Risk Of Overall Adverse Events Research Articles

Adverse Events Associated With Therapeutic Endoscopic Retrograde Pancreatography.

Data regarding the safety of endoscopic retrograde pancreatography (ERP) are limited compared with biliary endoscopic retrograde cholangiopancreatography. The aim of this study was to determine adverse events (AEs) associated with therapeutic ERP. This single-center retrospective study examined consecutive therapeutic ERPs with the primary intention of cannulating the pancreatic duct. Multivariate logistic regression was performed to identify risk factors for AEs. A total of 3023 ERPs were performed in 1288 patients (mean age, 50.3 years; 57.8% female) from January 2000 to January 2017. Overall AE rate was 18.9% with abdominal pain requiring admission (9.8%) and post-ERP pancreatitis (5.7%) being most common. On multivariate analysis, female sex (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.9-2.9), acute recurrent pancreatitis (aOR, 5.0; 95% CI, 1.7-15.3), chronic pancreatitis (aOR, 1.8; 95% CI, 1.3-2.6), and pancreatic sphincter of Oddi dysfunction (aOR, 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of overall AEs. Pancreatic sphincterotomy (aOR, 1.9; 95% CI, 1.5-2.4) and therapeutic stenting (aOR, 1.6; 95% CI, 1.2-2.2) also increased the risk of AEs. Nearly 1 in 5 patients who undergo therapeutic ERP will experience an AE; however, the rates of major AEs, including post-ERP pancreatitis, bleeding, and perforation, are low.

Retrospective analysis of safety of ultrasound-guided percutaneous liver biopsy in the 21st century.

Ultrasound-guided percutaneous liver biopsy is a standard procedure, but it might be burdened with serious adverse events, mainly hemorrhagic. Literature lacks recent studies taking into account new ultrasound machines, more sensitive to tiny vessels and the evolution of the bioptic technique, including ultrasound guidance in all instances. Hence, the primary aim of this study was to evaluate complication rates of ultrasound-guided percutaneous liver biopsy in a recent population. Secondary aims were to evaluate if the experience of operator is a determinant of risk of complication and to identify other potential risk factors. We evaluated 800 procedures carried out in one hospital in the period 2010-2018. Complication rate resulted in 4%, with the occurrence of moderate hemorrhagic complications in 0.75%. No cases of severe events or death were registered. A higher risk of bleeding was found to be associated with less experienced operators, while the need to perform multiple needle insertions increased the probability of adverse events. The present findings confirmed ultrasound-guided percutaneous liver biopsy to be a substantially safe procedure with a low risk of overall adverse events and bleeding in particular, especially when performed by expert operators.

Effect on health-related quality of life of the X-Bolt dynamic plating system versus the sliding hip screw for the fixation of trochanteric fractures of the hip in adults: the WHiTE Four randomized clinical trial

AimsSurgical treatment of hip fracture is challenging; the bone is porotic and fixation failure can be catastrophic. Novel implants are available which may yield superior clinical outcomes. This study compared the clinical effectiveness of the novel X-Bolt Hip System (XHS) with the sliding hip screw (SHS) for the treatment of fragility hip fractures.MethodsWe conducted a multicentre, superiority, randomized controlled trial. Patients aged 60 years and older with a trochanteric hip fracture were recruited in ten acute UK NHS hospitals. Participants were randomly allocated to fixation of their fracture with XHS or SHS. A total of 1,128 participants were randomized with 564 participants allocated to each group. Participants and outcome assessors were blind to treatment allocation. The primary outcome was the EuroQol five-dimension five-level health status (EQ-5D-5L) utility at four months. The minimum clinically important difference in utility was pre-specified at 0.075. Secondary outcomes were EQ-5D-5L utility at 12 months, mortality, residential status, mobility, revision surgery, and radiological measures.ResultsOverall, 437 and 443 participants were analyzed in the primary intention-to-treat analysis in XHS and SHS treatment groups respectively. There was a mean difference of 0.029 in adjusted utility index in favour of XHS with no evidence of a difference between treatment groups (95% confidence interval -0.013 to 0.070; p = 0.175). There was no evidence of any differences between treatment groups in any of the secondary outcomes. The pattern and overall risk of adverse events associated with both treatments was similar.ConclusionAny difference in four-month health-related quality of life between the XHS and SHS is small and not clinically important. There was no evidence of a difference in the safety profile of the two treatments; both were associated with lower risks of revision surgery than previously reported.Cite this article: Bone Joint J 2021;103-B(2):256–263.

