Serious Adverse Events In Patients Research Articles

Heterogeneity of treatment effect of prophylactic pantoprazole in adult ICU patients: a post hoc analysis of the SUP-ICU trial.

The Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial compared prophylactic pantoprazole with placebo in 3291 adult ICU patients at risk of clinically important gastrointestinal bleeding (CIB). As a predefined subgroup analysis suggested increased 90-day mortality with pantoprazole in the most severely ill patients, we aimed to further explore whether heterogenous treatment effects (HTE) were present. We assessed HTE in subgroups defined according to illness severity by SAPS II quintiles and the total number of risk factors for CIB using Bayesian hierarchical models, and on the continuous scale using Bayesian logistic regression models with interactions. Estimates were presented as posterior probability distributions of odds ratios (ORs), probabilities of different effect sizes, and marginal effects plots. We observed potential HTE for 90-day mortality according to illness severity (median subgroup OR range 0.90-1.09) with higher risk in the most severely ill, but not with different numbers of risk factors (1.00-1.02). We observed potential HTE of pantoprazole for clinically important events (0.86-1.18) and infectious adverse events (0.88-1.27) with higher risk in patients with greater illness severity and in those with more risk factors for CIB. Pantoprazole substantially and consistently reduced the risk of CIB with no indications of HTE (0.53-0.63). In this post hoc analysis of the SUP-ICU trial, we found indications of HTE with increased risks of serious adverse events in patients with greater illness severity or more risk factors for CIB allocated to pantoprazole. These findings are hypothesis-generating and warrant further prospective investigation. CLINICALTRIALS. NCT02467621.

Parathyroid Hormone Replacement versus Oral Calcium and Active Vitamin D Supplementation in Hypoparathyroidism: A Meta-analysis.

Objectives:Chronic hypoparathyroidism is treated conventionally with active vitamin D and high doses of calcium. Recombinant human parathyroid hormone (PTH) replacement is an attractive option for treating patients with hypoparathyroidism since it can replace the physiological action of native PTH. The aim of our study was to perform a comprehensive evaluation of the effects of PTH replacement on calcium homeostasis, bone metabolism, and daily requirement of calcium and active vitamin D.Materials and Methods:Randomized controlled trials done in chronic hypoparathyroid patients were included in this meta-analysis. The PTH group included subjects receiving a subcutaneous injection of either PTH (1-84) or PTH (1-34) with oral calcium and/or active vitamin D. The control group included those receiving oral calcium and active vitamin D with/without subcutaneous placebo injection. The primary outcome of this meta-analysis was to compare serum calcium, 24-h urinary calcium, and severe adverse effects among PTH and control groups.Results:In this meta-analysis, we did not find any difference in serum calcium level between PTH and control groups [mean difference (MD) - 0.01; 95% confidence interval (CI) - 0.09, 0.06; P = 0.71]. Although there was a trend towards low 24-h urinary calcium in the PTH group, the difference was not statistically significant (MD - 1.43; 95% CI - 2.89, 0.03; P = 0.06). The incidence of serious adverse events was also similar in both groups (RR 1.35; 95% CI 0.58, 3.16; P = 0.49).Conclusion:Both PTH and active vitamin D therapies are associated with comparable serum and urine calcium levels with a similar incidence of serious adverse events in patients with chronic hypoparathyroidism.

Perioperative multidisciplinary implementation enhancing recovery after hip arthroplasty in geriatrics with preoperative chronic hypoxaemia

We investigated risk factors for postoperative serious adverse events (SAEs) in elderly patients with preoperative chronic hypoxaemia undergone total hip arthroplasty (THA) or hemiarthroplasty and performed an implementation to modify and improve clinical outcome. A retrospective medical record review was performed to identify geriatric patients who receiving THA or hemiarthroplasty at a single university teaching hospital, Kunming, Yunnan, China between January 2009 and August 2017. Total of 450 elderly patients were included in the study. Data were collected on baseline characteristics, detailed treatments, and adverse events. Univariate and multivariate logistic regression analysis were used to identify risk factors for SAEs. In multivariate regression analysis, a higher occurrence of general anaesthesia and multiple episodes of hypotension were associated with higher risk of SAEs (general anesthesia: odds ratio [OR] 5.09, 95% confidence interval [CI] 1.96–13.24, P = 0.001; hypotension time: OR 4.29, 95% CI 1.66–11.10, P = 0.003). After the multidisciplinary implementation, the postoperative length of stay was decreased from 15 days to 10 days (P < 0.0001); incidence of SAEs was decreased from 21.1% to 7.0% (P = 0.002), and the all-cause mortality rate within 30 days decreased from 4.6% to 1.0% (P = 0.040). Our observational study demonstrated that an increasing application of general anaesthesia and longer time of hypotension were associated with an increased risk of postoperative SAEs in patients after THA or hemiarthroplasty. Additionally, optimizing stable haemodynamics under higher application of combined-spinal epidural anaesthesia was associated with improved outcome up to 30 days after THA or hemiarthroplasty.

