Prokop, Larry J.

Background. This systematic review was commissioned to identify new variables associated with transplant outcomes that are not currently collected by the Organ Procurement and Transplantation Network (OPTN). Methods. We identified 81 unique studies including 1 193 410 patients with median follow-up of 36 months posttransplant, reporting 108 unique risk factors. Results. Most risk factors (104) were recipient related; few (4) were donor related. Most risk factors were judged to be practical and feasible to routinely collect. Relative association measures were small to moderate for most risk factors (ranging between 1.0 and 2.0). The strongest relative association measure for a heart transplant outcome with a risk factor was 8.6 (recipient with the previous Fontan operation), for a kidney transplant 2.8 (sickle cell nephropathy as primary cause of end-stage renal disease), for a liver transplant 14.3 (recipient serum ferritin >500 µg/L), and for a lung transplant 6.3 (Burkholderia cepacia complex infection for 1 y or less). OPTN may consider some of these 108 variables for future collection to enhance transplant research and clinical care. Conclusions. Evidence-based approaches can be used to determine variables collected in databases and registries. Several candidate variables have been identified for OPTN.

Purpose The authors sought to summarize quantitative and qualitative research addressing electronic knowledge resources and point-of-care learning in a scoping review. Method The authors searched MEDLINE, Embase, PsycINFO, and the Cochrane Database for studies addressing electronic knowledge resources and point-of-care learning. They iteratively revised inclusion criteria and operational definitions of study features and research themes of interest. Two reviewers independently performed each phase of study selection and data extraction. Results Of 10,811 studies identified, 305 were included and reviewed. Most studies (225; 74%) included physicians or medical students. The most frequently mentioned electronic resources were UpToDate (88; 29%), Micromedex (59; 19%), Epocrates (50; 16%), WebMD (46; 15%), MD Consult (32; 10%), and LexiComp (31; 10%). Eight studies (3%) evaluated electronic resources or point-of-care learning using outcomes of patient effects, and 36 studies (12%) reported objectively measured clinician behaviors. Twenty-five studies (8%) examined the clinical or educational impact of electronic knowledge resource use on patient care or clinician knowledge, 124 (41%) compared use rates of various knowledge resources, 69 (23%) examined the quality of knowledge resource content, and 115 (38%) explored the process of point-of-care learning. Two conceptual clarifications were identified, distinguishing the impact on clinical or educational outcomes versus the impact on test setting decision support, and the quality of information content versus the correctness of information obtained by a clinician–user. Conclusions Research on electronic knowledge resources is dominated by studies involving physicians and evaluating use rates. Studies involving nonphysician users, and evaluating resource impact and implementation, are needed.

Abstract Background Females with congenital adrenal hyperplasia (CAH) and atypical genitalia often undergo complex surgeries; however, their outcomes remain largely uncertain. Methods We searched several databases through 8 March 2016 for studies evaluating genital reconstructive surgery in females with CAH. Reviewers working independently and in duplicate selected and appraised the studies. Results We included 29 observational studies (1178 patients, mean age at surgery, 2.7 ± 4.7 years; mostly classic CAH). After an average follow-up of 10.3 years, most patients who had undergone surgery had a female gender identity (88.7%) and were heterosexual (76.2%). Females who underwent surgery reported a sexual function score of 25.13 using the Female Sexual Function Index (maximum score, 36). Many patients continued to complain of substantial impairment of sensitivity in the clitoris, vaginal penetration difficulties, and low intercourse frequency. Most patients were sexually active, although only 48% reported comfortable intercourse. Most patients (79.4%) and treating health care professionals (71.8%) were satisfied with the surgical outcomes. Vaginal stenosis was common (27%), and other surgical complications, such as fistulas, urinary incontinence, and urinary tract infections, were less common. Data on quality of life were sparse and inconclusive. Conclusion The long-term follow-up of females with CAH who had undergone urogenital reconstructive surgery shows variable sexual function. Most patients were sexually active and satisfied with the surgical outcomes; however, some patients still complained of impairment in sexual experience and satisfaction. The certainty in the available evidence is very low.