Comparative efficacy and safety of hypnotics for insomnia in older adults: a systematic review and network meta-analysis.

To compare the efficacy and safety of various hypnotics for identifying the best treatments for insomnia in older adults. We searched the EMBASE, PubMed, ClinicalTrials.gov, and ProQuest Dissertations and Theses A&I databases from the inception to September 12, 2020. Only randomized controlled trials comparing hypnotics with either another hypnotic or placebo for insomnia treatment in elderly people were included. Sleep outcomes, including total sleep time, sleep onset latency, wake after sleep onset, sleep efficiency, were derived from polysomnography, valid questionnaires, or sleep diaries. We identified 24 articles with 5917 older adults. Eszopiclone and low-dose doxepin were ranked the optimal therapy for prolonging objective and subjective total sleep time (26.69 and 28.19 min), respectively, compared to placebo. Zaleplon was the most effective therapy in reducing objective and subjective sleep onset latency (-21.63 and -15.86 min) compared with control. Temazepam was the best treatment for objective and subjective wake after sleep onset (-25.29 and -22.25 min) compared with control. Low-dose doxepin appeared to be the effective treatment for increasing objective sleep efficiency (6.08%) Triazolam showed the higher risk of overall adverse events (odds ratio, 1.96, 95% confidence interval 1.03-3.74) when compared to zaleplon. Considering study quality and the potential adverse effects of benzodiazepines and nonbenzodiazepines, low-dose doxepin seems to be the optimal pharmacotherapy for the improvements in total sleep time and sleep efficiency. Future RCTs investigating the treatment effects of hypnotics, particularly low-dose doxepin, on insomnia in older adults are warranted. PROSPERO Registration number: CRD42016046301.

Efficacy and safety of bempedoic acid in patients with hypercholesterolemia: A systematic review and meta-analysis of randomized controlled trials.

Bempedoic acid is a novel oral drug, which has been increasingly researched to play an important role in the treatment of hypercholesterolemia recently. However, results from original studies were inconsistent and inconclusive. We aimed to conduct a meta-analysis to quantitatively appraise the efficacy and safety of bempedoic acid. PubMed, Embase, Web of Science and Scopus were searched from inception to 30 January 2020. We included randomized controlled trials that compared the efficacy and safety of bempedoic acid with placebo in patients with hypercholesterolemia. Results from trials were presented as mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled by random or fixed effects model. The risk of bias and heterogeneity among trials were also assessed and analyzed. Pooled analysis of 10 eligible trials showed that bempedoic acid treatment resulted in greater lowering of the low-density lipoprotein cholesterol level than the placebo group (mean difference -23.16%, 95% CI -26.92% to -19.04%). We also found that improvements in lipid parameters and biomarkers were still maintained at weeks 24 and 52 from the long-term trials. As for safety, bempedoic acid did not increase the risk of overall adverse events (OR 1.02, 95% CI 0.88 to 1.18). However, the incidence of adverse events leading to discontinuation was higher in the bempedoic acid group (OR 1.44, 95% CI 1.14 to 1.82). Available evidence from randomized controlled trials suggests that bempedoic acid provides a well-tolerated and effective therapeutic option for lipid lowering in patients with hyperlipidemia.

Temporal trends in pharmacologic prophylaxis for venous thromboembolism after hip and knee replacement in older adults.

Trends in prescription for venous thromboembolism (VTE) prophylaxis following total hip (THR) and knee replacement (TKR) since the approval of direct oral anticoagulants (DOACs) and the 2012 guideline endorsement of aspirin are unknown, as are the risks of adverse events. We examined practice patterns in the prescription of prophylaxis agents and the risk of adverse events during the in-hospital period (the 'in-hospital sample') and 90 days following discharge (the 'discharge sample') among adults aged ⩾ 65 undergoing THR and TKR in community hospitals in the Institute for Health Metrics database over a 30-month period during 2011 to 2013. Eligible medications included fondaparinux, DOACs, low molecular weight heparin (LMWH), other heparin products, warfarin, and aspirin. Outcomes were validated by physician review of source documents: VTE, major hemorrhage, cardiovascular events, and death. The in-hospital and the discharge samples included 10,503 and 5722 adults from 65 hospitals nationwide, respectively (mean age 73, 74 years; 61%, 63% women). Pharmacologic prophylaxis was near universal during the in-hospital period (93%) and at discharge (99%). DOAC use increased substantially and was the prophylaxis of choice for nearly a quarter (in-hospital) and a third (discharge) of the patients. Aspirin was the sole discharge prophylactic agent for 17% and 19% of patients undergoing THR and TKR, respectively. Warfarin remained the prophylaxis agent of choice for patients aged 80 years and older. The overall risk of adverse events was low, at less than 1% for both the in-hospital and discharge outcomes. The low number of adverse events precluded statistical comparison of prophylaxis regimens.

Efficacy of calcitonin for treating acute pain associated with osteoporotic vertebral compression fracture: an updated systematic review.

Acutely painful osteoporotic vertebral compression fractures are associated with hospitalization and mortality in older adults. Calcitonin may be an alternative to opioid or nonopioid analgesia for treating acute compression fracture pain in emergency and primary care settings. This review summarizes pain, function, and adverse events associated with calcitonin. We searched MEDLINE, EMBASE, The Cochrane Library, clinical trials registries, and reference lists of included studies. Eligible studies evaluated the effect of synthetic calcitonins (salmon, eel, and human) on pain scores in adults ≥60 years old with a recent atraumatic compression fracture. Two reviewers screened studies, extracted data, and allocated bias in duplicate. A random effects meta-analysis evaluated standard mean difference (SMD) and heterogeneity (I2). Of 1,198 articles screened, 11 were included (9 in the meta-analysis). Treatment lasted from 14 days to 6 months. Pain was lower in the salmon calcitonin group (100-200 IU IM or NAS, daily) than the control group with high certainty of evidence at week 1 (SMD, -1.54; 95% confidence interval [CI], -2.02 - -1.06; I2 = 52%), representing a number needed to treat of two. The analgesic efficacy of salmon calcitonin at 4 weeks was unclear due to substantial heterogeneity. There was low certainty evidence that calcitonin did not increase the overall risk of adverse events, including nausea and vomiting (risk ratio, 2.10; 95% CI, 0.87-5.08; I2 = 47%). Calcitonin is beneficial and appears safe for treating acute pain associated with compression fractures. Further studies may improve the certainty of evidence.

Sulodexide for the Symptoms and Signs of Chronic Venous Disease: A Systematic Review and Meta-analysis.

IntroductionChronic venous disease (CVD) is a common condition associated with valvular dysfunction, venous hypertension and endothelial inflammation. Sulodexide facilitates the healing of venous ulcers and is frequently used in patients with CVD without ulcer. This review assessed the efficacy and safety of sulodexide for treatment of signs and symptoms of lower extremity CVD.MethodsWe searched MEDLINE, EMBASE, CINAHL and AMED as well as the Cochrane Central Register of Controlled Trials and the World Health Organisation (WHO) International Clinical Trials Registry Platform Search Portal. We also manually searched potentially relevant journals, conference proceedings and journal supplements. Any study monitoring any effect of sulodexide in patients with CVD at any stage of the disease, classified or non-classified, was considered. Treatment effects were estimated using standardised mean differences (SMDs), mean differences (MDs) and risk ratios (RRs), as appropriate. We calculated 95% confidence intervals (CIs) and heterogeneity (Q, tau and I2).ResultsThe search found 64 studies, but only 23 provided data on 7153 participants (mean age 55 years; 68% female). The 13 studies providing extractable quantitative information included 1901 participants (mean age 55.2 years; 65% female). Sulodexide decreased the intensity of pain, cramps, heaviness, oedema and total symptom score and reduced inflammatory mediators in patients with CVD. The risk of adverse events (AEs) was not different between sulodexide and placebo or heparan sulphate (RR 1.31, 95% CI 0.74–2.32; I2 = 0%; 270 participants). The overall risk of AEs with sulodexide was low: 3% (95% CI 1–4%) estimated from 3656 participants.ConclusionSulodexide was found to have a beneficial venoactive effect on the major signs and symptoms of CVD such as pain, cramps, heaviness and oedema without increasing the risk of AEs. It is also likely to exert a systemic effect on the course of CVD by interfering with inflammatory chemokines.