A Systematic Review of Human Trials Using Stem Cell Therapy for Erectile Dysfunction.

Novel therapeutic modalities have been proposed for the treatment and management of erectile dysfunction (ED). Stem cell therapy (SCT) is the injection of mesenchymal stem cells or stromal vascular fractions from adipose and other tissue sources. Although SCT has been studied and reported in multiple rodent trials, few human clinical trials exist. The aim of this study was to provide a systematic review of SCT for the treatment of ED with an emphasis on data from peer-reviewed human studies. A systematic review was performed evaluating SCT for ED in human studies using PubMed-Medline and Scopus databases. Literature search was conducted using key words such as "Clinical Trials of SCT for ED," "Stromal Vascular Fraction Treatment for ED," and "SCT for ED." Systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The main outcomes measure was the safety and efficacy of SCT for ED in humans. 5 studies specific to SCT for ED treatment were included. A total of 61 patients were included in these phase I and II clinical trials and follow-up periods ranged from 6-62 months. End points of the studies included safety, tolerability, and efficacy of SCT for ED. The majority of the studies demonstrated improvement in erectile function due to SCT in patients, including improvements in penile vascular flow, International Index of Erectile Function-15 items, and Erectile Hardness Scale scores. All of the studies reported that there were no serious adverse events for patients. Limitations of the studies included small cohort sizes, and only 1 contained a sham arm. The 5 completed human clinical trials show promise for SCT as a restorative therapy for the treatment of ED. However, although promising, there still exists very limited data for the use of SCT for ED in humans. With the expansion of clinics offering SCT for ED, it is imperative that SCT is investigated further for safety, efficacy, and standardization. Lokeshwar SD, Patel P, Shah SM, etal. A Systematic Review of Human Trials using Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2020;8:122-130.

Efficacy and safety of direct-acting antivirals for treatment-naive patients with genotype 1 hepatitis C virus infection.

This systematic review was performed on the basis of Preferred Reporting Items for Systematic Reviews and Meta-analyses and Cochrane recommendations to compare sustained virological response (SVR12) and the serious adverse events in patients treated by directing-acting antivirals. We conducted a literature search in PubMed/Medline, EBSCO, Embase and the Cochrane Library until 2018. A consistency model was used to get the relative effect of odds ratio among regimens and the possibility for the efficacy and safety of 13 regimen, and we divided these regimens into DUAL or TRIO regimens to conduct integrated data analysis. The results demonstrated that dual or triple directing-acting antiviral-combined regimens had higher SVR12 rates, Daclatasvir plus Asunaprevir may be a good choice for genotype 1 patients, and regimens without Ribavirin and interferon are safer.

Serious adverse events in patients with target-oriented blood pressure management: a systematic review.

: On the basis of the benefits of antihypertensive treatment, progressively intensive treatment is advocated. However, it remains controversial whether intensive blood pressure control might increase the frequency of serious adverse events (SAEs) compared with moderate control. This review assessed the occurrence of SAEs in blood pressure treatment with predefined blood pressure targets. Seven original studies and eight post hoc analyses (derived from two original studies) met the inclusion criteria. Compared with moderate blood pressure treatment, intensive treatment was associated with a significant increase in treatment-related SAEs (Sign-test: P = 0.0002, Wilcoxon signed-rank test: P = 0.001). However, comparability between studies was limited, due to unclear determinations about the treatment-relatedness of adverse events, missing definitions of SAEs and variations in recording methods. Thus, a meta-analysis was not justified. The definitions of serious adverse events and methods of recording and reporting need to be improved and standardized to facilitate the comparison of results.

Medical errors: Healthcare professionals' perspective at a tertiary hospital in Kuwait.

