The Management of Major Depressive Disorder: Synopsis of the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

DESCRIPTION: In February 2022, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of major depressive disorder (MDD). This synopsis summarizes key recommendations. METHODS: Senior leaders within the VA and the DoD assembled a team to update the 2016 CPG for the management of MDD that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 36 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Select recommendations that were identified by the authors to represent key changes from the prior CPG are presented in this synopsis. RECOMMENDATIONS: The scope of the CPG is diverse; however, this synopsis focuses on key recommendations that the authors identified as important new evidence and changes to prior recommendations on pharmacologic management, pharmacogenomics, psychotherapy, complementary and alternative therapies, and the use of telemedicine.

Substandard and Falsified Medications: A Barrier to Global Health Equity Exemplified in Ecuador.

Medicines have been developed and have become globalized at a pace faster than traditional medical education can keep up. Physicians, pharmacists, nurses, and advanced practice providers learn the names and functions of these medications, but not how they are made and how they get to the bedside. The often economically driven intricacies behind these processes have a dramatic effect on patient care and outcomes. A staggering proportion of medications worldwide are reported to be substandard or falsified. This article explores one country's story of how medication gets to the bedside, describes how this process can go wrong, and outlines what providers can do to work toward the goal of equitable access to quality medications for all.

The management and rehabilitation of post-acute mild traumatic brain injury.

DESCRIPTION: In June 2021, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the management and rehabilitation care for those who have symptoms in the post-acute period following mild traumatic brain injury (mTBI). This synopsis describes some of the clinically important recommendations. METHODS: In January 2020, VA and DoD leaders assembled a joint VA/DoD guideline development team of multidisciplinary clinical stakeholders that developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and refined 19 recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The process closely conformed to the National Academy of Medicine's tenets for trustworthy clinical practice guidelines. RECOMMENDATIONS: This synopsis describes clinically important recommendations for the management and rehabilitation of mTBI. Outpatient primary care providers are the target audience for this synopsis and guideline. The current recommendations are an update from the 2016 VA/DoD Clinical Practice Guidelines for the Management of Concussion-Mild Traumatic Brain Injury.

Vascular Malformation and CAP Polyposis: A New Insight into Pathophysiology or Fortuitous Association?

INTRODUCTION: CAP polyposis is a benign colorectal process presenting with multiple colorectal polyps with a "CAP" of inflammatory granulation tissue whose etiology has remained largely unknown. CASE: A 24-year-old male presented with a long-standing history of repeated multiple sessile colonic polyps over a period of 17 years. RESULTS: The numerous polyps showed consistent histologic features of superficial erosion with a surface "CAP" of granulation tissue with minimal submucosa to evaluate over this period. A left hemicolectomy disclosed an extensive vascular malformation. CONCLUSION: The underlying vascular malformation may have an etiologic correlation to the overlying CAP polyps in this patient. Future cases may benefit from an evaluation of the underlying submucosa for the presence of possible vascular malformation likely to be missed on superficial polypectomy.

Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia.

BACKGROUND: Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking. METHODS: We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target. The primary safety end point was treatment-related serious adverse events in the first 90 days. The primary efficacy end point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment). Health-related quality of life was assessed using the Short Form-36 questionnaire. RESULTS: Nineteen patients were enrolled (17 for VT, 2 for PVC cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4-32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related serious adverse event. The median number of VT episodes was reduced from 119 (range, 4-292) to 3 (range, 0-31; P<0.001). Reduction was observed for both implantable cardioverter defibrillator shocks and antitachycardia pacing. VT episodes or PVC burden were reduced in 17/18 evaluable patients (94%). The frequency of VT episodes or PVC burden was reduced by 75% in 89% of patients. Overall survival was 89% at 6 months and 72% at 12 months. Use of dual antiarrhythmic medications decreased from 59% to 12% ( P=0.008). Quality of life improved in 5 of 9 Short Form-36 domains at 6 months. CONCLUSIONS: Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02919618.

Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia.

BACKGROUND: Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter-free, electrophysiology-guided, noninvasive cardiac radioablation for ventricular tachycardia. METHODS: We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter-defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging. RESULTS: From April through November 2015, five patients with high-risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6-week postablation "blanking period" (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6-week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient-months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year. CONCLUSIONS: In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology-guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes-Jewish Hospital Foundation and others.).

Delayed Metastasis of Clear Cell Sarcoma of Kidney to Bladder After 7 Disease-Free Years.

INTRODUCTION: Clear cell sarcoma of the kidney (CCSK) is childhood neoplasm with its own distinctive pattern of metastasis and may appear after a disease free interval of 5 years or more. MATERIALS AND METHODS: Histopathology and immunohistochemistry were available from the radical nephrectomy and the later partial cystectomy, which was performed after a seven disease-free interval. RESULTS: The pathologic features of the primary tumor were those of a classic CCSK with a monotypic pattern of uniform rounded to ovoid tumor cells with a background network of delicate blood vessels. By contrast, the bladder recurrence had a myxoid hypocellular appearance (one of the known variant patterns of CCSK). Both tumors displayed immunopositivity for Cyclin-D1 and CD117 with a less intense reaction in the bladder metastasis. CONCLUSIONS: This case demonstrates that CCSK has the potential to metastasize after a prolonged disease-free interval and may have deceptively bland histopathologic features.

Clinical implications for patients treated inappropriately for community-acquired pneumonia in the emergency department.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the most common infections presenting to the emergency department (ED). Increasingly, antibiotic resistant bacteria have been identified as causative pathogens in patients treated for CAP, especially in patients with healthcare exposure risk factors. METHODS: We retrospectively identified adult subjects treated for CAP in the ED requiring hospital admission (January 2003-December 2011). Inappropriate antibiotic treatment, defined as an antibiotic regimen that lacked in vitro activity against the isolated pathogen, served as the primary end point. Information regarding demographics, severity of illness, comorbidities, and antibiotic treatment was recorded. Logistic regression was used to determine factors independently associated with inappropriate treatment. RESULTS: The initial cohort included 259 patients, 72 (27.8%) receiving inappropriate antibiotic treatment. There was no difference in hospital mortality between patients receiving inappropriate and appropriate treatment (8.3% vs. 7.0%; p = 0.702). Hospital length of stay (10.3 ± 12.0 days vs. 7.0 ± 8.9 days; p = 0.017) and 30-day readmission (23.6% vs. 12.3%; p = 0.024) were greater among patients receiving inappropriate treatment. Three variables were independently associated with inappropriate treatment: admission from long-term care (AOR, 9.05; 95% CI, 3.93-20.84), antibiotic exposure in the previous 30 days (AOR, 1.85; 95% CI, 1.35-2.52), and chronic obstructive pulmonary disease (AOR, 2.05; 95% CI, 1.52-2.78). CONCLUSION: Inappropriate antibiotic treatment of presumed CAP in the ED negatively impacts patient outcome and readmission rate. Knowledge of risk factors associated with inappropriate antibiotic treatment of presumed CAP could advance the management of patients with pneumonia presenting to the ED and potentially improve patient outcomes.

Subsequent ischemic stroke and tobacco smoking: A secondary analysis of the POINT trial.

Background: The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the effect of clopidogrel-based DAPT on subsequent stroke risk. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively. Results: Data from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97-1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56-0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37-1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40-7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08-6.21), p = 0.032), p for interaction = 0.613. Conclusions: In this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers.