deficits, learning and memory impairment, and aggressive behavior, resembling clinical features of HAFOUS. USP7 deletion induces neuronal apoptosis in a manner dependent of the tumor suppressor p53. However, most behavioral abnormalities in USP7 conditional mice persist despite p53 loss. Strikingly, USP7 deletion in the brain perturbs the synaptic proteome and dendritic spine morphogenesis independently of p53. Integrated proteomics analysis reveals that the neuronal USP7 interactome is enriched for proteins implicated in neurodevelopmental disorders and specifically identifies the RNA splicing factor Ppil4 as a novel neuronal substrate of USP7. Knockdown of Ppil4 in cortical neurons impairs dendritic spine morphogenesis, phenocopying the effect of USP7 loss on dendritic spines. These findings reveal a novel USP7-Ppil4 ubiquitin signaling link that regulates neuronal connectivity in the developing brain, with implications for our understanding of the pathogenesis of HAFOUS and other neurodevelopmental disorders.

Use of Cardioprotective Antidiabetic Medications in Adults With and Without Cardiovascular Disease, 2015 to March 2020.

BACKGROUND: Certain glucagon-like peptide-1 receptor (GLP-1) agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2-inhibitors) can reduce cardiovascular risk in individuals with type 2 diabetes and cardiovascular disease (CVD). However, these medications can be expensive, potentially limiting their use. Objectives: The primary objective was to characterize the use of cardioprotective GLP-1 agonists and SGLT2-inhibitors among adults with diabetes with and without CVD. The secondary objective was to investigate the association of socioeconomic factors and health care utilization with the use of these medications. METHODS: Adults aged ≥20 years old with self-reported diabetes, A1c ≥6.5%, or fasting glucose ≥126 mg/dL were identified using the 2015 to March 2020 National Health and Nutrition Examination Survey. The primary outcome was the use of cardioprotective GLP-1 agonists or SGLT2-inhibitors compared in individuals with and without CVD. Secondary analyses included identification of socioeconomic factors and health care utilization associated with the use of cardioprotective antidiabetic medications, stratified by CVD status. Weighted analyses were conducted to account for the complex survey design. RESULTS: Use of cardioprotective antidiabetic medications was higher in adults with CVD compared to those without CVD (7.8% vs. 4.6%, P = 0.02), which was driven by the use of cardioprotective SGLT2-inhibitors (4.6% versus 1.9%, P = 0.002). Lower income level and less frequent health care visits within the past year were associated with lower likelihood of using these medications. CONCLUSION AND RELEVANCE: Despite preferential use in individuals with diabetes and CVD, the prevalence of cardioprotective antidiabetic medication use remains relatively low. Disparities in use appear to exist based on income level and health care utilization.

What We Have Learned About Combining a Ketogenic Diet and Chemoimmunotherapy: a Case Report and Review of Literature.

Background: A high-fat, moderate-protein, low-carbohydrate ketogenic diet has been reported in the literature as a treatment option for patients with cancer. Case Presentation: A 69-year-old veteran was initially diagnosed with stage III colorectal cancer and progressed to having liver, pancreatic, and omental lymph node involvement despite completing adjuvant FOLFOX (fluorouracil, leucovorin calcium, and oxaliplatin) after surgery. The patient was treated with FOLFIRI (fluorouracil, leucovorin calcium, and irinotecan hydrochloride) and bevacizumab, followed by encorafenib and cetuximab on progression. Subsequently, he received pembrolizumab but continued to progress. The patient was later placed on trifluridine/tipiracil and bevacizumab concurrent with a ketogenic diet. Positron emission tomography and carcinoembryonic antigen levels indicated disease stabilization for 10 months. On progression, the patient was transitioned to ipilumimab and nivolumab and continued to adhere to the ketogenic diet. The patient's disease has continued to remain stable for the past 1 year. His degree of ketosis was determined using the glucose ketone index. The patient continues to have a good quality of life during concurrent ketogenic diet and therapy. Conclusions: This case supports the tolerability of the ketogenic diet along with chemotherapy and immunotherapy and should be considered as an adjunct to standard cancer treatment. In this report, we reviewed the latest literature about cellular mechanism of the ketogenic diet and the efficacy and relationship with chemotherapy and immunotherapy. We are about to open a ketogenic diet protocol at the Veterans Affairs Central California Health Care System in Fresno.