Medical errors are of economic importance and can contribute to serious adverse events for patients. Medical errors refer to preventable events resulting from healthcare interactions, whether these events harm the patient or not. In Kuwait, there is a paucity literature detailing the causes, forms, and risks of medical errors in their state-funded healthcare facilities. This study aimed to explore medical errors, their causes and preventive strategies in a Kuwait tertiary hospital based on the perceptions and experience of a cross-section of healthcare professionals using a questionnaire with 27 open (n = 10) and closed (n = 17) questions. The recruited healthcare professionals in this study included pharmacists, nurses, physicians, dentists, radiographers, hospital administrators, surgeons, nutritionists, and physiotherapists. The collected data were analysed quantitatively using descriptive statistics. A total of 203 participants filled and completed the survey questionnaire. The frequency of medical errors in Kuwait was found to be high at 60.3% ranging from incidences of prolonged hospital stays (32.9%), adverse events and life-threatening complications (32.3%), and fatalities (20.9%). The common medical errors result from incomplete instructions, incorrect dosage, and incorrect route of administration, diagnosis errors, and labelling errors. The perceived causes of these medical errors include high workload, lack of support systems, stress, medical negligence, inadequate training, miscommunication, poor collaboration, and non-adherence to safety guidelines among the healthcare professionals.

Incidence and Risk of Glucocorticoid-Associated Adverse Effects in Patients With Rheumatoid Arthritis.

Using the UK Clinical Practice Research Datalink, we examined the incidence of glucocorticoid (GC)-related serious adverse events (SAEs) in rheumatoid arthritis (RA) and non-RA patients and quantified the risk of SAEs in patients with RA. We matched incident patients with RA to an age- and sex-matched, non-RA comparison group of equal size. In a cohort analysis, we estimated incidence rates (IRs) and IR ratios (IRRs) for GC-related AEs (i.e., diabetes mellitus [DM], osteoporosis, fractures, glaucoma, hypertension, gastrointestinal [GI] perforation or bleeding, thrombotic stroke or myocardial infarction [MI], or death), stratified by GC use. We conducted a series of nested case-control analyses among patients with RA, evaluating the effects of increasing cumulative and average daily GC dose. Cases of each outcome were matched to controls for age, sex, and general practice. We calculated adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) for each outcome. Patients with RA had a higher incidence for all investigated SAEs except glaucoma, compared to non-RA patients. IRRs were greater in those patients prescribed a GC than in those without. In patients with RA, GCs were associated with an elevated risk of DM (adjusted OR 1.33 [95% CI 1.14-1.56]), osteoporosis (adjusted OR 1.41 [95% CI 1.25-1.59]), thrombotic stroke or MI (adjusted OR 1.28 [95% CI 1.07-1.52]), serious infection (adjusted OR 1.28 [95% CI 1.11-1.48]), and death (adjusted OR 1.33 [95% CI 1.19-1.48]). There was a trend of increasing risk with increasing cumulative and average daily GC dose for all outcomes other than glaucoma, hypertension, and GI perforations or bleeding (P < 0.05). Patients with RA had an increased incidence of GC-related AEs. Increasing cumulative and average daily GC doses were found to be associated with an increasing risk of developing an AE.

Incidence of Ipilimumab-Related Serious Adverse Events in Patients with Advanced Cancer: A Meta-Analysis.

Background: Little is known about the incidence of ipilimumab-related serious adverse events (SAEs) across various tumor types, drug doses and treatment regimens.Methods: PubMed database was searched up to November, 2017 to identify prospective clinical trials of ipilimumab therapy for adult patients with cancer. Comparisons of the incidence were based on the χ2 test in univariate analysis and the logistic regression model in multivariate analysis.Results: Twenty-four studies (4549 patients) with 35 independent study cohorts (21 melanoma, 6 prostate cancer, 5 NSCLC, and 3 SCLC cohorts) of ipilimumab were included in the meta-analysis. The overall incidence of SAEs during ipilimumab mono-therapy was 26.1% (95% CI, 21.1%-31.8%). SAEs were more frequent in the 10 mg/kg groups than in the 3 mg/kg groups (35.9% vs 17.3%; P < 0.001). Combination therapy showed significantly higher incidence than mono-therapy in melanoma (33.8% vs 25.0%; P = 0.002). After adjustment for potential confounders, multivariable analyses demonstrated lower odds of SAEs in NSCLC (odds ratio [OR] 0.52, 95% CI 0.40-0.69, P < 0.001) and SCLC (OR 0.41, 95% CI 0.31-0.54, P < 0.001) compared with melanoma. The 10mg/kg cohort presented significantly higher odds than the 3mg/kg (OR 2.84, 95% CI 2.35-3.43, P < 0.001). The combination therapy showed significantly higher odds than the mono-therapy (OR 1.38, 95% CI 1.11-1.71, P = 0.003).Conclusions: The incidence of ipilimumab-related SAEs was higher in melanoma, the 10mg/kg group and during combination therapy. Clinicians should enhance awareness of these risk factors in clinical practice and carefully monitor patients.

Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis

BackgroundTyrosine kinase 2 (TYK2) signaling pathways, which mediate cytokine signaling, are implicated in the pathophysiology of psoriasis. Selective inhibitors of TYK2 may be effective in treating psoriasis.MethodsWe conducted a phase 2, double-blind trial of a TYK2 inhibitor, BMS-986165, in adults with moderate-to-severe psoriasis, excluding patients with a previous lack of response to agents targeting cytokine signaling through the same tyrosine kinase pathway. Patients were randomly assigned to receive the drug orally at a dose of 3 mg every other day, 3 mg daily, 3 mg twice daily, 6 mg twice daily, or 12 mg daily or to receive placebo. The primary end point was a 75% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12 (higher scores indicate greater severity of psoriasis).ResultsA total of 267 patients received at least one dose in an intervention group of the trial. At week 12, the percentage of patients with a 75% or greater reduction in the PASI score was 7% (3 of 45 patients) with placebo, 9% (4 of 44 patients) with 3 mg of BMS-986165 every other day (P=0.49 vs. placebo), 39% (17 of 44 patients) with 3 mg daily (P<0.001 vs. placebo), 69% (31 of 45 patients) with 3 mg twice daily (P<0.001 vs. placebo), 67% (30 of 45 patients) with 6 mg twice daily (P<0.001 vs. placebo), and 75% (33 of 44 patients) with 12 mg daily (P<0.001 vs. placebo). There were three serious adverse events in patients receiving the active drug, as well as one case of malignant melanoma 96 days after the start of treatment.ConclusionsSelective inhibition of TYK2 with the oral agent BMS-986165 at doses of 3 mg daily and higher resulted in greater clearing of psoriasis than did placebo over a period of 12 weeks. Larger and longer-duration trials of this drug are required to determine its safety and durability of effect in patients with psoriasis. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT02931838.)

Novel Approach Leveraging Social Media Indicates Complementary and Alternative Medicine Use Highly Prevalent and Is Sometimes Associated with Serious Adverse Events in Patients With Autoimmune Hepatitis

Introduction: The use of CAM by patients with chronic liver disease has been explored, but the use of CAM products by patients with autoimmune hepatitis (AIH) is unknown. We sought to investigate the frequency and characteristics of CAM use by patients with AIH by interrogating two large and interactive AIH-specific social media groups. Methods: An invitation to complete a CAM-specific questionnaire was posted every other day to wellestablished autoimmune hepatitis Facebook communities (AHRN and AIHA) during a 10 day study period. Combined membership of these two closed social media groups was 2600 individuals with AIH. The survey contained 22 questions and collected patient demographics, disease characteristics, and CAM use. Age ≥ 18 years and an AIH diagnosis by an MD were the eligibility criteria. Results: A total of 401 individuals with AIH completed the questionnaire. Respondents were 91% female with average age at survey completion of 49.3 yrs and average age at AIH diagnosis of 42.9 yrs. 36% reported early fibrosis and 37% advanced fibrosis on liver biopsy nearest to their diagnosis. 90% were currently treated for AIH including 41% on prednisone, 11% budesonide, 69% thiopurines, and 15% purine analogues. 246 (61%) respondents reported any CAM during their lifetime; while 220 (55%) reported CAM use prior to and 193 (48%) after their AIH diagnosis. The most common reasons for CAM prior to their diagnosis was overall health improvement (77%), better sleep (27%), and weight loss (23%). The most common reasons for CAM use after AIH diagnosis was overall health improvement (56%), immune support (32%), and joint pain (29%). Eighty five (44%) respondents who used CAM after their diagnosis reported using CAM to treat AIH related symptoms, most commonly joint pain (94%), fatigue (86%), and sleep disturbances (78%). The CAM use after diagnosis was associated with younger age at diagnosis (41.5 yrs vs. 44 yrs, p=0.04) and higher education (college or more) (84% vs 16%) (p=0.001), but not gender, current age, liver fibrosis or medications. Ten (4%) CAM users reported severe adverse events (SAEs), 10 (4%) emergency room visits secondary to CAM and 3 (1%) requiring hospitalization. Headaches, worsening fatigue/joint pain, and gastrointestinal symptoms were the most common SAEs. Conclusion: There is high prevalence of CAM use among patients with AIH and their use is associated with younger age and higher education. Nearly 5% of CAM users reported SAEs with 1% requiring hospitalization.

Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia

The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6]). Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm. ClinicalTrials.gov Identifier: NCT01191840.

Safety of endobronchial ultrasound-guided transbronchial needle aspiration in patients with lung cancer within a year after percutaneous coronary intervention.

BackgroundEndobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) may be necessary for patients with incidental lung cancer during or after coronary intervention. Although EBUS‐TBNA is quite safe, the safety in patients who recently received percutaneous coronary intervention (PCI) has not been demonstrated. The aim of this study was to assess the safety of EBUS‐TBNA in patients with lung cancer who underwent PCI within one year.MethodsWe retrospectively reviewed the medical records of 24 patients who underwent EBUS‐TBNA within one year after PCI between May 2009 and June 2017. Cardiovascular complications (death, myocardial infarction, arrhythmia, and acute heart failure) were assessed as primary outcomes. Procedural‐related complications were assessed as secondary outcomes.ResultsThe coronary artery diseases requiring PCI were: myocardial infarction (n = 10), unstable angina (n = 10), stable angina (n = 2), and silent ischemia (n = 2). The median interval between PCI and EBUS‐TBNA was 125 days (interquartile range: 66–180). Atrial fibrillation with a rapid ventricular response temporarily occurred in one patient after EBUS‐TBNA. No other significant cardiovascular complications were encountered. Fifteen patients were administered an anti‐thrombotic agent the day of EBUS‐TBNA, while four had ceased taking the agent < 4 days before EBUS‐TBNA, however, there was no significant bleeding among those patients.ConclusionEBUS‐TBNA was safe and did not cause serious adverse events in patients with lung cancer who required tissue confirmation or mediastinal staging within one year after PCI. Incidental lung cancer found during or after a coronary intervention should be actively evaluated by EBUS‐TBNA.

Prevalence and outcome of heparin-induced thrombocytopenia diagnosed under veno-arterial extracorporeal membrane oxygenation: a retrospective nationwide study.

Thrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to postcardiac surgery patients, heparin-induced thrombocytopenia (HIT) could represent the causative underlying mechanism. However, the epidemiology as well as related mortality regarding HIT and VA-ECMO remains largely unknown. We aimed to define the prevalence and associated 90-day mortality of HIT diagnosed under VA-ECMO. This retrospective study included patients under VA-ECMO from 20 French centers between 2012 and 2016. Selected patients were hospitalized for more than 3days with high clinical suspicion of HIT and positive anti-PF4/heparin antibodies. Patients were classified according to results of functional tests as having either Confirmed or Excluded HIT. A total of 5797 patients under VA-ECMO were screened; 39/5797 met the inclusion criteria, with HIT confirmed in 21/5797 patients (0.36% [95% CI] [0.21-0.52]). Fourteen of 39 patients (35.9% [20.8-50.9]) with suspected HIT were ultimately excluded because of negative functional assays. Drug-induced thrombocytopenia tended to be more frequent in Excluded HIT at the time of HIT suspicion (p = 0.073). The platelet course was similar between Confirmed and Excluded HIT (p = 0.65). Mortality rate was 33.3% [13.2-53.5] in Confirmed and 50% [23.8-76.2] in Excluded HIT (p = 0.48). Prevalence of HIT among patients under VA-ECMO is extremely low at 0.36% with an associated mortality rate of 33.3%, which appears to be in the same range as that observed in patients treated with VA-ECMO without HIT. In addition, HIT was ultimately ruled out in one-third of patients with clinical suspicion of HIT and positive anti-PF4/heparin antibodies.

