Total Number Of Adverse Events Research Articles

A Combination of Peppermint Oil and Caraway Oil for the Treatment of Functional Dyspepsia: A Systematic Review and Meta-Analysis.

A combination of peppermint oil and caraway oil (POCO) with its unique properties has been shown clinical benefits for FD. However, the potent statistical data to confirm its effects are lacking. This meta-analysis thus aimed at evaluating the efficacy and safety of POCO compared with placebo in treating patients with FD. We searched CENTRAL, PubMed, EMBASE (Ovid), Web of Science, Google Scholar, China National Knowledge Infrastructure database, Wanfang, and VIP databases for randomized clinical trials (RCTs) up to June 2019. Dichotomous data were shown as a risk ratio (RR) with 95% confidence intervals (CIs). All data were analyzed by Review Manager 5.2 software. The search identified 382 citations, and 5 RCTs (578 participants) were included. POCO showed a statistically significant effect in global improvement of FD symptoms (RR for not much or very much improvement 0.59, 95% CI: 0.49 to 0.71, P < 0.00001, I2 36%, NNT 3) and improvement in epigastric pain (RR 1.61, 95% CI: 1.28 to 2.03, P < 0.0001, I2 0%, NNT 3). There were no significant differences in the total number of adverse events between POCO and placebo (NNH 40). In conclusion, this is the first meta-analysis to assess the effects of POCO in FD. POCO is an effective and safe short-term treatment for FD. However, current findings are based on smaller sample sizes and low/very low quality of the evidence. More well-designed RCTs with large sample sizes of FD patients are required.

Incidence of Intraoperative and Early Postoperative Adverse Events in a Large Cohort of Consecutive Laser Vision Correction Treatments

To evaluate the incidence of adverse events (AE) following laser vision correction. Retrospective case series. Optical Express, UK. Patients/study population: patients who underwent laser insitu keratomileusis (LASIK) or photorefractive keratectomy (PRK) between July 1, 2014, and June 30, 2016. Intervention/observation procedures: all AEs recorded in the electronic medical record were extracted and retrospectively reviewed. The total incidence of AE and serious adverse events (SAE) was calculated. Loss of 2 or more lines of corrected distance visual acuity (CDVA) was calculated for the entire cohort of patients that attended a minimum of 3months follow-up. AEs; Preoperative and last available postoperative clinical data. A total of 31,921 (61,833 eyes) were included in the study for LASIK and 5,016 (9,467 eyes) for PRK. The total number of AE was 850 for LASIK (occurring in 783 eyes of 657 patients; incidence of 1.3% or 1:79 eyes) and 227 for PRK (occurring in 218 eyes of 170 patients; incidence of 2.3% or 1:43 eyes). In the LASIK group, there were 287 SAEs (271 eyes of 226 patients; incidence of 0.4% or 1:228 eyes), and the number of SAEs in PRK group was 65 (65 eyes of 39 patients; incidence 0.7% or 1:146 eyes). Combining LASIK and PRK data, the loss of 2 or more lines of CDVA was recorded in 0.37% of eyes. Contemporary LASIK and PRK are safe procedures with a low incidence of serious adverse events.

What Is the Return on Investment for Implementation of a Crew Resource Management Program at an Academic Medical Center?

Crew Resource Management (CRM) training has been used successfully within hospital units to improve quality and safety. This article presents a description of a health system-wide implementation of CRM focusing on the return on investment (ROI). The costs included training, programmatic fixed costs, time away from work, and leadership time. Cost savings were calculated based on the reduction in avoidable adverse events and cost estimates from the literature. Between July 2010 and July 2013, roughly 3000 health system employees across 12 areas were trained, costing $3.6 million. The total number of adverse events avoided was 735-a 25.7% reduction in observed relative to expected events. Savings ranged from a conservative estimate of $12.6 million to as much as $28.0 million. Therefore, the overall ROI for CRM training was in the range of $9.1 to $24.4 million. CRM presents a financially viable way to systematically organize for quality improvement.

Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis

There are several drugs available for the treatment of chronic idiopathic constipation, but their relative efficacy is unclear because there have been no head-to-head randomised controlled trials. We did a network meta-analysis to compare the efficacy of these therapies in patients with chronic idiopathic constipation. We searched Medline, Embase, Embase Classic, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published from inception to week 3 June, 2019, to identify randomised controlled trials assessing the efficacy of drugs (osmotic or stimulant laxatives, elobixibat, linaclotide, lubiprostone, mizagliflozin, naronapride, plecanatide, prucalopride, tegaserod, tenapanor, or velusetrag) in adults with chronic idiopathic constipation. Participants had to be treated for a minimum of 4 weeks, and we extracted data for all endpoints preferentially at 4 weeks, 12 weeks, or both. Trials included in the analysis reported a dichotomous assessment of overall response to therapy (response or no response to therapy). We pooled the data using a random effects model, and reported efficacy and safety of all treatments as a pooled relative risk (RR) with 95% CIs to summarise the effect of each comparison tested. To rank treatments, we used P-scores, which measure the extent of certainty that a treatment is better than another treatment, averaged over all competing treatments. We identified 33 eligible randomised controlled trials of drugs, comprising 17 214 patients. Based on an endpoint of failure to achieve three or more complete spontaneous bowel movements (CSBMs) per week, the stimulant diphenyl methane laxatives bisacodyl and sodium picosulfate, at a dose of 10 mg once daily, were ranked first at 4 weeks (RR 0·55, 95% CI 0·48-0·63, P-score 0·99), and prucalopride 2 mg once daily ranked first at 12 weeks (0·82, 0·78-0·86, P-score 0·96). When response to therapy was defined as falilure to achieve an increase of one or more CSBM per week from baseline, diphenyl methane laxatives at a dose of 10 mg once daily ranked first at 4 weeks (0·44, 0·37-0·54, P-score 0·99), with prucalopride 4 mg once daily ranked first at 12 weeks (0·74, 0·66-0·83, P-score 0·79), although linaclotide 290 μg once daily and prucalopride 2 mg once daily had similar efficacy (P-scores of 0·76 and 0·71, respectively). Bisacodyl ranked last in terms of safety for total number of adverse events and abdominal pain (P-score 0·08). Almost all drugs studied were superior to placebo, according to either failure to achieve three or more CSBMs per week or or failure to achieve an increase of one or more CSBM per week over baseline. Although diphenyl methane laxatives ranked first at 4 weeks, patients with milder symptoms might have been included in these trials. Prucalopride ranked first at 12 weeks, and many of the included trials recruited patients who previously did not respond to laxatives, suggesting that this drug is likely to be the most efficacious for patients with chronic idiopathic constipation. However, because treatment duration in most trials was 4-12 weeks, the long-term relative efficacy of these drugs is unknown. None.

Efficacy and safety of desmopressin in women with nocturia: a systematic review and meta-analysis of randomized controlled trials.

To evaluate the efficacy and safety of desmopressin treatment in women with nocturia. The PubMed, EMBASE, ISI web of knowledge, and the Cochrane Controlled Trial Register of Controlled Trials were searched from their inception date till April, 2019. The meta-analysis was performed by Revman 5.3. This review also stratified each outcome by dose (< 25μg, 25μg versus > 25μg) to explore the differences in the dose response for orally disintegrating tablet (ODT). Seven publications with seven trials were included in this review. The methodological quality of these trials was fair, and four studies had low risk of bias. The number of nocturnal voids per night was significantly decreased by desmopressin when compared to the control [6 trials, Weighted Mean Difference(WMD) = 0.41, P < 0.00001], and the difference between < 25, 25 and > 25μg dose ODT groups was also significant (P = 0.03). The duration of first sleep period was significantly increased by desmopressin [4 trials, WMD = 66.64, P < 0.00001], and the difference between these three doses ODT was not significant (P = 0.15). Overall, the risk ratios (RR) for 33% responder rate showed significance when compared with desmopressin to controls [3 trials, RR = 1.30, P = 0.0003]. The number of total adverse events was similar in both desmopressin and control groups [5 trials, RR = 0.95, P = 0.59], otherwise, showed no significant difference between different ODT dose groups (P = 0.82). Desmopressin had certain efficacy and adequate safety in women with nocturia. The exploration of appropriate dose for female patients, and other influential factors, such as age should be conducted and considered in future.

Smoking status and perioperative adverse events in patients undergoing cranial tumor surgery.

Smoking is agreed to be a major health risk factor, but it is debated whether it has an influence on perioperative adverse events (AEs) in elective cranial tumor surgery. We analyzed the 2013-2016 data from our prospective institutional patient registry. Consecutive patients undergoing elective microsurgical tumor surgery of a glioma or a meningioma were included. Patients were categorized as active smokers, former smokers, and non-smokers. AE were graded by the therapy-oriented Clavien-Dindo scale. Possible predictors of postoperative AE were identified with the help of a binomial logistic regression model. We identified 798 patients, out of which 480 were non-smokers, 193 active smokers, and 125 former smokers. The rate of AEs for active smokers (30%, 95% CI [23-37%]) was indistinguishable from the AE rate of non-smokers (32%, 95% CI [28-37%]). No difference between smoking status was found looking at all AE individually, the odds ratio of suffering from local AE and systemic AE respectively were the same between all smoking groups. The modified Rankin scale at hospital admission was a strong and significant predictor of postoperative AE (P = 0.013). Active smoking was not associated with an increased risk for postoperative AE, neither looking at the total number of AE nor looking at individual AE. Smoking status should therefore not be a major factor in preoperative decision making. Although not based on data of this study, doctors should always encourage patients to stop smoking due to its well-known detrimental health effect.

PMU39 APPROACHES TO SAFETY REPORTING IN OBSERVATIONAL STUDIES

Regulatory agencies, like the Food and Drug Administration or European Medicines Agency, may request post-marketing studies to assess new safety information in order to estimate the risks or serious risks related to a drug1. Although these agencies provide guidance, a standard model of how to present reported adverse events (AEs) proved difficult to find. Our objective is to examine variations among presentations of safety reporting in observational studies. We gathered different representations of safety tables that have been submitted to regulatory agencies by other entities. Cross-comparisons of the reports were done to inform how safety data is to be displayed in terms of layout and content. Safety tables can include one or multiple MedDRA coding categories: system organ class, high-level group term, preferred term, high-level term, and lower-level term, which may be stratified by the overall cohort, sub-cohorts, or by AE severity/grade. Additional information, such as “Total patients with at least one AE,” “Total Number of AEs,” and “Count of Unique AEs,” provide an brief summary of the AEs to the reader. There are also numerous subsets that include but are not limited to: all treatment-emergent AEs, serious AEs, treatment-related AEs, commonly reported AEs (preferred terms >10%), or AEs of special interest. In conclusion, safety reporting can differ depending upon regulatory agency specifications. Understanding the different approaches can help vendors anticipate requests and/or make recommendations.

Adverse events within 1 year after surgical and percutaneous closure of atrial septal defects in preterm children.

Atrial septal defect is the third most common CHD. A hemodynamically significant atrial septal defect causes volume overload of the right side of the heart. Preterm children may suffer from both pulmonary and cardiac comorbidities, including altered myocardial function. The aim of this study was to compare the rate of adverse events following atrial septal defect closure in preterm- and term-born children. We performed a retrospective cohort study including children born in Sweden, who had a surgical or percutaneous atrial septal defect closure at the children's hospitals in Lund and Stockholm, between 2000 and 2014, assessing time to the first event within 1 month or 1 year. We analysed differences in the number of and the time to events between the preterm and term cohort using the Kaplan-Meier survival curve, a generalised model applying zero-inflated Poisson distribution and Gary-Anderson's method. Overall, 413 children were included in the study. Of these, 93 (22.5%) were born prematurely. The total number of adverse events was 178 (110 minor and 68 major). There was no difference between the cohorts in the number of events, whether within 1 month or within a year, between major (p = 0.69) and minor (p = 0.84) events or frequencies of multiple events (p = 0.92). Despite earlier procedural age, larger atrial septal defects, and higher comorbidity than term children, preterm children appear to have comparable risk for complications during the first year after surgical or percutaneous closure.

Efficacy of pharmacological therapies in patients with IBS with diarrhoea or mixed stool pattern: systematic review and network meta-analysis

ObjectiveOver half of patients with IBS have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licenced pharmacological therapies is unclear in the absence of head-to-head...

Pharmacist-Managed Inpatient Dofetilide Initiation Program: Description and Adherence Rate Post-Root Cause Analysis

The aim of this article is to describe the pharmacist-managed dofetilide initiation program at Maine Medical Center (MMC), assess the adherence rate to 8 core clinical metrics, and review adverse effects before and after a root cause analysis (RCA). Core clinical metrics included pharmacist note entered within 4 hours of dose administration, dose chosen correctly per renal function, QTc measurements obtained and reviewed 2 hours after each dose, appropriate dose adjustment per the most recent QTc measurement, documentation of patient education, and assessment of conduction abnormality, drug–drug interactions, and serum potassium and magnesium concentrations. The primary outcome was adherence rate to all 8 core clinical metrics before and after the RCA. The safety outcome was the total number of adverse events. One hundred patients undergoing elective dofetilide initiation were evaluated: 50 pre-RCA and 50 post-RCA. Adherence rate to all core metrics was 14% in the pre-RCA group and 44% in the post-RCA group (P < .001). Torsade de pointes occurred 3 times in the pre-RCA group and never in the post-RCA group. After the RCA, adherence to MMC’s pharmacist-managed inpatient dofetilide initiation program significantly improved.

Randomized trial of add-on triheptanoin vs medium chain triglycerides in adults with refractory epilepsy.

SummaryObjectiveTo investigate the feasibility, safety, and tolerability of add‐on treatment of the triglycerides of heptanoate (triheptanoin) vs the triglycerides of octanoate and decanoate (medium chain triglycerides [MCTs]) in adults with treatment‐refractory epilepsy.MethodsAfter an 8‐week prospective baseline period, people with drug‐resistant epilepsy were randomized in a double‐blind fashion to receive triheptanoin or MCTs. Treatment was titrated over 3 weeks to a maximum of 100 mL/d to be distributed over 3 meals and mixed into food, followed by 12‐week maintenance before tapering. The primary aims were to assess the following: (a) safety by comparing the number of intervention‐related adverse events with triheptanoin vs MCT treatment and (b) adherence, measured as a percentage of the prescribed treatment doses taken.ResultsThirty‐four people were randomized (17 to MCT and 17 to triheptanoin). There were no differences regarding (a) the number of participants completing the study (11 vs 9 participants), (b) the time until withdrawal, (c) the total number of adverse events or those potentially related to treatment, (d) median doses of oils taken (59 vs 55 mL/d, P = 0.59), or (e) change in seizure frequency (54% vs 102%, P = 0.13). Please note that people with focal unaware seizures were underrepresented in the triheptanoin treatment arm (P = 0.04). The most common adverse events were gastrointestinal disturbances (47% and 62.5% of participants). Five people taking on average 0.73 mL/kg body weight MCTs (0.64 mL/kg median) and one person taking 0.59 mL/kg triheptanoin showed >50% reduction in seizure frequency, specifically focal unaware seizures.SignificanceAdd‐on treatment with MCTs or triheptanoin was feasible, safe, and tolerated for 12 weeks in two‐thirds of people with treatment‐resistant epilepsy. Our results indicate a protective effect of MCTs on focal unaware seizures. This warrants further study.

Immunonutrition for acute respiratory distress syndrome (ARDS) in adults.

Acute respiratory distress syndrome (ARDS) is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Pharmacotherapies that moderate inflammation in ARDS are lacking. Several trials have evaluated the effects of pharmaconutrients, given as part of a feeding formula or as a nutritional supplement, on clinical outcomes in critical illness and ARDS. To systematically review and critically appraise available evidence on the effects of immunonutrition compared to standard non-immunonutrition formula feeding on mechanically ventilated adults (aged 18 years or older) with acute respiratory distress syndrome (ARDS). We searched MEDLINE, Embase, CENTRAL, conference proceedings, and trial registries for appropriate studies up to 25 April 2018. We checked the references from published studies and reviews on this topic for potentially eligible studies. We included all randomized controlled trials (RCTs) and quasi-randomized controlled trials comparing immunonutrition versus a control or placebo nutritional formula in adults (aged 18 years or older) with ARDS, as defined by the Berlin definition of ARDS or, for older studies, by the American-European Consensus Criteria for both ARDS and acute lung injury. Two review authors independently assessed the quality of studies and extracted data from the included trials. We sought additional information from study authors. We performed statistical analysis according to Cochrane methodological standards. Our primary outcome was all-cause mortality. Secondary outcomes included intensive care unit (ICU) length of stay, ventilator days, indices of oxygenation, cardiac adverse events, gastrointestinal adverse events, and total number of adverse events. We used GRADE to assess the quality of evidence for each outcome. We identified 10 randomized controlled trials with 1015 participants. All studies compared an enteral formula or additional supplemental omega-3 fatty acids (i.e. eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)), gamma-linolenic acid (GLA), and antioxidants. We assessed some of the included studies as having high risk of bias due to methodological shortcomings. Studies were heterogenous in nature and varied in several ways, including type and duration of interventions given, calorific targets, and reported outcomes. All studies reported mortality. For the primary outcome, study authors reported no differences in all-cause mortality (longest period reported) with the use of an immunonutrition enteral formula or additional supplements of omega-3 fatty acids and antioxidants (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07; participants = 1015; studies = 10; low-quality evidence).For secondary outcomes, we are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants reduces ICU length of stay (mean difference (MD) -3.09 days. 95% CI -5.19 to -0.99; participants = 639; studies = 8; very low-quality evidence) and ventilator days (MD -2.24 days, 95% CI -3.77 to -0.71; participants = 581; studies = 7; very low-quality evidence). We are also uncertain whether omega-3 fatty acids and antioxidants improve oxygenation, defined as ratio of partial pressure of arterial oxygen (PaO₂) to fraction of inspired oxygen (FiO₂), at day 4 (MD 39 mmHg, 95% CI 10.75 to 67.02; participants = 676; studies = 8), or whether they increase adverse events such as cardiac events (RR 0.87, 95% CI 0.09 to 8.46; participants = 339; studies = 3; very low-quality evidence), gastrointestinal events (RR 1.11, 95% CI 0.71 to 1.75; participants = 427; studies = 4; very low-quality evidence), or total adverse events (RR 0.91, 95% CI 0.67 to 1.23; participants = 517; studies = 5; very low-quality evidence). This meta-analysis of 10 studies of varying quality examined effects of omega-3 fatty acids and/or antioxidants in adults with ARDS. This intervention may produce little or no difference in all-cause mortality between groups. We are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves the duration of ventilator days and ICU length of stay or oxygenation at day 4 due to the very low quality of evidence. Adverse events associated with immunonutrition are also uncertain, as confidence intervals include the potential for increased cardiac, gastrointestinal, and total adverse events.

Glimepiride as Add-on Therapy in Type 2 Diabetic Patients with Metformin Monotherapy: A Real-Life Study from Egypt

AbstractBackground: Adding glimepiride to metformin mono-therapy was reported to improve the glycemic status of patients with type 2 diabetes mellitus (T2DM), with tolerable safety profile.Aim of Work: The present real-life study aimed to inves-tigate the safety and effectiveness of glimepiride add-on therapy in poorly controlled T2DM patients with metformin monotherapy.Patients and Methods: In the present prospective study, we included 1050 poorly controlled T2DM patients from Egypt, and for whom the investigators decided to prescribe glimepiride in addition to metformin. Glimepiride was added to patients uncontrolled on metformin monotherapy for at least three months despite reaching the maximally tolerated dose. Regimen doses were decided by the investigators to reflect the in-practice approach. We followed the included patients for at three months and safety outcomes were measured throughout the study period.Results: After three months of treatment, the mean HbA1c level decreased by 1.54% (95% CI: –1.61 to –1.46%), with a mean percentage reduction of 16.3% (p<0.001). In addition, 31.7% of the included patients achieved the targeted HbA1c level <7%. The total number of adverse events was 15 adverse events occurred in 11 patients. Ten episodes of non-serious hypoglycemia were recorded.Conclusion: The present real-life study confirms the efficacy of glimepiride add-on therapy to metformin mono-therapy among poorly controlled T2DM patients from Egypt. Moreover, glimepiride/metformin regimen exhibits well-tolerable safety profile.

Comparison of Outcomes between the Cellex and Uvar-Xts Closed-System Extracorporeal Photopheresis (ECP) Devices When Used for Graft-Versus-Host Disease; A Single Center Experience

Abstract BACKGROUND: Graft versus host disease (GVHD) is a significant contributor to non-relapse mortality after allogeneic stem cell transplant (SCT). Steroids are first line therapy and extracorporeal photopheresis (ECP) is used as second line therapy for steroid refractory or intolerant patients. ECP has immunomodulatory effects rather than immunosuppressive effect which decreases the risk of infection, and may decreases the risk of disease relapse. There are two ECP instruments approved in the US for the treatment of Cutaneous T Cell Lymphoma (CTLC), however both have been used "off-label" to prevent or treat solid organ transplant rejection, acute and chronic GVHD, and other autoimmune diseases. Until recently the UVAR-XTS instrument has been the most commonly used closed system in the US until the CELLEX was approved in 2009. The CELLEX and the UVAR-XTS procedures are similar in that buffy coat is collected, exposed to methoxsalen (UVADEX®) ex vivo and then UVA light before returning the treated cells back to the patient in a closed looped system. The instruments differ in the collection of the buffy coat; collection is continuous by the CELLEX, and it is intermittent by UVAR-XTS. In addition CELLEX has been shown to be more efficient in collecting mononuclear cells when compared to the UVAR -XTS. Little clinical data is available comparing the clinical efficacy of the two instruments in the setting of GVHD. We designed a single institution retrospective study to compare the efficacy and safety of the two instruments. The primary outcomes analyzed were &gt;/=50% reduction of steroid dose between the initial and final dose during the study period, and the number and type of adverse events that occurred during the ECP procedures. METHODS: Study Population: We reviewed charts of allogeneic stem cell transplant patients who received ECP for the treatment of acute or chronic GVHD between 1/2009 and 12/2015. The patients were divided into two groups based on the type of ECP instrument that was used. One group was exclusively treated with UVAR-XTS while the second group with CELLEX. Patients who received treatments with both instruments were excluded. The frequency of steroid dose reduction by &gt;/=50%, and toxicity was compared between the two instruments while adjusting for age, gender, GVHD severity, number of organs involved by GVHD, type of allogeneic stem cell transplant, conditioning regimen, number of other immunosuppressants, type of anticoagulants (ACDA vs heparin), type of access line, and baseline blood counts. Statistical Analysis: The baseline characteristics of the patients in the two groups were compared using Chi square, Fischer's exact test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. Chi square analysis was used to determine the difference in frequency of &gt;/=50% steroid dose reduction and adverse events between the two groups. Logistic multivariate regression was used to evaluate the potential interactions of all significant covariates. A p value of less than 0.05 was considered to be statistically significant. Statistical analyses were performed using STATA14 software (StataCorp, College Station, TX). RESULTS: We identified 242 allogeneic SCT recipients who received ECP for acute or chronic GVHD in the study period, 146 of whom met the selection criteria. 69 patients had all procedure performed with UVAR-XTS and 77 patients had all procedures performed with CELLEX. There was no significant difference in age, gender, percent of acute GVHD, anticoagulant used, type of transplant, number of organs involved, number of immunosuppressants, vascular access and baseline blood counts between the two treatment cohorts as shown in table 1. Although year of transplant and conditioning regimen were different between the two cohorts, neither of these covariates influenced the impact of instrument on the primary outcome. In multivariate analysis, the patients who underwent ECP with CELLEX were 3 times more likely to have &gt;/=50% steroid dose reduction (p =0.01). The total number of adverse events was similar between the instruments (p = 0.73). (Table 2) CONCLUSION: More than twice as many patients with GVHD treated with the CELLEX had a steroid dose reduction by &gt;/=50% reflecting clinical improvement when compared to the patients treated with the UVAR-XTS. Similar safety profile was observed between the two instruments based on a similar number of adverse events. Disclosures No relevant conflicts of interest to declare.

OC63 REQUEST REGISTRY: INTERIM RESULTS OF INTERNATIONAL MULTICENTRIC PROSPECTIVE REGISTRY FOR THE EVALUATION OF TRANSIT TIME FLOW MEASUREMENT AND INTRAOPERATIVE IMAGING IN CORONARY SURGERY

Abstract Background and Aim: Intraoperative graft failure is a well-recognized issue with a rate of 4–5% of incidence involving the 10% of patient submitted to CABG.Despite this evidence and the recommendation of international guidelines the routine use of intraoperative graft verification is low.The purpose of this multicentric prospective international registry was to assess the impact of routine use of Transit-Time Flow Measurement (TTFM) and High-Resolution Epicardial Ultrasonography (HR-ECUS) in CABG patients. Methods: The design of the study imposed to enroll 1000 patients in 7 centers (Italy,UK,USA,Canada,Germany,Netherlands) from 2015 to 2017.The inclusion criterium was the indication to isolated CABG operation in patient with at least 2-vessel disease.The study protocol and ethical approval was published in clinicaltrial.gov in February, 2015. The endpoints of the registry were: 1)any change in planned surgical procedure;2)type of change (aorta,coronary target, conduits,anastomosis);3)number and reason for the revision;4)in-hospital mortality and stroke. Results: total of 346 surgical strategy changes were registered in 249 (26%) patients.HR-ECUS leads to change in aorta manipulation sites in 10% of the patients,in coronary anastomotic site in 20% of the patients and the combined use of TTFM and HR-ECUS to 3% of intraoperative graft revision.The total number of adverse events was 1017 (22% mild,70% moderate,8% severe.The mortality rate was 0.5% with a stroke rate of 0.7%. Conclusions: In the hands of expert surgeons,high rate of optimal medical therapy use (&gt; 70%) and state-of-the-art surgical procedure the intraoperative guidance and graft verification of HR-ECUS and TTFM were associated with a 3% of revision rate and low-level of in-hospital mortality and stroke.

The Psychiatry Morbidity and Mortality Incident Reporting Tool Increases Psychiatrist Participation in Reporting Adverse Events.

Although the reporting of adverse events (AEs) is widely thought to be a key first step to improving patient safety in hospital systems, underreporting remains a common problem, particularly among physicians. We aimed to increase the number of safety reports filed by psychiatrists in our hospital system. We piloted an online survey for psychiatry-specific AE reporting, the Psychiatry Morbidity and Mortality Incident Reporting Tool (PMIRT) for a 1-year period. An e-mail prompt containing a link to the survey was sent on a weekly basis to all psychiatry department clinical staff. The primary outcome was the total number of events reported by psychiatrists through PMIRT; secondary outcomes were the total number of AEs and the number of serious harm events filed by psychiatrists in our hospital's formal event reporting system before and after implementation of the new protocol. Psychiatrists filed 65 reports in PMIRT during the study period. The average number of AEs reported by psychiatrists in the hospital's formal event reporting system significantly increased after the intervention (P = 0.0251), and the average number of serious harm events reported by psychiatrists increased nonsignificantly (P = 0.1394). The combination of an increase in awareness of event reporting with a psychiatry-specific AE reporting tool resulted in a significant improvement in the number of reports by psychiatrists.

Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis

Several secretagogues have been approved for the treatment of irritable bowel syndrome with constipation (IBS-C). However, their relative efficacy is unclear because there have been no head-to-head randomized controlled trials. We conducted a network meta-analysis to compare their efficacies in patients with IBS-C. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane Central Register of Controlled Trials through June 2018 to identify randomized controlled trials assessing the efficacy of secretagogues in adults with IBS-C. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random-effects model. Efficacy and safety of secretagogues were reported as a pooled relative risk with 95% confidence interval to summarize the effect of each comparison tested, and treatments were ranked according to their P score. We identified 15 eligible randomized controlled trials of secretagogues that included 8462 patients. Linaclotide, lubiprostone, plecanatide, and tenapanor were superior to placebo for the treatment of IBS-C. Linaclotide (290 μg once daily) was ranked first in efficacy based on the end point recommended by the Food and Drug Administration for trials in IBS-C, the primary end point used in each trial, abdominal pain, and complete spontaneous bowel movements. Tenapanor (50 mg twice daily) was ranked first for decreasing bloating. Total numbers of adverse events were significantly larger with linaclotide (290 and 500 μg once daily) and plecanatide (3 mg once daily) compared with placebo. However, plecanatide 6 mg once daily ranked first for safety. Diarrhea was significantly more common with all drugs, except lubiprostone (8 μg twice daily). Nausea was significantly more common in patients who received lubiprostone. In a network analysis of randomized controlled trials of secretagogues for IBS-C, we found all drugs to be superior to placebo. Efficacy was similar among individual drugs and dosages for most end points. However, data were extracted at the 12-week time point, so the long-term relative efficacy of these drugs is unknown.

Cannabinoids for the treatment of dementia

Background Dementia is a common chronic condition, mainly affecting older adults, characterised by a progressive decline in cognitive and functional abilities. Medical treatments for dementia are limited. Cannabinoids are being investigated for the treatment of dementia. Objectives To determine the efficacy and safety of cannabinoids for the treatment of dementia. Search methods We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialised Register - on 8 July 2021, using the terms cannabis or cannabinoid or endocannabinoid or cannabidiol or THC or CBD or dronabinol or delta-9-tetrahydrocannabinol or marijuana or marihuana or hashish. The register contains records from all major healthcare databases (the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources. Selection criteria We included all randomised controlled trials (RCTs) of cannabinoids for the treatment of dementia. We included participants of any age and of either sex with diagnosed dementia of any subtype, or with unspecified dementia of any severity, from any setting. We considered studies of cannabinoids administered by any route, at any dose, for any duration, compared with placebo, no treatment, or any active control intervention. Data collection and analysis Two review authors independently screened and selected studies for inclusion, extracted data, and assessed the risk of bias in included studies. When necessary, other review authors were involved in reaching consensus decisions. We conducted meta-analyses using a generic inverse variance fixed-effect model to derive estimates of effect size. We used GRADE methods to assess our confidence in the effect estimates. Main results We included four studies (126 participants) in this review. Most participants had Alzheimer's disease; a few had vascular dementia or mixed dementia. Three studies had low risk of bias across all domains; one study had unclear risk of bias for the majority of domains. The included studies tested natural delta-9-tetrahydrocannabinol (THC) (Namisol) and two types of synthetic THC analogue (dronabinol and nabilone). Three trials had a cross-over design. Interventions were applied over 3 to 14 weeks; one study reported adverse events over 70 weeks of follow-up. One trial was undertaken in the USA, one in Canada, and two in The Netherlands. Two studies reported non-commercial funding, and two studies were conducted with the support of both commercial and non-commercial funding. Primary outcomes in this review were changes in global and specific cognitive function, overall behavioural and psychological symptoms of dementia (BPSD), and adverse events. We found very low-certainty evidence suggesting there may be little or no clinically important effect of a synthetic THC analogue on cognition assessed with the standardised Mini-Mental State Examination (sMMSE) (mean difference (MD) 1.1 points, 95% confidence interval (CI) 0.1 to 2.1; 1 cross-over trial, 28 participants). We found low-certainty evidence suggesting there may be little or no clinically important effect of cannabinoids on overall behavioural and psychological symptoms of dementia assessed with the Neuropsychiatric Inventory (or its modified nursing home version) (MD -1.97, 95% CI -3.87 to -0.07; 1 parallel group and 2 cross-over studies, 110 participants). All included studies reported data on adverse events. However, the total number of adverse events, the total numbers of mild and moderate adverse events, and the total number of serious adverse events (SAEs) were not reported in a way that permitted meta-analysis. There were no clear differences between groups in numbers of adverse events, with the exception of sedation (including lethargy), which was more frequent among participants taking nabilone (N = 17) than placebo (N = 6) (odds ratio (OR) 2.83, 95% CI 1.07 to 7.48; 1 cross-over study, 38 participants). We judged the certainty of evidence for adverse event outcomes to be low or very low due to serious concerns regarding imprecision and indirectness. Authors' conclusions Based on data from four small, short, and heterogeneous placebo-controlled trials, we cannot be certain whether cannabinoids have any beneficial or harmful effects on dementia. If there are benefits of cannabinoids for people with dementia, the effects may be too small to be clinically meaningful. Adequately powered, methodologically robust trials with longer follow-up are needed to properly assess the effects of cannabinoids in dementia.

Intracervical foleys catheter: Can it serve as an alternative to standard pharmacological method of cervical ripening?

Background: Ripening of cervix is a prerequisite for successful labour induction. Use of prostaglandins for this purpose incurs a high risk of uterine hyperstimulation and a relatively higher cost of treatment. intracervical Foleys catheter insertion is a mechanical method stated in literature. The present study was to compare the efficacy and safety and cost of intracervical Foleys catheter balloon insertion with intracervical dinoprostone application for preinduction cervical ripening in patients requiring labour induction at term.Methods: This was a randomized, parallel group, active controlled study conducted in the obstetrics department of a tertiary care centre over a duration of one year. Group A received Dinoprostone cervical gel 0.5mg instilled in the cervical canal. Maximum of three doses (1.5mg dinoprostone) could be administered 6 hours apart. Patients randomized to group B were subjected to Foleys catheter insertion. Foleys catheter number 16 was used and balloon was inflated with 60ml of water. Primary efficacy parameter was change in Bishops score as compared to baseline and safety was monitored by comparing the total number of adverse events in the two groups.Results: Total of 89 patients were enrolled into the study during one year period out of which 45 received dinoprostone gel and 44 received Foleys catheter insertion respectively. Change in Bishops score, mode of delivery and total number of maternal and foetal adverse events did not differ significantly between the two groups.Conclusions: Efficacy and safety of Foleys catheter as a cervical ripening agent prior to induction of labour is comparable to dinoprostone gel. Since use of Foleys catheter is advantageous in terms of lack of specific storage conditions and cost of treatment, it could be considered a cost effective alternative for preinduction cervical ripening.

The impact of cumulative toxicity on physical quality of life in patients with metastatic colorectal cancer receiving first line chemotherapy.

3564 Background: We have previously suggested that treatment related toxicity has impact on physical quality of life (QOL) scores, as opposed to global QOL. Moreover, the cumulative effect of experienced toxicities, including low-grades AEs, may be of more importance. The purpose of this observational cohort study was to evaluate the association between cumulative toxicity and physical and global QOL in patients with metastatic colorectal cancer (mCRC) receiving chemotherapy. Methods: 105 patients with mCRC starting first line chemotherapy were evaluated. All patients completed the EORTC-QLQ-C30 questionnaire at baseline and after 10 weeks. Toxicity, clinical outcomes and demographics were retrieved from patient records. For each patient, we calculated cumulative toxicity in three different ways: i) total number of adverse events (AEs) (all grades), ii) total number of grade 3-4 AEs, and iii) total number of AEs multiplied by their grade. The relation between each cumulative toxicity score and QOL assessed at 10 weeks, was studied. Results: The mean age of patients was 64.8 ± 9.7 years, 70.5% were male, and 83.8% received first line oxaliplatin based combination chemotherapy. AEs occurred in 98.1% of patients, grade 3-4 AEs in 37.1%, and grade 1-2 AEs in 61.0%. The mean number of experienced AEs (all grades) was 5.3 ± 2.7. The most common toxicities included diarrhea, neuropathy and fatigue. None of the toxicity scores was related to global QOL outcome. A higher total number of all grades AEs (β = - 2.2, 95%CI = -3.7; -6.6) and total number of AEs multiplied by grade (β = -1.3, 95%CI = -2.2; -3.5) were significantly associated with worse physical QOL. Conclusions: Cumulative toxicity, defined as the total of all grades AEs, significantly affects physical QOL in patients with mCRC receiving first line chemotherapy. Improvement of treatment related toxicity management by reducing the total number of AEs, may result in relevant improvements in patients’ QOL. Our results emphasize that future RCTs should present physical QOL outcomes instead of global QOL, as well as all grades and total number of toxicities for individual patients.