Background Preoperative physical fitness is predictive of postoperative outcome. Patients with lesser aerobic capacity are at greater risk of postoperative complications, longer hospital stays, and ...mortality. Prehabilitation may improve physical fitness, but it is unknown whether enhanced fitness translates to an improvement in postoperative outcome. Methods This systematic review and meta-analysis aimed to assess the ability of prehabilitation to influence postoperative outcome after intra-abdominal operations. Randomized controlled trials with at least 1 group undergoing a preoperative exercise intervention/prehabilitation were included. The following databases were searched: AMED, CINAHL, EMBASE, PubMed/Medline, and The Cochrane Library. Data extracted from 9 full-articles included author(s), population demographics, type of operation, postoperative measures of outcome, and type of treatment of the prehabilitation and control groups. Methodologic quality was assessed using GRADEpro, and the Cochrane risk of bias tool was used to measure study bias. Results Prehabilitation consisting of inspiratory muscle training, aerobic exercise, and/or resistance training can decrease all types of postoperative complications after intra-abdominal operations (odds ratio: 0.59, 95% confidence interval: 0.38–0.91, P = .03). It is unclear from our meta-analysis whether prehabilitation can decrease postoperative length of stay, because the number of studies that examined length of stay was small ( n = 4). No postoperative mortality was reported in any study, and conclusions could not be drawn on the ability of exercise to influence operative mortality. The methodologic quality of studies was, however, “very low.” Conclusion Prehabilitation appears to be beneficial in decreasing the incidence of postoperative complications; however, more high-quality studies are needed to validate its use in the preoperative setting.
Abstract Background Pulmonary hypertension (PH) is a common and morbid complication of left heart disease with 2 subtypes: isolated post-capillary pulmonary hypertension (Ipc-PH) and combined ...post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Little is known about the clinical or physiological characteristics that distinguish these 2 subphenotypes or if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH). Objectives The goal of this study was to test the hypothesis that the hemodynamic and genetic profile of Cpc-PH would more closely resemble PAH than Ipc-PH. Methods Vanderbilt University’s electronic medical record linked to a DNA biorepository was used to extract demographic characteristics, clinical data, invasive hemodynamic data, echocardiography, and vital status for all patients referred for right heart catheterization between 1998 and 2014. Shared genetic variants between PAH and Cpc-PH compared with Ipc-PH were identified by using pre-existing single-nucleotide polymorphism data. Results A total of 2,817 patients with PH (13% Cpc-PH, 52% Ipc-PH, and 20% PAH) were identified. Patients with Cpc-PH were on average 6 years younger, with more severe pulmonary vascular disease than patients with Ipc-PH, despite similar comorbidities and prevalence, severity, and chronicity of left heart disease. After adjusting for relevant covariates, the risk of death was similar between the Cpc-PH and Ipc-PH groups (hazard ratio: 1.14; 95% confidence interval: 0.96 to 1.35; p = 0.15) when defined according to diastolic pressure gradient. We identified 75 shared exonic single-nucleotide polymorphisms between Cpc-PH and PAH enriched in pathways involving cell structure, extracellular matrix, and immune function. These genes are expressed, on average, 32% higher in lungs relative to other tissues. Conclusions Patients with Cpc-PH develop pulmonary vascular disease similar to patients with PAH, despite younger age and similar prevalence of obesity, diabetes mellitus, and left heart disease compared with patients with Ipc-PH. An exploratory genetic analysis in Cpc-PH identified genes and biological pathways in the lung known to contribute to PAH pathophysiology, suggesting that Cpc-PH may be a distinct and highly morbid PH subphenotype.
Esophageal perforation in achalasia is rare. The risk would mainly follow pneumatic dilatation, and spontaneous perforation has not been described. We report a case of spontaneous rupture of the ...midesophagus in a 56-year-old woman with treated achalasia in whom the perforation occurred during a meal and was not preceded by emesis. A gastrografin swallow confirmed extravasation of contrast medium from the esophagus, and endoscopy revealed significant esophageal food stasis, consistent with achalasia, with a large tear in the midesophagus and gross mediastinal contamination. She subsequently underwent a three-stage esophagectomy with an uneventful recovery.
Since its original development in Oregon in 1993, Physician Orders for Life-Sustaining Treatment (POLST) is quickly growing in popularity and prevalence as a method of communicating the end-of-life ...care preferences for the seriously ill and frail nationwide. Early evidence has suggested significant advantages over advance directives and do-not-resuscitate/do-not-intubate documents both in accuracy and penetration within relevant populations. POLST also may contribute to the quality of end-of-life care administered. Although it was designed to be as clear as possible, unexpected challenges in the interpretation and use of POLST in the emergency department do exist. In this article, we will discuss the history, ethical considerations, legal issues, and emerging trends in the use of POLST documents as they apply to emergency medicine.