Hyaluronic Acid Injections or Oral Nonsteroidal Anti-inflammatory Drugs for Knee Osteoarthritis: Systematic Review and Meta-analysis of Randomized Trials

Background:Intra-articular hyaluronic acid (HA) injections and oral nonsteroidal anti-inflammatory drugs (NSAIDs) are common treatments for symptomatic knee osteoarthritis (OA). However, the comparative effects of these treatments are unclear.Purpose:To compare the efficacy and safety of intra-articular HA injections compared with oral NSAIDs for the treatment of knee OA.Study Design:Systematic review; Level of evidence, 1.Methods:We systematically searched Medline, Embase, and the Cochrane Central Register of Controlled Trials for randomized trials of knee OA treatment with HA injections compared with oral NSAIDs. The main outcomes were knee pain, knee function, adverse events (AEs), serious AEs, study withdrawals, and study withdrawals because of AEs. Pooled effect sizes were reported at the final follow-up with standardized mean difference (SMD) for efficacy outcomes and risk ratio (RR) for safety outcomes.Results:In 6 randomized trials of 831 patients (414 HA, 417 NSAIDs), with follow-up ranging from 5 to 26 weeks, HA injections were associated with small, statistically significant improvements in knee pain (SMD, 0.15; P = .04) and knee function (SMD, 0.23; P = .01) compared with oral NSAIDs. The risk of AEs was lower with HA compared with NSAIDs (19.8% vs 29.0%; RR, 0.74; P = .01). The risk of a serious AE (RR, 1.37; P = .71), study withdrawal (RR, 1.05; P = .68), or study withdrawal because of an AE (RR, 0.65; P = .22) was comparable between groups. Gastrointestinal concerns were the most frequent AE reported, occurring more often with NSAIDs (23.4% vs 14.1%; P = .001). AEs reported more frequently with HA injections were injection site pain (11.7% vs 4.7%; P < .001), headache (8.4% vs 4.4%; P = .03), and arthralgia (8.1% vs 2.9%; P = .001). Significant heterogeneity or publication bias was not observed for any outcome.Conclusion:Comparing short-term outcomes of HA injections with oral NSAIDs for treatment of knee OA, HA injections provided statistically significant but not clinically important improvements in knee pain and function, along with a lower overall risk of AEs.

Comparative Efficacy and Safety of Hypnotics for Insomnia in Older Adults: A Systematic Review and Network Meta-Analysis

Background: Hypnotics, such as benzodiazepines and nonbenzodiazepines, have been used to aid sleep and treat insomnia in older adults. However, there is limited information for the comparative efficacy and safety of different hypnotics for insomnia in older adults. Methods: EMBASE, PubMed, ClinicalTrials.gov, and ProQuest Dissertations and Theses A&I databases were searched. We included randomised controlled trials comparing hypnotics with either another hypnotic or placebo for insomnia treatment in elderly people. A multivariate random effect network meta-analysis in a frequentist framework was used for estimations of treatment effects and safety. Findings: Twenty-two articles with 5172 older adults were included. Eszopiclone was ranked as the best therapy for prolonging objective total sleep time (28·60 mins), and low-dose doxepin appeared to be the optimal treatment for increasing subjective total sleep time (28·19 mins) and objective sleep efficiency (6.8%) compared with control. Zaleplon was the most effective therapy in reducing objective and subjective sleep onset latency (-21·63 mins and -15·92 mins) compared with control. The risk of overall adverse events was highest with triazolam use (odd ratio, 1·89, 95% confidence interval 1·10 to 3·25) compared to placebo. Interpretation: Considering unclear risk of bias and the potential adverse effects of benzodiazepines and nonbenzodiazepines, we suggest that low-dose doxepin can be the optimal pharmacotherapy for the improvements of sleep duration and sleep efficiency. Future RCTs investigating the treatment effects of hypnotics, particularly low-dose doxepin, on insomnia in older adults are warranted. Funding Statement: HYC acknowledges the support of the Taiwan Ministry of Science and Technology (MOST 106-2314-B-038 -058 -MY3). YKT was supported by the Ministry of Science and Technology, Taiwan (MOST 106-2314-B-002 -098 -MY3). Declaration of Interests: All authors declared no conflicts of interest in this work. Ethics Approval Statement: The study is registered with PROSPERO, number CRD42016046301.

Complications and Adverse Events of Three Magnetic Resonance Imaging–based Target Biopsy Techniques in the Diagnosis of Prostate Cancer Among Men with Prior Negative Biopsies: Results from the FUTURE Trial, a Multicentre Randomised Controlled Trial

BackgroundThree techniques of magnetic resonance imaging (MRI)-based targeted biopsy (TB) of the prostate exist. There is no superiority regarding diagnostic efficacy of prostate cancer (PCa) detection. ObjectiveTo compare adverse events (AEs) among three TB techniques and to evaluate the effect on urinary and erectile function. Design, setting, and participantsPost hoc analysis of a multicentre randomised controlled trial among men with negative systematic biopsy (SB) and suspicion of PCa. InterventionIn 234 patients, 3-T multiparametric MRI demonstrated PIRADS≥ 3 lesions, and patients were randomised 1:1:1 for TB: transrectal in-bore MRI TB (MRI-TB), transperineal MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), and transrectal cognitive TRUS TB (COG-TB). Outcome measurements and statistical analysisAEs (Clavien-Dindo) were compared using Pearson chi-square test. Univariate logistic regression tests were performed for the number of cores, biopsy approach, and usage of anticoagulants. The participants filled in baseline and 30-d postbiopsy International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires. The delta between measurements was compared using one-way analysis of variance. Results and limitationsThere were significant differences in minor AEs: 53% in MRI-TB, 71% in FUS-TB, and 85% in COG-TB (p < 0.001). The number of cores was associated with AEs (odds ratio [OR] 1.11 per extra biopsy [95% confidence interval {CI} 1.06–1.17, p < 0.001]). Anticoagulants were not associated with bleeding complications (OR 1.24 [95% CI 0.66–2.35, p = 0.5]). Transrectal approach (MRI-TB + COG-TB) increased the risk of any AE (OR 2.54 [95% CI 1.16–5.77, p < 0.05]) and nonsignificantly increased the risk of urinary tract infections (OR 3.69 [95% CI 0.46–168.4, p = 0.3]). Biopsy did not impact urinary (ΔIPSS 0.3, p = 0.1) and erectile function (ΔIIEF-5 –0.4, p = 0.5). The main limitation was that additional SB was performed in FUS-TB and COG-TB, and was omitted in MRI-TB, making comparison difficult. ConclusionsThere was a significant difference in minor AEs among groups. An increase in the number of cores increased the overall risk of AEs. A low AE occurrence in MRI-TB was likely caused by the omission of SB. Prostate biopsy did not impact self-reported urinary and erectile functions. Patient summaryIn this study, we compared the complication rates of three techniques of magnetic resonance imaging (MRI)-based targeted biopsy of the prostate. We found a significant difference in the occurrence of minor complication rates among three groups in favour of transrectal in-bore MRI targeted biopsy, likely caused by the omission of additional systematic biopsy in this group.

Rates of Adverse Outcomes and Revision Surgery After Anterior Cruciate Ligament Reconstruction: A Study of 104,255 Procedures Using the National Hospital Episode Statistics Database for England, UK

Background: After an anterior cruciate ligament (ACL) injury, ACL reconstruction is an elective procedure, and therefore, an understanding of the attributable risk from undergoing ACL reconstruction is necessary for patients to make a fully informed treatment decision. Purpose: To determine the absolute risk of adverse outcomes including reoperation after ACL reconstruction with comparison, where possible, to the rate of adverse events reported in the general population. Study Design: Descriptive epidemiology study. Methods: National hospital data on all ACL reconstructions performed in England between April 1, 1997, and March 31, 2017, were analyzed. Revision cases, bilateral procedures within 6 months, and cases with concurrent cartilage or multiple ligament surgery were excluded. The primary outcome was the occurrence of at least 1 serious complication (myocardial infarction, stroke, pulmonary embolism, infection requiring surgery, fasciotomy, neurovascular injury, or death) within 90 days. Additionally, 5-year rates of revision ACL reconstruction, contralateral ACL reconstruction, and meniscal surgery were investigated. Results: There were 133,270 ACL reconstructions performed, of which 104,255 were eligible for analysis. Within 90 days, serious complications occurred in 675 (0.65% [95% CI, 0.60-0.70]), including 494 reoperations for infections (0.47% [95% CI, 0.43-0.52]) and 129 for pulmonary embolism (0.12% [95% CI, 0.10-0.15]). Of 54,275 procedures with at least 5 years’ follow-up, 1746 (3.22% [95% CI, 3.07-3.37]) underwent revision ACL reconstruction in the same knee, 1553 underwent contralateral ACL reconstruction (2.86% [95% CI, 2.72-3.01]), and 340 underwent meniscal surgery (0.63% [95% CI, 0.56-0.70]). The overall risk of serious complications fell over time (adjusted odds ratio [OR], 0.96 per year [95% CI, 0.95-0.98]); however, older patients (adjusted OR, 1.11 per 5 years [95% CI, 1.07-1.16]) and patients with a greater modified Charlson Comorbidity Index (adjusted OR, 2.41 per 10 units [95% CI, 1.65-3.51]) were at a higher risk. For every 850 (95% CI, 720-1039) ACL reconstructions, 1 pulmonary embolism could be provoked. For every 213 (95% CI, 195-233), 1 native knee joint infection could be provoked. Conclusion: The overall risk of adverse events after ACL reconstruction is low; however, some rare but serious complications, including infections or pulmonary embolism, may occur. Around 3% of patients undergo further ipsilateral or contralateral ACL reconstruction within 5 years. These data will inform shared decision making between clinicians and patients considering their treatment options.

Adverse events of benralizumab in moderate to severe eosinophilic asthma: A meta-analysis.

Benralizumab, a humanized, anti-interleukin-5 (anti-IL-5) receptor α monoclonal antibody that directly and rapidly depletes eosinophils, has shown significant efficacy in reducing asthma exacerbations and improving lung function in moderate to severe eosinophilic asthma patients. However, there is some controversy regarding the adverse events (AEs) of benralizumab and a comprehensive analysis of these AEs has not been performed. This study aimed to assess the incidence of these AEs in published randomized controlled trials (RCTs). We searched for RCTs in the Embase, PubMed and Cochrane databases that compared benralizumab with placebo in moderate to severe eosinophilic asthma patients. The outcome was the incidence of AEs during the observation period. Eight RCTs were analyzed in this study. Patients treated with benralizumab had a lower risk of overall AEs (risk ratio (RR) 0.94; 95% confidence interval (CI) 0.90-0.98), serious adverse events (SAEs) (RR 0.82; 95% CI 0.68-0.98), asthma exacerbation (RR 0.72, 95% CI 0.61-0.85), bronchitis (RR 0.76, 95% CI 0.59-0.96) and sinusitis (RR 0.64, 95% CI 0.48-0.85), but had a higher risk of headache (RR 1.42, 95% CI 1.07-1.87) and pyrexia (RR 2.26, 95% CI 1.32-3.87) than patients treated with placebo. No increased incidence of death, hypersensitivity, injection-site reactions, nasopharyngitis, rhinitis, upper respiratory tract infection, influenza, cough, nausea, back pain or arthralgia was observed with benralizumab compared with placebo. Benralizumab reduced the risk of SAEs, asthma exacerbation, bronchitis and sinusitis, and aggravated the risk of headache and pyrexia. Other AEs were comparable between the benralizumab group and placebo group. Therefore, benralizumab is a relatively safe drug, but vigilance regarding AEs is imperative during long-term treatment.

Safety and efficacy of hot avulsion as an adjunct to EMR (with videos)