Endoscopic sinusotomy versus redo surgery for the treatment of chronic pouch anastomotic sinus in ulcerative colitis patients

Pouch sinus may be a serious adverse event in patients undergoing ileal pouch-anal anastomosis. The aim of this study was to compare endoscopic sinusotomy (ESi) and redo pouch surgery in the management of pouch sinus. All consecutive ulcerative colitis patients with chronic pouch sinuses treated with ESi versus redo surgery from 2006 to 2016 were identified. The primary outcomes were recurrence-free and surgery-free survivals. The secondary outcome was postprocedural adverse events. This historical cohort study included 226 patients (ESi, n= 141; redo surgery, n= 85). Complete healing of the sinus was achieved in 75 patients (53.2%) and partial healing in 23 patients (16.3%) with ESi, and an initial complete healing (ie, no anastomotic leak before ileostomy closure) was obtained in 80 patients (94.1%) receiving redo surgery. Sinus recurrence after complete healing was seen in 17 patients (22.7%) treated with ESi and 28 patients (32.9%) treated with surgery (P= .15). Subsequent surgery was needed in 34 patients (24.1%) with ESi therapy and 18 patients (21.2%) with initial redo surgery (P= .70). Kaplan-Meier recurrence-free and surgery-free survivals after initial procedures showed no statistical difference between the 2 groups (P= .42 and P= .65, respectively). The rate of adverse events in the ESi group was significantly lower than that in the surgery group (2.5% vs 43.5%, P< .0001). Recurrence-free and surgery-free survivals were comparable between patients treated with ESi and redo surgery, whereas pouch redo surgery was found to be associated with a higher immediate complete healing rate yet a higher morbidity.

National Early Warning Score Accurately Discriminates the Risk of Serious Adverse Events in Patients With Liver Disease

The National Early Warning Score (NEWS) is used to identify deteriorating adult hospital inpatients. However, it includes physiological parameters frequently altered in patients with cirrhosis. We aimed to assess the performance of the NEWS in acute and chronic liver diseases. We collected vital signs, recorded in real time, from completed consecutive admissions of patients 16 years or older to a large acute-care hospital in Southern England, from January 1, 2010, through October 31, 2014. Using International Classification of Diseases, 10th revision, codes, we categorized patients as having primary liver disease, secondary liver disease, or none. For patients with liver disease, 2 analysis groups were developed: the first was based on clinical group (such as acute or chronic, alcohol-induced, or associated with portal hypertension), and the second was based on a summary of liver-related, hospital-level mortality indicator diagnoses. For each, we compared the abilities of the NEWS and 34 other early warning scores to discriminate 24-hour mortality, cardiac arrest, or unanticipated admission to the intensive care unit using the area under the receiver operating characteristic (AUROC) curve and early warning score efficiency curve analyses. The NEWS identified patients with primary, nonprimary, and no diagnoses of liver disease with AUROC values of 0.873 (95% CI, 0.860-0.886), 0.898 (95% CI, 0.891-0.905), and 0.879 (95% CI, 0.877-0.881), respectively. High AUROC values were also obtained for all clinical subgroups; the NEWS identified patients with alcohol-related liver disease with an AUROC value of 0.927 (95% CI, 0.912-0.941). The NEWS identified patients with liver diseases with higher AUROC values than other early warning scoring systems. The NEWS accurately discriminates patients at risk of death, admission to the intensive care unit, or cardiac arrest within a 24-hour period for a range of liver-related diagnoses. Its widespread use provides a ready-made, easy-to-use option for identifying patients with liver disease who require early assessment and intervention, without the need to modify parameters, weightings, or escalation criteria.

Subdural hematomas in 1846 patients with shunted idiopathic normal pressure hydrocephalus: treatment and long-term survival.

