Pooled Safety Research Articles

A qualitative analysis of parents' beliefs about portable pool safety behaviours.

The aim of this study was to develop an in-depth understanding of the beliefs parents hold regarding portable pool safety behaviours using the theory of planned behaviour (TPB). Semi-structured interviews were conducted with parents (N = 15) of children aged 5 years and younger who owned a portable pool. Interviews examined three key safety behaviours: supervising within arms' reach, fencing portable pools deeper than 30 cm, and emptying and storing portable pools safely after use. Parents identified a range of advantages, disadvantages, normative influences, and facilitators and barriers towards the three behaviours. The identification of these salient behavioural, normative, and control beliefs enrich limited understandings of portable pool safety behaviours of parents with young children. Current findings fill a knowledge gap in portable pool safety and provide potential targets for messages to improve parents' behaviours for their young children around portable pools in the hope of preventing loss of life.

Drowning Among Children 1-4Years of Age in California, 2017-2021.

Drowning, the leading cause of unintentional injury death among California children less than five years of age, averaged 49 annual fatalities for the years 2010-2021. The California Pool Safety Act aims to reduce fatalities by requiring safety measures around residential pools. This study was designed to analyze annual fatality rates and drowning incidents in California among children 1-4years of age from 2017-2021. We identified fatalities, injury hospitalizations, and emergency department (ED) visits from California state vital statistics death data and state hospital and ED discharge data using the EpiCenter California Injury Data Online website. Over the five-year study period, 4,166 drowning incidents were identified: 234 were fatalities, 846 were hospitalizations, and 3,086 were ED visits. The observed difference in fatality rates from 2017 to 2021 failed to achieve statistical significance (P = 0.88). Location-based analysis of the 234 fatal drowning incidents revealed that pools were the most common injury site, accounting for 65% of the cases. Drowning remains the leading cause of unintentional, injury-related death among California children 1-4years of age, as the annual rate of fatality over the five-year study period did not decline. While the EpiCenter California Injury Data Online website is excellent for analyzing annual rates of drowning incidents among California residents over time, it is limited in providing insight into modifiable risk factors and event circumstances that can further inform prevention. The development of robust integrated fatal and non-fatal local, state, and national systematic data collection systems could aid in moving the needle in decreasing pool fatalities among young children.

811. POOLED 1-YEAR SAFETY AND QUALITY-OF-LIFE DATA AFTER REFLUXSTOP SURGERY AT TWO LARGE HOSPITALS IN SWITZERLAND: A RETROSPECTIVE CHART ANALYSIS

Abstract Background The standards of care in reflux disease management are proton pump inhibitor (PPI) therapy and conventional antireflux surgery, however, both options carry the caveats of medication irresponsiveness and troublesome postoperative sequelae, respectively. More specifically, PPIs respond inadequately in up to 40% of cases and Nissen fundoplication is associated with postoperative dysphagia in a significant proportion of patients. RefluxStop is an innovative technology that was adopted at our two respective institutions following promising safety and effectiveness data from its CE mark trial. We present the pooled safety and quality-of-life data of our 1-year experience with RefluxStop surgery. Methods Between September 2018 and August 2023, RefluxStop surgery was performed on 121 patients as part of routine clinical care at two hospitals, both of which are high-volume centers for antireflux surgery. The procedure involves crural repair with hiatal hernia reduction, reconstruction of the flap valve and angle of His, narrow esophagogastric (90-110°) plication, and device implantation in an external pouch on the gastric fundus (Figure 1). A retrospective chart analysis was conducted to document perioperative adverse events (AEs) and quality-of-life improvements via Gastroesophageal Reflux Disease Health-Related Quality of Life (GERD-HRQL) score. Higher GERD-HRQL scores are indicative of more severe disease. Results Baseline patient characteristics included mean age 54.7 years, female sex (52.9%), body mass index 27.2±4.1 kg/m2, large hiatal hernia >3 cm (46.3%) of median (IQR) size 3 (2-5) cm, abnormal esophageal motility (60.3%), and Barrett’s esophagus (27.3%). At 1-year follow-up, patients experienced a median (IQR) reduction of 90.5% (81.4-100%) in total GERD-HRQL score. Intraoperative AEs included conversion to laparotomy for adhesiolysis with bleeding (n=1), bleeding short gastric arteries leading to return to the operating room the next day (n=1), and esophageal perforation repaired intraoperatively (n=1). Postoperative AEs are summarized in Table 1. Conclusion The results of this pooled retrospective chart analysis support the promising early data of the RefluxStop CE mark trial. Few and predictable AEs occurred during the study period while significant improvements in quality of life were observed, as evidenced by 90.5% (81.4-100%) reductions in GERD-HRQL score. Notably, this pooled cohort of patients was comprised of substantial proportions of difficult-to-treat patients (i.e., abnormal esophageal motility in 60.3%, large hiatal hernia >3 cm in 46.3%), providing evidence for wider implementation of RefluxStop surgery in real-world settings. Additional evaluation is required to further delineate the role of this promising innovative antireflux surgery.