Excision of all visible neoplastic tissue is the goal of EMR of colorectal laterally spreading tumors. Flat and fibrotic tissue can resist snaring. Ablation of visible polyps is associated with high recurrence rates. Avulsion is a technique to continue resection when snaring fails. We retrospectively analyzed colonic EMRs of 564 consecutive referred polyps between 2015 and 2017. Hot avulsion was used when snaring was unsuccessful. Polyps treated with and without avulsion were compared. Hot avulsion was used in 20.9% (n= 112) of all resected lesions. The recurrence rates on follow-up colonoscopy were 17.52% in the avulsion group versus 16.02% in the non-avulsion group (P= .76). Hot avulsion was associated with a trend toward higher rates of delayed hemorrhage (5.35% vs 2.58%; P= .15) and post-coagulation syndrome (1.8% vs 0.47%; P= .15), but polyps treated with any avulsion were larger than those in which no avulsion was used (P< .001). There were an insufficient number of adverse events to perform a multivariable analysis to test the effects of avulsion, size, and location on the risk of overall adverse events. Unlike previous reports of using argon plasma coagulation to treat visible polyps during EMR, hotavulsion of visible/fibrotic neoplasia was associated with similar EMR efficacy compared with cases that did not require hot avulsion. The safety profile of hot avulsion appears acceptable.

Safety and efficacy of apatinib in elderly patients with advanced or metastatic gastric cancer in the post-marketing phase IV study: Subgroup analysis by age (Ahead-G201).

126 Background: Old age is a potential negative predictor, and thus is of interest. Data from the ongoing post-marketing Phase IV trial were collected to assess the effect of age on apatinib treatment in 2000+ patients (pts) with chemotherapy-refractory advanced or metastatic gastric cancer. Methods: This subgroup analysis was stratified by age (&lt;65 or ≥65 yrs). Both incidence of adverse events (AEs) and clinical outcomes were compared. Results: 725 pts &lt;65 yrs and 312 pts ≥65 yrs were enrolled (data cut-off 2017/7/10). Differences in gender, ECOG PS, BMI, disease duration and metastatic sites were observed. 68.6% and 39.7% of pts aged ≥65 yrs experienced AEs of any grade and grade ≥3, which were not different with 70.2% and 40.0% of pts aged &lt;65 yrs. The common AE profile was similar, but elderly pts had a higher incidence of hypertension, diarrhea and bilirubin increase (Table). Pts ≥65 yrs showed a higher objective response rate (12.2% vs. 9.9%) and longer overall survival (7.82 vs. 6.05 mos); however, there was no statistical difference. The disease control rate (79.6% vs. 65.4%; p=0.002) and progression free survival (PFS) (5.71 vs. 3.22 mos; p&lt;0.001) of pts ≥65 yrs were significantly superior to pts &lt;65 yrs. Multivariate Cox regression model confirmed that age ≥65 yr was a positive prognostic factor for PFS independent of baseline and treatment characteristics (HR: 0.67 [95%CI, 0.50–0.88]). Conclusions: Pts ≥65 yr is not at increased risk of overall AEs, but hypertension, diarrhea and bilirubin increase should be closely monitored. The PFS benefit in elderly pts will be validated. Clinical trial information: NCT02426034. [Table: see text]

Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials.

Topical growth factors accelerate wound healing in patients with diabetic foot ulcers (DFU). Due to the absence of head-to-head comparisons, we carried out Bayesian network meta-analysis to compare the efficacy and safety of growth factors. Using an appropriate search strategy, randomized controlled trials on topical growth factors compared with standard of care in patients with DFU, were included. Proportion of patients with complete healing was the primary outcome. Odds ratio (95% confidence interval) was used as the effect estimate and random effects model was used for both direct and indirect comparisons. Markov Chain Monte Carlo simulation was used to obtain pooled estimates. Rankogram was generated based on surface under the cumulative ranking curve (SUCRA). A total of 26 studies with 2088 participants and 1018 events were included. The pooled estimates for recombinant epidermal growth factor (rhEGF), autologous platelet rich plasma (PRP), recombinant human platelet-derived growth factor (rhPDGF) were 5.72 [3.34, 10.37], 2.65 [1.60, 4.54] and 1.97 [1.54, 2.55] respectively. SUCRA for rhEGF was 0.95. Sensitivity analyses did not reveal significant changes from the pooled estimates and rankogram. No differences were observed in the overall risk of adverse events between the growth factors. However, the growth factors were observed to lower the risk of lower limb amputation compared to standard of care. To conclude, rhEGF, rhPDGF and autologous PRP significantly improved the healing rate when used as adjuvants to standard of care, of which rhEGF may perform better than other growth factors. The strength of most of the outcomes assessed was low and the findings may not be applicable for DFU with infection or osteomyelitis. The findings of this study needs to be considered with caution as the results might change with findings from head-to-head studies.