Summary Objective Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined. Design We performed a systematic review and meta‐analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters. Methods We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta‐analysis and plotted over time. Results We included 71 studies reporting peri‐operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri‐operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response. Conclusions The peri‐operative cortisol stress response is dynamic and influenced by patient‐specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.

AbstractBackground & AimsAcute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4.MethodsTwo reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus‐RNA positive vs negative, and to discern important mortality risk factors.ResultsWe identified 65 patients, with median age 58 years (range: 3‐79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus‐RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA.ConclusionAcute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle‐aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis.

Background There is no consensus on the most effective and best tolerated first‐line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and meta‐analysis was to compare the efficacy, safety, and fetal–maternal tolerance of first‐line monotherapies for fetal supraventricular tachycardia and atrial flutter. Methods and Results A comprehensive search of several databases was conducted through January 2017. Only studies that made a direct comparison between first‐line treatments of fetal tachyarrhythmia were included. Outcomes of interest were termination of fetal tachyarrhythmia, fetal demise, and maternal complications. Ten studies met inclusion criteria, with 537 patients. Overall, 291 patients were treated with digoxin, 137 with flecainide, 102 with sotalol, and 7 with amiodarone. Digoxin achieved a lower rate of supraventricular tachycardia termination compared with flecainide (odds ratio [ OR ]: 0.773; 95% confidence interval [ CI ], 0.605–0.987; I 2 =34%). In fetuses with hydrops fetalis, digoxin had lower rates of tachycardia termination compared with flecainide ( OR : 0.412; 95% CI , 0.268–0.632; I 2 =0%). There was no significant difference in the incidence of maternal side effects between digoxin and flecainide groups ( OR : 1.134; 95% CI , 0.129–9.935; I 2 =80.79%). The incidence of maternal side effects was higher in patients treated with digoxin compared with sotalol ( OR : 3.148; 95% CI , 1.468–6.751; I 2 =0%). There was no difference in fetal demise between flecainide and digoxin ( OR : 0.767; 95% CI , 0.140–4.197; I 2 =44%). Conclusions Flecainide may be more effective treatment than digoxin as a first‐line treatment for fetal supraventricular tachycardia.

Hepatocellular carcinoma (HCC) is a complex disease most commonly arising in the background of chronic liver disease. In the past two decades, there has been a significant increase in our understanding of both the clinical and molecular heterogeneity of HCC. There has been a robust increase in clinical trial activity in patients with poor prognostic factors, such as macrovascular invasion and extrahepatic spread (EHS). We aimed to synthesize the evidence for the treatment of patients with advanced HCC based on these baseline characteristics, including patients with both Child‐Pugh (CP) scores of A and B. A comprehensive search of several databases from each database inception to February 15, 2016 any language was conducted. We included 14 studies (three randomized controlled studies [RCTs] and 11 observational studies). We included studies that compared sorafenib, transarterial bland embolization/transarterial chemoembolization, yttrium‐90/radiation therapy, ablation (or combination), and no therapy. Two RCTs comparing sorafenib to best supportive care demonstrated a consistent improvement in overall survival (OS) for patients with advanced HCC and metastatic vascular invasion (MVI) and/or EHS and CP A liver disease (hazard ratio, 0.66 [95% confidence interval, 0.51‐0.87]; I 2 = 0%). Several observational studies evaluated locoregional therapies alone or in combination with other treatments and were limited by very‐low‐quality of evidence. This was true for both patients with EHS and MVI. Conclusion : In patients with advanced HCC and CP A liver function, sorafenib is the only treatment that has been shown to improve OS in randomized studies. High‐quality data supporting the use of other treatment modalities in this setting, or in the setting of patients with less compensated (CP B) liver disease, are lacking. (H epatology 2018;67:422‐435)