An Environmental Audit of Aracari Resort

Tourism impacts the economy, the natural and built environment, the immediate population, and even tourists – the very resource needed by the industry to remain viable. Regular assessment of the environmental performance of the industry is necessary to ascertain compliance with national standards and regulations. This is achieved with an environmental audit. To this end, an environmental audit was conducted at the Aracari Resort, almost a decade after it began operations. The Resort’s operations should have minimal impact on public health and the environment, as evidenced by good sanitation, safety measure implementation, and adherence to the Public Health Legislation and Occupation Health & Safety Act. The methodology used included monitoring of water quality and use, noise, and energy; and direct observation of waste and safety management. The results showed that water quality parameters such as pH, temperature, phosphorus and ammonium were in compliance with the national effluent discharge guidelines; however, chlorides, chemical oxygen demand, and total suspended solids were not. Water metre readings revealed an average daily water consumption of 22.5m3 and an average weekly water consumption of 135m3. Noise produced from the Resort was in compliance with the daytime limits of 75 dB based on the national standard, but exceeded residential nighttime limits (from Friday to Sunday) of 60 dB. The average (55.6 kW), maximum (83.85 kW), and minimum (51.9 kW) power demands across a 7-day period were obtained from Fluke Monitoring System readings. Solid waste management was observed to be inadequate on days of planned events, with overflowing bins evident on the premises. Safety measures were implemented for food, chemical handling and storage, swimming pool safety, and fire safety, which were observed to be consistent with the standards. The facility’s overall performance was satisfactory based on the evaluation criteria, and some environmental practices of Aracari Resort conformed to the Environmental Protection Agency requirements and other established guidelines. Areas identified for improved compliance and enhanced environmental management included the implementation of an environmental policy, regular monitoring of environmental parameters, and staff training on the terms and conditions of the Environmental Permit.

Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.

How IoT improves pool safety and management in the hotel sector

Pool monitoring is emerging as an integral component in the management of aquatic facilities, such as hotels, resorts and recreational centres, where pools play a central role in the guest experience. This advanced technology provides a proactive platform for maintaining the safety, hygiene and optimal operation of these recreational and relaxation spaces.

Antiarrhythmic drug therapy and catheter ablation in patients with paroxysmal or persistent atrial fibrillation: a systematic review and meta-analysis

BackgroundCatheter ablation and antiarrhythmic drug therapy are utilized for rhythm control in atrial fibrillation (AF), but their comparative effectiveness, especially with contemporary treatment modalities, remains undefined. We conducted a systematic review and meta-analysis contrasting current ablation techniques against antiarrhythmic medications for AF.MethodsWe searched PubMed, SCOPUS, Cochrane CENTRAL, and Web of Science until November 2023 for randomized trials comparing AF catheter ablation with antiarrhythmics, against antiarrhythmic drug therapy alone, reporting outcomes for > 6 months. Four investigators extracted data and appraised risk of bias (ROB) with ROB 2 tool. Meta-analyses estimated pooled efficacy and safety outcomes using R software.ResultsTwelve trials (n = 3977) met the inclusion criteria. Catheter ablation was associated with lower AF recurrence (relative risk (RR) = 0.44, 95%CI (0.33, 0.59), P ˂ 0.0001) and hospitalizations (RR = 0.44, 95%CI (0.23, 0.82), P = 0.009) than antiarrhythmic medications. Catheter ablation also improved the physical quality of life component score (assessed by a 36-item Short Form survey) by 7.61 points (95%CI -0.70-15.92, P = 0.07); but, due to high heterogeneity, it was not statistically significant. Ablation was significantly associated with higher procedural-related complications [RR = 15.70, 95%CI (4.53, 54.38), P < 0.0001] and cardiac tamponade [RR = 9.22, 95%CI (2.16, 39.40), P = 0.0027]. All-cause mortality was similar between the two groups.ConclusionsFor symptomatic AF, upfront catheter ablation reduces arrhythmia and hospitalizations better than continued medical therapy alone, albeit with moderately more adverse events. Careful patient selection and risk-benefit assessment are warranted regarding the timing of ablation.