OBJECTIVE Subdural hematoma (SDH) is the most common serious adverse event in patients with shunts. Adjustable shunts are used with increasing frequency and make it possible to noninvasively treat postoperative SDH. The objective of this study was to describe the prevalence and treatment preferences of SDHs, based on fixed or adjustable shunt valves, in a national cohort of patients with shunted idiopathic normal pressure hydrocephalus (iNPH), as well as to evaluate the effect of SDH and treatment on long-term survival. METHODS Patients with iNPH who received a CSF shunt in Sweden from 2004 to 2015 were included in a prospective quality registry (n = 1846) and followed regarding SDH, its treatment, and mortality. The treatment of SDH was categorized into surgery, opening pressure adjustments, or no treatment. RESULTS During the study period, the proportion of adjustable shunts increased from 75% to 95%. Ten percent (n = 184) of the patients developed an SDH. In 103 patients, treatment was solely opening pressure adjustment. Surgical treatment was used in 66 cases (36%), and 15 (8%) received no treatment. In patients with fixed shunt valves, 90% (n = 17) of SDHs were treated surgically compared with 30% (n = 49) in patients with adjustable shunts (p < 0.001). There was no difference in long-term patient survival between the SDH and non-SDH groups or between different treatments. CONCLUSIONS SDH remains a common complication after shunt surgery, but adjustable shunts reduced the need for surgical interventions. SDH and treatment did not significantly affect survival in this patient group, thus the noninvasive treatment offered by adjustable shunts considerably reduces the level of severity for this common adverse event.

The effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and Trial Sequential Analysis.

BackgroundAtrial fibrillation and atrial flutter may be managed by either a rhythm control strategy or a rate control strategy but the evidence on the clinical effects of these two intervention strategies is unclear. Our objective was to assess the beneficial and harmful effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter.MethodsWe searched CENTRAL, MEDLINE, Embase, LILACS, Web of Science, BIOSIS, Google Scholar, clinicaltrials.gov, TRIP, EU-CTR, Chi-CTR, and ICTRP for eligible trials comparing any rhythm control strategy with any rate control strategy in patients with atrial fibrillation or atrial flutter published before November 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were stroke and ejection fraction. We performed both random-effects and fixed-effect meta-analysis and chose the most conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. Statistical heterogeneity was assessed by visual inspection of forest plots and by calculating inconsistency (I2) for traditional meta-analyses and diversity (D2) for TSA. Sensitivity analyses and subgroup analyses were conducted to explore the reasons for substantial statistical heterogeneity. We assessed the risk of publication bias in meta-analyses consisting of 10 trials or more with tests for funnel plot asymmetry. We used GRADE to assess the quality of the body of evidence.Results25 randomized clinical trials (n = 9354 participants) were included, all of which were at high risk of bias. Meta-analysis showed that rhythm control strategies versus rate control strategies significantly increased the risk of a serious adverse event (risk ratio (RR), 1.10; 95% confidence interval (CI), 1.02 to 1.18; P = 0.02; I2 = 12% (95% CI 0.00 to 0.32); 21 trials), but TSA did not confirm this result (TSA-adjusted CI 0.99 to 1.22). The increased risk of a serious adverse event did not seem to be caused by any single component of the composite outcome. Meta-analysis showed that rhythm control strategies versus rate control strategies were associated with better SF-36 physical component score (mean difference (MD), 6.93 points; 95% CI, 2.25 to 11.61; P = 0.004; I2 = 95% (95% CI 0.94 to 0.96); 8 trials) and ejection fraction (MD, 4.20%; 95% CI, 0.54 to 7.87; P = 0.02; I2 = 79% (95% CI 0.69 to 0.85); 7 trials), but TSA did not confirm these results. Both meta-analysis and TSA showed no significant differences on all-cause mortality, SF-36 mental component score, Minnesota Living with Heart Failure Questionnaire, and stroke.ConclusionsRhythm control strategies compared with rate control strategies seem to significantly increase the risk of a serious adverse event in patients with atrial fibrillation. Based on current evidence, it seems that most patients with atrial fibrillation should be treated with a rate control strategy unless there are specific reasons (e.g., patients with unbearable symptoms due to atrial fibrillation or patients who are hemodynamically unstable due to atrial fibrillation) justifying a rhythm control strategy. More randomized trials at low risk of bias and low risk of random errors are needed.Trial registrationPROSPERO CRD42016051433

Drug-eluting bead transarterial chemoembolization in the treatment for unresectable soft tissue sarcoma refractory to systemic chemotherapy: a preliminary evaluation of efficacy and safety.