Targeted Treatment of Adults with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Tafasitamab in Context.

The outcomes of Relapsed/Refractory (R/R) Diffuse Large B-cell lymphoma have been historically poor. The recent development of several novel therapies including CD19 directed agents has improved the prognosis of this disease significantly. Chimeric antigen receptor (CAR) T-cell therapy has drastically changed the treatment of R/R DLBCL, but it is still associated with significant barriers and limited access. Tafasitamab (an anti-CD19 engineered monoclonal antibody), in addition to lenalidomide, has shown significant efficacy with exceptionally durable responses in patients with R/R DLBCL who are ineligible for autologous stem cell transplantation (ASCT). Tafasitamab-lenalidomide and certain other therapies (ie, antibody-drug conjugates and bispecific antibodies) are important treatment options for patients who are ineligible for CAR-T due to co-morbidities or lack of access, and patients with rapid progression of disease who are unable to wait for manufacturing of CAR-T. This review will thus discuss currently approved and recently studied targeted treatment options for patients with R/R DLBCL with an emphasis on CAR-T alternative options, particularly Tafasitamab-lenalidomide.

Evaluation of the change in glycated hemoglobin for patients in an employee health program formerly managed by a pharmacist-run ambulatory care clinic.

PURPOSE: To evaluate the change in mean glycated hemoglobin (HbA1c) for patients with diabetes in an employee health program after discontinuation of management by a clinical pharmacist. METHODS: This was a single-center, retrospective chart review of patients followed by a clinical pharmacist from January 1, 2020, through March 31, 2021. Patients included had type 2 diabetes, were 18 years of age or older, were not pregnant, and were not using an insulin pump. The baseline visit was defined as the last pharmacist visit within the study period. The follow-up visit was defined as the most recent visit upon chart review that occurred at least 5 months after the baseline visit. The primary and secondary endpoints were the mean change in HbA1c and number of antihyperglycemic agents from baseline to follow-up, respectively. Statistical analysis included descriptive statistics for baseline characteristics, a paired t test for the primary endpoint, and a McNemar test for the secondary endpoint. RESULTS: A total of 590 patients were screened, of whom 131 were included in the analysis. For the primary outcome, the mean baseline HbA1c was 7.3% while that at follow-up was 7.41% (mean change of 0.11%; SD, 1.22%; P = 0.326). For the secondary outcome, the baseline number of antihyperglycemic agents was 274 while the follow-up number was 276. There were no statistically significant differences for the primary and secondary outcomes. CONCLUSION: This study highlights a unique patient population with controlled HbA1c at baseline, for whom diabetes control may potentially be influenced by the patients' employment within a healthcare system and improved access to care. The lack of a significant difference in the primary endpoint implies that it may be appropriate to limit or have less frequent pharmacist visits for well-controlled patients. Further research should investigate how to identify patients who would benefit from continued follow-up with a clinical pharmacist vs those who can be managed with minimal resources.

Association between mental health and self-care behavior among older adults with diabetes according to Behavioral Risk Factor Surveillance System 2019.

AIM: To assess the association of mental health burden with diabetes-related self-care behaviors and healthcare utilization among older adults. METHOD: This cross-sectional 2019 Behavioral Risk Factor Surveillance System (BRFSS) study included ≥ 65 years old adults with self-reported diabetes. Three groups were used based on the number of days in the past month affected by mental health: 0 days (no burden), 1-13 days (occasional burden), and 14-30 days (frequent burden). Primary outcome was performing ≥ 3 of 5 diabetes-related self-care behaviors. Secondary outcome was performing ≥ 3 of 5 healthcare utilization behaviors. Multivariable logistic regression was used in Stata/SE 15.1. RESULTS: Of 14,217 included individuals, 10.2 % reported frequent mental health burden. Compared to 'no burden', 'occasional' and 'frequent burden' groups included more female, obese, not married persons with younger age of diabetes diagnosis, and reported more comorbidities, insulin use, cost-related barriers to see doctors, and diabetes-related eye issues (p < 0.05). 'Occasional/frequent burden' groups reported less self-care and healthcare utilization behaviors, except 30 % higher healthcare utilization was observed in the 'occasional burden' group compared to no burden (aOR 1.30, 95 %CI 1.08-1.58, p = 0.006). CONCLUSIONS: Overall, mental health burden was associated with reduced participation in diabetes-related self-care and healthcare utilization behaviors in a stepwise manner, except occasional burden was associated with higher healthcare utilization.

