Wilmington VA Medical Center

<bold>Rationale</bold>: Timely initiation of therapy reduces risks of acute COPD exacerbations (AECOPD). This study examined whether prompt initiation of single inhaler triple therapy (SITT) with budesonide/glycopyrronium/formoterol fumarate (BGF) following an AECOPD also lowers risk of future AECOPD and severe cardiopulmonary (CP) events. <bold>Methods:</bold> This retrospective study used US claims data from patients with COPD who were ≥40 years with no prior SITT and either: ≥1 severe or ≥2 moderate AECOPD, or ≥1 moderate AECOPD while on non-SITT treatment (earliest event = index date); all patients initiated BGF within 1-year following index. Outcomes were annualized rates per person/year of AECOPD and severe CP events. Severe CP events included mortality, severe AECOPD and hospitalizations for HF, AMI, and cardiac arrest. Descriptive results were presented and stratified by BGF initiation: prompt (≤30 days), delayed (31–180 days), and very delayed (181–365 days). <bold>Results:</bold> 17613 patients qualified: 2192 prompt, 7230 delayed, and 8191 very delayed. The rate per person/year (95% CI) of post-index AECOPD increased as the time to BGF initiation increased: prompt 1.35 (1.30–1.40); delayed 1.77 (1.74–1.79); and very delayed 1.98 (1.95–2.00). Total severe CP event rates were: prompt 0.34 (0.32–0.37); delayed 0.39 (0.38–0.40); and very delayed 0.38 (0.37–0.39). <bold>Conclusion</bold>: Promptly initiating BGF was associated with 24% and 32% fewer subsequent AECOPD and 12.3% and 9.3% fewer severe CP events compared with delayed and very delayed groups. Proactive disease management with BGF may be warranted to prevent future AECOPD and CP events among patients with COPD.

Selecting effective antidepressants for the treatment of major depressive disorder (MDD) is an imprecise practice, with remission rates of about 30% at the initial treatment. To determine whether pharmacogenomic testing affects antidepressant medication selection and whether such testing leads to better clinical outcomes. A pragmatic, randomized clinical trial that compared treatment guided by pharmacogenomic testing vs usual care. Participants included 676 clinicians and 1944 patients. Participants were enrolled from 22 Department of Veterans Affairs medical centers from July 2017 through February 2021, with follow-up ending November 2021. Eligible patients were those with MDD who were initiating or switching treatment with a single antidepressant. Exclusion criteria included an active substance use disorder, mania, psychosis, or concurrent treatment with a specified list of medications. Results from a commercial pharmacogenomic test were given to clinicians in the pharmacogenomic-guided group (n = 966). The comparison group received usual care and access to pharmacogenomic results after 24 weeks (n = 978). The co-primary outcomes were the proportion of prescriptions with a predicted drug-gene interaction written in the 30 days after randomization and remission of depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9) (remission was defined as PHQ-9 ≤ 5). Remission was analyzed as a repeated measure across 24 weeks by blinded raters. Among 1944 patients who were randomized (mean age, 48 years; 491 women [25%]), 1541 (79%) completed the 24-week assessment. The estimated risks for receiving an antidepressant with none, moderate, and substantial drug-gene interactions for the pharmacogenomic-guided group were 59.3%, 30.0%, and 10.7% compared with 25.7%, 54.6%, and 19.7% in the usual care group. The pharmacogenomic-guided group was more likely to receive a medication with a lower potential drug-gene interaction for no drug-gene vs moderate/substantial interaction (odds ratio [OR], 4.32 [95% CI, 3.47 to 5.39]; P < .001) and no/moderate vs substantial interaction (OR, 2.08 [95% CI, 1.52 to 2.84]; P = .005) (P < .001 for overall comparison). Remission rates over 24 weeks were higher among patients whose care was guided by pharmacogenomic testing than those in usual care (OR, 1.28 [95% CI, 1.05 to 1.57]; P = .02; risk difference, 2.8% [95% CI, 0.6% to 5.1%]) but were not significantly higher at week 24 when 130 patients in the pharmacogenomic-guided group and 126 patients in the usual care group were in remission (estimated risk difference, 1.5% [95% CI, -2.4% to 5.3%]; P = .45). Among patients with MDD, provision of pharmacogenomic testing for drug-gene interactions reduced prescription of medications with predicted drug-gene interactions compared with usual care. Provision of test results had small nonpersistent effects on symptom remission. ClinicalTrials.gov Identifier: NCT03170362.

Cutaneous protothecosis is a rare skin infection most commonly reported in immunocompromised individuals with recent exposure to contaminated soil or water. Cutaneous protothecosis has the potential to mimic many other skin diseases and lesions, including eczema; nonmelanoma skin cancer; or bacterial, viral, and fungal skin infections.

Le virus de l’hépatite C (HC) est un agent pathogène à transmission hématogène qui cause souvent une infection chronique du foie et expose les patients à la cirrhose, à la décompensation hépatique et au carcinome hépatocellulaire. Le traitement vise à faire disparaître le virus afin de réduire au minimum la morbidité et la mortalité causées par l’hépatite C. Comme traitement traditionnel, on utilise une combinaison interféron pégylé (IFN) et ribavirine qui cause souvent des effets secondaires à la fois systémiques et oculaires. Les hémorragies rétiniennes et les nodules cotonneux constituent les effets secondaires oculaires les plus courants, même si l’on a attribué, dans de rares cas, des événements indésirables ophtalmiques plus importants au traitement à l’IFN.&#x0D; Nous discutons ici d’un cas de neuropathie optique ischémique antérieure (NOIA) bilatérale qui s’est produit au cours d’un traitement à l’IFN et à la ribavirine contre l’hépatite C de génotype 1. Nous passons en revue la pathogénèse proposée des effets secondaires oculaires de ce traitement, ainsi que la pathogénèse et les facteurs de risque associés à la NOIA même. Enfin, nous formulerons des recommandations cliniques portant sur le dépistage d’autres problèmes en sus de la rétinopathie si un patient se présente avec des complications ophtalmiques.