To preliminarily evaluate the clinical efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) for unresectable soft tissue sarcoma refractory to systemic chemotherapy. Ten patients with refractory sarcoma who underwent DEB-TACE therapy between January 2015 and January 2017 were identified. Clinical information and radiological data were retrospectively collected to analyze tumor response, overall survival (OS), progression-free survival and adverse events (AEs). Tumor response to DEB-TACE was assessed with modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. All DEB-TACE procedures were successfully performed for ten patients with 15 tumor lesions. The median follow-up duration was 19months and the median survival time was 21months (range 11-30months). The 1- and 2-year OS rate was 90 and 30%, respectively. According to the guidance of mRECIST, complete response, partial response, stable disease and progressive disease were noted in zero (0%), three (30%), four (40%) and three (30%) patients, respectively. The disease control rate and objective response rate was 70 and 30%, respectively. There were no serious AEs in patients after DEB-TACE. Our data showed that DEB-TACE was effective and safe for patients with soft tissue sarcoma. Therefore, DEB-TACE can be considered as an alternative treatment option for unresectable soft tissue sarcoma refractory to conventionally systemic chemotherapy.

Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial

SummaryBackgroundFor many years, first-line treatment for locally advanced or metastatic soft-tissue sarcoma has been doxorubicin. This study compared gemcitabine and docetaxel versus doxorubicin as first-line treatment for advanced or metastatic soft-tissue sarcoma.MethodsThe GeDDiS trial was a randomised controlled phase 3 trial done in 24 UK hospitals and one Swiss Group for Clinical Cancer Research (SAKK) hospital. Eligible patients had histologically confirmed locally advanced or metastatic soft-tissue sarcoma of Trojani grade 2 or 3, disease progression before enrolment, and no previous chemotherapy for sarcoma or previous doxorubicin for any cancer. Patients were randomly assigned 1:1 to receive six cycles of intravenous doxorubicin 75 mg/m2 on day 1 every 3 weeks, or intravenous gemcitabine 675 mg/m2 on days 1 and 8 and intravenous docetaxel 75 mg/m2 on day 8 every 3 weeks. Treatment was assigned using a minimisation algorithm incorporating a random element. Randomisation was stratified by age (≤18 years vs >18 years) and histological subtype. The primary endpoint was the proportion of patients alive and progression free at 24 weeks in the intention-to-treat population. Adherence to treatment and toxicity were analysed in the safety population, consisting of all patients who received at least one dose of their randomised treatment. The trial was registered with the European Clinical Trials (EudraCT) database (no 2009–014907–29) and with the International Standard Randomised Controlled Trial registry (ISRCTN07742377), and is now closed to patient entry.FindingsBetween Dec 3, 2010, and Jan 20, 2014, 257 patients were enrolled and randomly assigned to the two treatment groups (129 to doxorubicin and 128 to gemcitabine and docetaxel). Median follow-up was 22 months (IQR 15·7–29·3). The proportion of patients alive and progression free at 24 weeks did not differ between those who received doxorubicin versus those who received gemcitabine and docetaxel (46·3% [95% CI 37·5–54·6] vs 46·4% [37·5–54·8]); median progression-free survival (23·3 weeks [95% CI 19·6–30·4] vs 23·7 weeks [18·1–20·0]; hazard ratio [HR] for progression-free survival 1·28, 95% CI 0·99–1·65, p=0·06). The most common grade 3 and 4 adverse events were neutropenia (32 [25%] of 128 patients who received doxorubicin and 25 [20%] of 126 patients who received gemcitabine and docetaxel), febrile neutropenia (26 [20%] and 15 [12%]), fatigue (eight [6%] and 17 [14%]), oral mucositis (18 [14%] and two [2%]), and pain (ten [8%] and 13 [10%]). The three most common serious adverse events, representing 111 (39%) of all 285 serious adverse events recorded, were febrile neutropenia (27 [17%] of 155 serious adverse events in patients who received doxorubicin and 15 [12%] of 130 serious adverse events in patients who received gemcitabine and docetaxel, fever (18 [12%] and 19 [15%]), and neutropenia (22 [14%] and ten [8%]). 154 (60%) of 257 patients died in the intention-to-treat population: 74 (57%) of 129 patients in the doxorubicin group and 80 (63%) of 128 in the gemcitabine and docetaxel group. No deaths were related to the treatment, but two deaths were due to a combination of disease progression and treatment.InterpretationDoxorubicin should remain the standard first-line treatment for most patients with advanced soft-tissue sarcoma. These results provide evidence for clinicians to consider with their patients when selecting first-line treatment for locally advanced or metastatic soft-tissue sarcoma.FundingCancer Research UK, Sarcoma UK, and Clinical Trial Unit Kantonsspital St Gallen.