Implementation of pharmacist recommendations in patients with type 2 diabetes enrolled in an employer-sponsored health plan.

BACKGROUND: The new, employee health plan (EHP) focused, population health initiative was established at Atrium Health Wake Forest Baptist in October 2020. The initiative's goals are to reduce health care costs and optimize patient care by providing patient-specific recommendations to help manage chronic disease states in the ambulatory care setting. This project's purpose is to quantify and categorize pharmacist recommendations implemented and not implemented. OBJECTIVE: Describe the implementation of pharmacist recommendations in a new, population health program. METHODS: Eligible patients: >18 years of age, diagnosed with type 2 diabetes, baseline HbA1c > 8%, and enrolled in the EHP. Patients were identified retrospectively through an electronic health record report. The primary endpoint assessed the proportion of pharmacist recommendations implemented. Interventions implemented and not implemented were categorized and reviewed for timely optimization of patient care and quality improvement. RESULTS: Overall, 55.7% of pharmacist recommendations were implemented. The most common reason recommendations were not implemented was that they were not addressed by the provider. The most common pharmacist recommendation was a drug therapy addition. Recommendations were implemented in a median time of 44 days. CONCLUSION: Over half of pharmacist recommendations were implemented. Provider communication and awareness was identified as a barrier for this new initiative. Increasing provider education and advertisement of pharmacist services should be considered to increase future implementation rates. The project identified a need for optimization of timely patient care by prioritizing patient charts prior to their next applicable provider visit.

Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice.

OBJECTIVE: The objective of this article was to review pharmacology, efficacy, safety, and place in therapy of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. DATA SOURCES: PubMed/MEDLINE and ClinicalTrials.gov were searched through September 7, 2022, using the keyword "tirzepatide." STUDY SELECTION AND DATA EXTRACTION: Clinical trials with available results were included. DATA SYNTHESIS: Seven published phase 3, multicenter, randomized, parallel-group trials investigated efficacy and safety of tirzepatide versus placebo, semaglutide, insulin degludec, and insulin glargine for type 2 diabetes mellitus (T2DM) treatment. Studies included adults with uncontrolled T2DM and body mass index above 23 or 25 kg/m2. Hemoglobin A1c reduction from baseline was greater with tirzepatide across all studies with absolute reductions up to 3.02% and relative reductions ranging 0.44% (vs semaglutide) to 2.11% (vs placebo). Weight loss was significant. Incidence of gastrointestinal adverse effects (AE) was similar to semaglutide, and major cardiovascular events was similar to insulin glargine. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Studies demonstrated greater A1c lowering and weight reduction versus placebo and active comparators with AE similar to semaglutide, suggesting tirzepatide will be a valuable addition to the growing list of antidiabetic medications. Although tirzepatide's effects on major cardiovascular events was not increased when compared with insulin glargine, further evidence is needed to assess long-term implications on cardiovascular outcomes compared with agents with proven cardiovascular benefits. CONCLUSIONS: Tirzepatide has the potential to significantly impact the clinical management of T2DM, and results of ongoing clinical trials will help to fully determine its place in therapy.

Racial and ethnic differences in blood pressure before and after the 2016 United States general election.

OBJECTIVES: The 2016 U.S. presidential election was a major source of stress among many adults. Psychosocial stress can manifest physiologically in elevated blood pressure (BP). Little is known regarding the association of macro-level sociopolitical events with BP changes at the population-level. This study sought to characterize population-level changes in BP following the 2016 U.S. presidential election. METHODS: Using 2015-2018 National Health and Nutrition Examination Survey, we included participants aged ≥18 years during the same periods prior to (May to October 2015/2016) and after (May to October 2017/2018) the election. Survey-weighted data were analyzed to compare population-level systolic BP (SBP) and diastolic BP (DBP) pre- and post-election, stratified by race/ethnicity. Sex differences were also investigated. RESULTS: We observed significant increases in SBP among non-Hispanic (NH) Asian participants (+3.4 mmHg; p = .046), but not among other racial/ethnic participants. DBP increased among NH Black participants (+2.3 mmHg; p = .049) and Mexican American participants (+2.9 mmHg; p = .007), but not among other racial/ethnic participants. These changes appeared attributable to differential BP changes by sex. CONCLUSIONS: At the population-level, variable changes in BP were observed by race/ethnicity following the 2016 U.S. presidential election, possibly driven by SBP elevations among women.

Prescribing Patterns of Antihypertensive Agents and Blood Pressure Control Among Patients With Incident Stage 2 Hypertension.

Background: Initiation of appropriate antihypertensive therapy is crucial, particularly among patients with stage 2 hypertension, whom initiation of dual antihypertensive agents is suggested. Little is known regarding real-world prescribing of antihypertensive agents for patients with incident stage 2 hypertension. Objective: The primary objective was to describe prescribing patterns of antihypertensive therapy among patients with incident stage 2 hypertension. The secondary objectives included determining association of blood pressure (BP) control with initial multiple antihypertensive agents. Methods: Retrospective cohort analysis was conducted using electronic medical records from 6 primary care clinics between January 2014 and June 2019. Included patients were ≥18 years with an initial diagnosis of stage 2 hypertension, defined as BP ≥160/100 mm Hg Primary analysis was characterizing prescribing patterns of antihypertensive agents among patients with incident stage 2 hypertension. Investigation of BP control (<140/90 mm Hg) at 3 months of diagnosis was also performed. Results: We identified 261 patients with incident stage 2 hypertension (mean age, 52 years; 53.2% males; mean baseline BP, 162.1/100.1 mm Hg). Approximately 72% of patients were initiated on single antihypertensive agent, with the most common being angiotensin receptor blockers (ARBs; 25.7%) and angiotensin-converting-enzyme (ACE) inhibitors (24.6%). Commonly initiated multiple antihypertensive agents were ACE-inhibitor + thiazide-like diuretic (52.7%), followed by an ARB + thiazide-like diuretic (21.6%). Multiple antihypertensive therapy was associated with improved BP control at 3 months (adjusted odds ratio [OR], 3.54; 95% confidence interval [CI], 1.55-8.06). Conclusion: Majority of patients with incident stage 2 hypertension were prescribed initial single antihypertensive therapy, though better BP control at 3 months was seen among those initiated on multi-antihypertensive therapy.

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management.

OBJECTIVE: To review the pharmacology, efficacy, and safety of high-dose once-weekly semaglutide for chronic weight management. DATA SOURCES: PubMed/MEDLINE and ClinicalTrials.gov were searched (inception to September 8, 2021) using keywords "semaglutide" and "obesity," "weight," "high dose," "high-dose," or "2.4." STUDY SELECTION AND DATA EXTRACTION: Clinical trials with published results were included. Publications studying the oral or <2.4 mg formulation of semaglutide were excluded. DATA SYNTHESIS: Four phase 3, multicenter, randomized, double-blind trials demonstrated efficacy of high-dose once-weekly semaglutide compared with placebo for weight loss. Study populations included patients with overweight or obesity (STEP 1, STEP 3, and STEP 4) or patients with diabetes and with overweight or obesity (STEP 2). Lifestyle interventions for diet and exercise were included for all participants. Weight loss from baseline was significant for all studies, and secondary outcomes demonstrated cardiometabolic improvements including waist circumference, systolic blood pressure, and lipid profiles. Gastrointestinal adverse effects were common, but the medication was otherwise well tolerated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: High-dose semaglutide offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors and glycemic indices. Clinicians and patients should consider the route and frequency of administration, adverse effect profile, and cost when choosing an antiobesity medication. The importance of concomitant lifestyle interventions should be emphasized. CONCLUSIONS: High-dose once-weekly semaglutide can significantly reduce weight, and although gastrointestinal adverse effects were common, it is generally well tolerated.

Primary Duodenal Periampullary Adenocarcinoma: An Uncommon Presentation.

Periampullary carcinoma is a broad term used to define the group of carcinomas arising from the head of the pancreas, the distal common bile duct, and the duodenum. It is clinically important to differentiate ampullary from periampullary carcinoma as this can affect resectability and prognosis. Atypical left-sided chest pain is an atypical presentation of periampullary duodenal adenocarcinoma. A 58-year-old man presented with a two-month duration of worsening intermittent, atypical, migratory left-sided chest pain. Imaging studies were unremarkable; however, endoscopic evaluation demonstrated a duodenal mass. While most periampullary carcinomas are generally curable with pancreaticoduodenectomy, if left untreated, these tumors are uniformly fatal.