New approach to decrease post-ERCP adverse events in patients with primary sclerosing cholangitis.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) is often performed in patients with primary sclerosing cholangitis (PSC). Our aim was to validate a treatment approach with the objective of decreasing ERCP related adverse events (AEs). Patients and methods All patients who had undergone ERCP for PSC during the period from 2002 – 2012 were identified (group I). This group had traditional ERCP (no bile aspiration prior to contrast injection with balloon dilation and stent placement for treatment of dominant strictures). To decrease ERCP-related AEs, we changed the ERCP approach in which bile aspiration was performed prior to contrast injection and balloon dilation alone was performed for treatment of dominant strictures. This was tested prospectively in all patients undergoing ERCP for PSC from 2012 – 2014 (group II). Results The risk of overall AEs and cholangitis was relatively less in group II compared with group I [(2.1 % vs. 10.3 %; P = .38) and (0 % vs. 4.4 %; P = .68)]. On bivariate analysis, change in ERCP approach was associated with decreased risk of post-procedure cholangitis (0 % vs. 10.2 %, P = .03) and overall AE (0 % vs. 18.6 %, P = .03). There were no AEs in 22/46 patients in group II who had bile aspiration with balloon dilation. On multivariate analysis, only biliary stent placement was associated with increased risk of AEs (OR 4.10 (1.32 – 12.71); P = .02) and cholangitis (OR 5.43, 1.38 – 21.38; P = .02) respectively. Conclusion Biliary aspiration and avoidance of stenting approach after dilation of strictures during ERCP in PSC patients appears to be associated with decreased risk of cholangitis and overall AEs. Future prospective randomized controlled trials are needed to validate our observation.

Carbon Dioxide versus Air Insufflation in Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background/AimsEndoscopic submucosal dissection (ESD) with air insufflation is commonly used for the staging and treatment of early gastric carcinoma. However, carbon dioxide (CO2) use has been shown to cause less post-procedural pain and fewer adverse events. The objective of this study was to compare the post-procedural pain and adverse events associated with CO2 and air insufflation in ESD.MethodsA systematic search was conducted for randomized control trials (RCTs) comparing the two approaches in ESD. The Mantel-Haenszel method was used to analyze the data. The mean difference (MD) and odds ratio (OR) were used for continuous and categorical variables, respectively.ResultsFour RCTs with a total of 391 patients who underwent ESD were included in our meta-analysis. The difference in maximal post-procedural pain between the two groups was statistically significant (MD, -7.41; 95% confidence interval [CI], -13.6 – -1.21; p=0.020). However, no significant differences were found in the length of procedure, end-tidal CO2, rate of perforation, and postprocedural hemorrhage between the two groups. The incidence of overall adverse events was significantly lower in the CO2 group (OR, 0.51; CI, 0.32–0.84; p=0.007).Conclusions:CO2 insufflation in gastric ESD is associated with less post-operative pain and discomfort, and a lower risk of overall adverse events compared with air insufflation.

Non-contraceptive oestrogen-containing preparations for controlling symptoms of premenstrual syndrome.

Non-contraceptive oestrogen-containing preparations for controlling symptoms of premenstrual syndrome.

Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

Given inconsistent trial results of sodium-glucose cotransporter 2 (SGLT2) inhibitors in addition to insulin therapy for treating type 2 diabetes mellitus (T2DM), a meta-analysis was performed to evaluate the efficacy and safety of this combination for T2DM by searching available randomized trials from PubMed, Embase, CENTRAL and ClinicalTrials.gov. Our meta-analysis included seven eligible placebo-controlled trials involving 4235 patients. Compared with placebo, SGLT2 inhibitor treatment was significantly associated with a mean reduction in HbA1c of -0.56%, fasting plasma glucose of -0.95 mmol/L, body weight of -2.63 kg and insulin dose of -8.79 IU, but an increased risk of drug-related adverse events by 36%, urinary tract infections by 29% and genital infections by 357%. No significant increase was observed in risk of overall adverse events [risk ratio (RR), 1.00], serious adverse events (RR, 0.90), adverse events leading to discontinuation (RR, 1.16), hypoglycaemia events (RR, 1.07) and severe hypoglycaemia events (RR, 1.24). No diabetic ketoacidosis events were reported. Further studies are needed to establish optimal combination type and dose.