Citations

SummaryBackgroundThere are limited data to inform positioning of agents for treating moderate‐severe ulcerative colitis (UC).AimTo assess comparative efficacy and safety of different therapies as first‐line (biologic‐naïve) and second‐line (prior exposure to anti‐tumour necrosis factor(TNF)‐α) agents for moderate‐severe UC, through a systematic review and network meta‐analysis, and appraise quality of evidence (QoE) using grading of recommendations, assessment, development and evaluation (GRADE) approach.MethodsWe identified randomised controlled trials (RCTs) in adults with moderate‐severe UC treated with anti‐TNF agents, anti‐integrin agents and janus kinase (JAK) inhibitors, as first‐line or second‐line agents, and compared with placebo or another active agent. Efficacy outcomes were induction/maintenance of remission and mucosal healing; and safety outcomes were serious adverse events and infections. Network meta‐analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities.ResultsIn biologic‐naïve patients (12 trials, no head‐to‐head comparisons), infliximab and vedolizumab were ranked highest for induction of clinical remission (infliximab: odds ratio [OR], 4.10 [95% confidence intervals [CI], 2.58‐6.52]; SUCRA,0.85; vedolizumab:SUCRA,0.82) and mucosal healing (infliximab:SUCRA,0.91; vedolizumab:SUCRA,0.81) (moderate QoE). In patients with prior anti‐TNF exposure (4 trials, no head‐to‐head comparisons), tofacitinib was ranked highest for induction of clinical remission (OR, 11.88 [2.32‐60.89]; SUCRA, 0.96) and mucosal healing (moderate QoE). Differences in trial design limited comparability of trials of maintenance therapy for efficacy. Vedolizumab was ranked safest in terms of serious adverse events (SUCRA, 0.91), and infection (SUCRA, 0.75) in maintenance trials.ConclusionsInfliximab and vedolizumab are ranked highest as first‐line agents, and tofacitinib is ranked highest as second‐line agent, for induction of remission and mucosal healing in patients with moderate‐severe UC, based on indirect comparisons. Head‐to‐head trials are warranted to inform clinical decision‐making with greater confidence.

AbstractBackgroundThe implications of early readmission on long‐term mortality after transient ischemic attack (TIA) are not known. We aimed at examining the effect of 180‐day readmission on subsequent long‐term mortality after index hospitalization for TIA.MethodsA retrospective study of patients hospitalized for first‐ever TIA at Mayo Clinic from 2000 through 2017. Patients readmitted within 180 days postdischarge were compared with those not readmitted in long‐term risk of death.ResultsOf 251 TIA patients aged 73 ± 15 years with 1509 person‐years of follow‐up, 65 (26%) were readmitted within 180 days of discharge and 125 died during a median follow‐up of 5.7 years. The mortality was 10 vs. 7 deaths per 100 person‐years in patients who were readmitted compared to those who were not readmitted with hazard ratio (HR) 1.73 (95% confidence interval [CI] 1.13–2.66). Other competing predictors of mortality were age ≥65 years (HR 5.70, 95% CI 2.72–11.96), cancer (HR 1.65, 95% CI 1.03–3.38), chronic obstructive pulmonary disease (HR 1.90, 95% CI 1.07–3.38), heart failure (HR 3.03, 95% CI 1.82–5.06), dementia (HR 5.87, 95% CI 3.27–10.52), creatinine ≥1.4 mg/dl (HR 1.89, 95% CI 1.17–3.06), and hemoglobin level <10 g/dl (HR 2.80, 95% CI 1.20–6.66).ConclusionsHospital readmission within 180 days of discharge from index TIA was associated with increased risk of death several years after initial readmission. Older age and several comorbidities identified during index hospitalization also confer increased risk for long‐term mortality.

Background and Purpose— There is currently controversy on the ideal anesthesia strategy during mechanical thrombectomy for acute ischemic stroke. We performed a systematic review and meta-analysis of studies comparing clinical and angiographic outcomes of patients undergoing general anesthesia (GA group) and those receiving either local anesthesia or conscious sedation (non-GA group). Methods— A literature search on anesthesia and endovascular treatment of acute ischemic stroke was performed. Using random-effects meta-analysis, we evaluated the following outcomes: recanalization rate, good functional outcome at 90 days (modified Rankin Score≤2), symptomatic intracranial hemorrhage, death, vascular complications, respiratory complications, procedure time, and time to groin puncture. Results— Twenty-two studies (3 randomized controlled trials and 19 observational studies), including 4716 patients (1819 GA and 2897 non-GA) were included. In the nonadjusted analysis, patients in the GA group had higher odds of death (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.66–2.45) and respiratory complications (OR, 1.70; 95% CI, 1.22–2.37) and lower odds of good functional outcome (OR, 0.58; 95% CI, 0.48–0.64) compared with the non-GA group. There was no difference in procedure time between the 2 primary comparison groups. When adjusting for baseline National Institutes of Health Stroke Scale, GA was still associated with lower odds of good functional outcome (OR, 0.59; 95% CI, 0.29–0.94). When considering studies performed in the stent-retriever/aspiration era, there was no significant difference in good neurological outcome rates (OR, 0.84; 95% CI, 0.67–1.06). Conclusions— Acute ischemic stroke patients undergoing intra-arterial therapy may have worse outcomes when treated with GA as compared with conscious sedation/local anesthesia. However, major limitations of current evidence (ie, retrospective studies and selection bias) indicate a need for adequately powered, multicenter randomized controlled trials to answer this question.

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)

Background Hospital discharge summaries enable communication between inpatient and outpatient physicians. Despite existing guidelines for discharge summaries, they are frequently suboptimal. Objective The aim of this study was to assess physicians’ perspectives about discharge summaries and the differences between summaries’ authors (hospitalists) and readers (primary care physicians [PCPs]). Methods A national survey of 1600 U.S. physicians was undertaken. Primary measures included physicians’ preferences in discharge summary standardization, content, format, and audience. Results A total of 815 physicians responded (response rate = 51%). Eighty-nine percent agreed that discharge summaries “should have a standardized format.” Most agreed that summaries should “document everything that was done, found, and recommended in the hospital” (64%) yet “only include details that are highly pertinent to the hospitalization” (66%). Although 74% perceived patients as an important audience of discharge summaries, only 43% agreed that summaries “should be written in language that patients…can easily understand,” and 68% agreed that it “should be written solely for provider-to-provider communication.” Compared with hospitalists, PCPs preferred comprehensive summaries (68% versus 59%, P = 0.002). More PCPs agreed that separate summaries should be created for patients and for provider-to-provider communication than hospitalists (60% versus 47%, P < 0.001). Compared with PCPs, more hospitalists believe that “hospitalists are too busy to prepare a high-quality discharge summary” (44% versus 23%, P < 0.001) and “PCPs have insufficient time to read an entire discharge summary” (60% versus 38%, P < 0.001). Conclusions Physicians believe that discharge summaries should have a standardized format but do not agree on how comprehensive or in what format they should be. Efforts are necessary to build consensus toward the ideal discharge summary.