Summary Background In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAFV600 mutation-positive melanoma. ...We present an extended follow-up analysis of the total population and in the BRAFV600E and BRAFV600K mutation subgroups. Methods Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAFV600 mutations were eligible. Patients also had to have a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate haematological, hepatic, and renal function. Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m2 of body surface area intravenously every 3 weeks). Coprimary endpoints were overall survival and progression-free survival, analysed in the intention-to-treat population (n=675), with data censored at crossover. A sensitivity analysis was done. This trial is registered with ClinicalTrials.gov , NCT01006980. Findings 675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4, 2010, and Dec 16, 2010. 337 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine. Median follow-up was 12·5 months (IQR 7·7–16·0) on vemurafenib and 9·5 months (3·1–14·7) on dacarbazine. 83 (25%) of the 338 patients initially randomly assigned to dacarbazine crossed over from dacarbazine to vemurafenib. Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group (13·6 months 95% CI 12·0–15·2 vs 9·7 months 7·9–12·8; hazard ratio HR 0·70 95% CI 0·57–0·87; p=0·0008), as was median progression-free survival (6·9 months 95% CI 6·1–7·0 vs 1·6 months 1·6–2·1; HR 0·38 95% CI 0·32–0·46; p<0·0001). For the 598 (91%) patients with BRAFV600E disease, median overall survival in the vemurafenib group was 13·3 months (95% CI 11·9–14·9) compared with 10·0 months (8·0–14·0) in the dacarbazine group (HR 0·75 95% CI 0·60–0·93; p=0·0085); median progression-free survival was 6·9 months (95% CI 6·2–7·0) and 1·6 months (1·6–2·1), respectively (HR 0·39 95% CI 0·33–0·47; p<0·0001). For the 57 (9%) patients with BRAFV600K disease, median overall survival in the vemurafenib group was 14·5 months (95% CI 11·2–not estimable) compared with 7·6 months (6·1–16·6) in the dacarbazine group (HR 0·43 95% CI 0·21–0·90; p=0·024); median progression-free survival was 5·9 months (95% CI 4·4–9·0) and 1·7 months (1·4–2·9), respectively (HR 0·30 95% CI 0·16–0·56; p<0·0001). The most frequent grade 3–4 events were cutaneous squamous-cell carcinoma (65 19% of 337 patients) and keratoacanthomas (34 10%), rash (30 9%), and abnormal liver function tests (38 11%) in the vemurafenib group and neutropenia (26 9% of 287 patients) in the dacarbazine group. Eight (2%) patients in the vemurafenib group and seven (2%) in the dacarbazine group had grade 5 events. Interpretation Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAFV600E mutation and in patients with the less common BRAFV600K mutation. Funding F Hoffmann-La Roche-Genentech.
Prescription drug monitoring programs are statewide databases available to clinicians to track prescriptions of controlled medications. These programs may provide valuable information to assess the ...history and use of controlled substances and contribute to clinical decisionmaking in the emergency department (ED). The widespread availability of the programs raises important ethical issues about beneficence, nonmaleficence, respect for persons, justice, confidentiality, veracity, and physician autonomy. In this article, we review the ethical issues surrounding prescription drug monitoring programs and how those issues might be addressed to ensure the proper application of this tool in the ED. Clinical decisionmaking in regard to the appropriate use of opioids and other controlled substances is complex and should take into account all relevant clinical factors, including age, sex, clinical condition, medical history, medication history and potential drug-drug interactions, history of addiction or diversion, and disease state.
Summary Background Previously, a study of ours showed that the combination of dabrafenib and trametinib improves progression-free survival compared with dabrafenib and placebo in patients with BRAF ...Val600Lys/Glu mutation-positive metastatic melanoma. The study was continued to assess the secondary endpoint of overall survival, which we report in this Article. Methods We did this double-blind phase 3 study at 113 sites in 14 countries. We enrolled previously untreated patients with BRAF Val600Glu or Val600Lys mutation-positive unresectable stage IIIC or stage IV melanoma. Participants were computer-randomised (1:1) to receive a combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily), or dabrafenib and placebo. The primary endpoint was progression-free survival and overall survival was a secondary endpoint. This study is registered with ClinicalTrials.gov , number NCT01584648. Findings Between May 4, 2012, and Nov 30, 2012, we screened 947 patients for eligibility, of whom 423 were randomly assigned to receive dabrafenib and trametinib (n=211) or dabrafenib only (n=212). The final data cutoff was Jan 12, 2015, at which time 222 patients had died. Median overall survival was 25·1 months (95% CI 19·2–not reached) in the dabrafenib and trametinib group versus 18·7 months (15·2–23·7) in the dabrafenib only group (hazard ratio HR 0·71, 95% CI 0·55–0·92; p=0·0107). Overall survival was 74% at 1 year and 51% at 2 years in the dabrafenib and trametinib group versus 68% and 42%, respectively, in the dabrafenib only group. Based on 301 events, median progression-free survival was 11·0 months (95% CI 8·0–13·9) in the dabrafenib and trametinib group and 8·8 months (5·9–9·3) in the dabrafenib only group (HR 0·67, 95% CI 0·53–0·84; p=0·0004; unadjusted for multiple testing). Treatment-related adverse events occurred in 181 (87%) of 209 patients in the dabrafenib and trametinib group and 189 (90%) of 211 patients in the dabrafenib only group; the most common was pyrexia (108 patients, 52%) in the dabrafenib and trametinib group, and hyperkeratosis (70 patients, 33%) in the dabrafenib only group. Grade 3 or 4 adverse events occurred in 67 (32%) patients in the dabrafenib and trametinib group and 66 (31%) patients in the dabrafenib only group. Interpretation The improvement in overall survival establishes the combination of dabrafenib and trametinib as the standard targeted treatment for BRAF Val600 mutation-positive melanoma. Studies assessing dabrafenib and trametinib in combination with immunotherapies are ongoing. Funding GlaxoSmithKline.
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