Retinal macroaneurysms are an acquired vascular anomaly primarily associated with advancing age and hypertension. Although a rare pathology, it is not uncommon for a patient with a macroaneurysm to present to the primary care optometrist. Macroaneurysms have various presentations and they constitute one of the few clinical entities that can produce preretinal, intraretinal, subretinal or vitreal haemorrhage or any combination thereof. A review of the pathophysiology, differential diagnosis and newest treatments will be provided.A 68‐year‐old Caucasian male patient with a history of a previously treated retinal macroaneurysm presented to the eye clinic with acute‐onset visual loss in the same eye. The patient had a known diagnosis of hypertension and had been untreated by his primary care physician for one year. Dilated fundus examination revealed extensive multi‐layered haemorrhaging along with significant macular oedema. A choroidal neovascular membrane was ruled out with fluorescein angiography. The patient was treated with monthly bevacizumab injections over a period of three months. At six months optical coherence tomography confirmed the resolution of macular oedema and the patient achieved a marked improvement in his visual acuity.Retinal arterial macroaneurysm is one of the few clinical entities with the potential to produce any combination of preretinal, intraretinal, subretinal and/or vitreal haemorrhage. When the macula is threatened, treatment must be pursued. Although laser treatment has traditionally been used, anti‐vascular endothelial growth factor therapy has been used with promising visual outcomes.

Androgen suppression therapy (AST) was first described in 1941 as a treatment of prostate cancer (PCa) and remains the mainstay of therapy in patients with hormone-naïve metastatic disease. It also is used in locally advanced or recurrent disease and in combination with radiation therapy in patients with higher-risk features. Several approaches to AST have been developed as a result of increased understanding of the pathways controlling testosterone production. Increased recognition of the side effects has resulted in strategies to minimize complications associated with AST. Attempts to reduce AST adverse effects include intermittent hormonal therapy and methods to reduce amount of intracellular androgens without reducing the circulating testosterone levels.

Transseptal puncture is a standard means of catheter access to the left atrium via the venous system, but carries a risk of cardiac perforation. Stretching and increased force to traverse the septum are required with elastic, aneurysmal, or thickened interatrial tissue. We describe a technique that facilitates transseptal puncture by applying brief pulses of radiofrequency energy from a standard electrosurgical cautery generator through the needle tip.

Despite multiple inquiries, there are no available tests to definitively detect blunt myocardial injury. The evaluation of patients with chest wall injuries without other indications for intensive care unit (ICU) admission has ranged from a single emergency department electrocardiogram (ECG) to 72 hours of continuous electrocardiographic monitoring. Recently, signal-averaged ECG and serum cardiac troponin T have demonstrated clinical utility in the evaluation of ischemic heart disease. The purpose of this study is to determine the ability of these diagnostic tests to predict the occurrence of significant electrocardiographic rhythm disturbances for patients with chest wall injuries and no other indication for ICU admission. We prospectively evaluated 71 consecutive adult patients admitted to a regional Level I trauma center with chest wall injuries not requiring ICU admission. We obtained admission signal-averaged ECG, serum troponin T level, standard ECG, and creatine phosphokinase (CPK-MB) level. Patients received continuous electrocardiographic monitoring, follow-up 12-lead electrocardiography, and serial monitoring of troponin and CPK-MB. Echocardiography was performed for patients with abnormal CPK-MB levels. Electrocardiographic events were graded as normal, abnormal but clinically insignificant, or clinically significant. Multiple stepwise logistic regression analysis was used to evaluate predictors for the development of clinically significant electrocardiographic events. On admission, 17 of 71 patients (23.9%) had normal sinus rhythm; 13 (18.3%) had a clinically significant finding. For 50 patients, follow-up ECG was abnormal; for 26, the findings were clinically significant. Of 17 patients with normal initial ECGs, 7 (41%) developed a clinically significant abnormality. Six patients received intervention for ECG findings. Eleven of 71 patients (16%) had positive troponin T; 5 of 71 (7%) had positive CPK-MB; 15 of 71 (21%) had positive signal-averaged ECG; and 4 of 13 had positive echocardiograms. Initial electrocardiographic abnormalities and a troponin T level > 0.20 microg/L were the only variables found to predict clinically significant electrocardiographic events. Sensitivity and specificity of troponin T in predicting clinically significant abnormalities were 27 and 91%, respectively. 1. The best predictors for the development of significant electrocardiographic changes are an admission ECG abnormality and an elevated serum troponin T level. 2. Both tests have high specificity with low to moderate sensitivity. 3. Patients with normal ECGs may develop clinically significant events. 4. CPK-MB and echocardiograms continue to be poor predictors of significant electrocardiographic events.

From the Department of Surgery, Medical Center of Delaware, Wilmington, Delaware. Address for reprints: David D. Zabel, MD, Department of Surgery, Suite 128, 4745 Ogletown-Stanton Road, Newark, DE 19713.