SummaryBackgroundHepatitis E virus (HEV) infection appears to be more common than previously thought. HEV seroprevalence in patients on maintenance haemodialysis (HD) is unclear with a range from 0% to 44%. In addition, risk factors of transmission of HEV in patients on haemodialysis are unknown.AimTo perform a systematic review and meta‐analysis of HEV seroprevalence in HD patients compared with controls.MethodsA systematic search of several databases identified all observational studies with comparative arms. Two reviewers extracted data and assessed the methodological quality. A random‐effects model was used for pooled odds ratio (OR) and 95% confidence interval (CI) of positive anti‐HEV IgG in both groups. Heterogeneity and publication bias were assessed with appropriate tests.ResultsWe identified 31 studies from 17 countries between 1994 and 2016. Sixteen studies were judged to have adequate quality and 15 to have moderate limitations. HEV infection was more prevalent in patients on haemodialysis compared with controls (OR 2.47, 95% CI 1.79‐3.40, I2 = 75.2%, P < .01). We conducted several subgroup analyses without difference in results. Egger regression test did not suggest publication bias (P = .83). Specific risk factors of HEV transmission in patients on haemodialysis were not clearly identified.ConclusionsHepatitis E virus infection is more prevalent in patients on haemodialysis compared with non‐haemodialysis control groups. Further studies are needed to determine risk factors of acquisition, impact on health, and risk for chronic HEV especially among those patients going to receive organ transplantation.

Multiphasic computed tomography (CT) and magnetic resonance imaging (MRI) are both used for noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. To determine if there is a relative diagnostic benefit of one over the other, we synthesized evidence regarding the relative performance of CT, extracellular contrast–enhanced MRI, and gadoxetate‐enhanced MRI for diagnosis of HCC in patients with cirrhosis. We also assessed whether liver biopsy versus follow‐up with the same versus alternative imaging is best for CT‐indeterminate or MRI‐indeterminate liver nodules in patients with cirrhosis. We searched multiple databases from inception to April 27, 2016, for studies comparing CT with extracellular contrast–enhanced MRI or gadoxetate‐enhanced MRI in adults with cirrhosis and suspected HCC. Two reviewers independently selected studies and extracted data. Of 33 included studies, 19 were comprehensive, while 14 reported sensitivity only. For all tumor sizes, the 19 comprehensive comparisons showed significantly higher sensitivity (0.82 versus 0.66) and lower negative likelihood ratio (0.20 versus 0.37) for MRI over CT. The specificities of MRI versus CT (0.91 versus 0.92) and the positive likelihood ratios (8.8 versus 8.1) were not different. All three modalities performed better for HCCs ≥2 cm. Performance was poor for HCCs <1 cm. No studies examined whether adults with cirrhosis and an indeterminate nodule are best evaluated using biopsy, repeated imaging, or alternative imaging. Concerns about publication bias, inconsistent study results, increased risk of bias, and clinical factors precluded support for exclusive use of either gadoxetate‐enhanced or extracellular contrast–enhanced MRI over CT.Conclusion:CT, extracellular contrast–enhanced MRI, or gadoxetate‐enhanced MRI could not be definitively preferred for HCC diagnosis in patients with cirrhosis; in patients with cirrhosis and an indeterminate mass, there were insufficient data comparing biopsy to repeat cross‐sectional imaging or alternative imaging. (Hepatology2018;67:401‐421).

Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are often treated while on the waiting list with locoregional therapy (LRT), which is aimed at either preventing progression of HCC or reducing the measurable disease burden of HCC in order to receive increased allocation priority. We aimed to synthesize evidence regarding the effectiveness of LRT in the management of patients with HCC who were on the LT waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down‐staging therapies before LT. Therapies included transcatheter arterial chemoembolization, transarterial radioembolization, ablation, and radiotherapy. We included both comparative and noncomparative studies. There were no randomized controlled trials identified. For adults with T1 HCC and waiting for LT, there were only two nonrandomized comparative studies, both with a high risk of bias, which reported the outcome of interest. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow‐up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95% confidence interval [CI], 0.06‐1.85; I 2 = 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060‐2.370; I 2 = 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studies which reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any down‐staging therapy versus no downstaging, and this showed a significant increase in 1‐year (two studies, RR, 1.11; 95% CI, 1.01‐1.23) and 5‐year (1 study, RR, 1.17; 95% CI, 1.03‐1.32) post‐LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision. Conclusion: In patients with HCC listed for LT, the use of LRT is associated with a nonsignificant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence. (H epatology 2018;67:381‐400).