Long-term pooled safety analysis of tislelizumab as monotherapy or in combination with chemotherapy in patients with advanced cancers.

e14617 Background: The PD-1 inhibitor tislelizumab (TIS) has demonstrated efficacy and tolerability in patients (pts) with advanced cancers. To evaluate long-term safety of TIS as monotherapy (mono) or in combination (combo) with chemotherapy in pts with advanced gastrointestinal (GI) and lung cancers, data were pooled from 8 pivotal phase III studies conducted between 2017 and 2023. Methods: 2636 adult pts with GI (n=1415) or lung (n=1221) cancers and an ECOG PS of 0-1, who received ≥1 dose of study drug, were included. Endpoints included immune-mediated adverse events (imAEs) by tumor type, treatment (Tx) duration, and race. Early and delayed imAEs, defined as occurring within 1 year (yr) and &gt;1 yr after starting TIS, respectively, were also evaluated. Results: Median (range) Tx duration in the GI and lung cancer studies was 4.9 (0.1-50.4) and 6.2 (0.2-44.9) months, respectively, with 20.9% and 29.6% of pts, respectively, having ≥1 yr exposure. Most pts were Asian (GI mono: 76.4%; GI combo: 74.9%; lung mono: 79.2%; lung combo: 100%). ImAEs occurred in 32.5% of pts in the GI mono and combo studies (Table); most were low grade, with grade ≥3 imAEs reported in 6.2% (mono) and 8.2% (combo) of pts. Incidence of imAEs in the mono and combo lung studies, respectively, was 34.3% and 43.7% (grade ≥3: 6.4% and 9.6%). ImAE incidence was comparable between Asian and White race subgroups, respectively, in the GI mono (33.6% vs 29.5%), GI combo (34.9% vs 23.9%), and lung mono (35.5% vs 32.3%) studies. Most imAEs occurred within 1 yr of starting TIS in the GI (mono: 32.0%; combo: 32.4%) and lung (mono: 34.1%; combo: 42.2%) studies. Delayed imAEs occurred less often than early imAEs; of pts still on Tx or in study follow-up 1 yr after initial Tx, 54/757 (7.1%) in GI studies and 86/804 (10.7%) in lung studies experienced a delayed imAE. Frequently reported imAEs were consistent, regardless of time of onset (early vs delayed). Conclusions: This long-term, retrospective, pooled analysis supports TIS as a tolerable Tx for pts with advanced GI and lung cancers. Delayed imAEs were relatively infrequent and were consistent with the established safety profile of TIS. Clinical trial information: NCT03412773 ; NCT03430843 ; NCT03358875 ; NCT03663205 ; NCT03777657 ; NCT03783442 ; NCT03594747 ; NCT04005716 . [Table: see text]

The role of immune checkpoint blockade in children, adolescents, and young adults: A systematic review and meta-analysis.

10057 Background: Immune checkpoint blockade (ICB) has changed the treatment landscape for many types of adult cancer. However, while certain subsets of cancer in children, adolescents, and young adults (CAYA) are ICB-responsive, ICBs are less routinely used in clinical practice, thus clinical experience lags behind that of adults. Therefore, we performed a systematic review and meta-analysis to evaluate the safety and efficacy of ICB in the CAYA population. Methods: PubMed, Cochrane and Embase libraries were systematically searched for clinical trials evaluating ICB therapies for cancer in CAYA patients. We excluded reviews, case reports, observational studies, retrospective studies, studies with overlapping populations, trials with no outcomes of interest, and studies enrolling the adult populations (&gt;40 years). We pooled the prevalence of treatment-related adverse events (TRAE), objective response rate (ORR), stable disease (SD), and their corresponding 95% confidence intervals (95% CI). For ORR and TRAE endpoints, we performed a subgroup analysis of each drug (PD-1, PD-L1 and CTLA-4) and each tumor type. A comparative analysis of the reported median overall survival (OS) and progression-free survival (PFS) was also completed. Statistical analysis was performed using R software version 4.3.1 and heterogeneity was evaluated through I2 statistics. Results: From 3,753 initial studies, 15 clinical trials were included, comprising 797 patients with median age ranging from 6.5 to 16.0 years (1-30 years) and multiple types of hematologic and solid malignancies. An all-grade TRAE rate of 66% was found (95% CI 60-71), while the proportion of grade 3/4 TRAE was 19% (95% CI 13-27). In the tumor type subgroup analysis for all-grade TRAE and grade 3/4 TRAE, solid tumors had the highest rates; 92% (95% CI 41-99) and 50% (95% CI 14-42), respectively. Central nervous system tumors had all-grade and grade 3/4 TRAE rates of 61% (95% CI 53-68) and 21% (95% CI 12-33), respectively. Fatigue, anemia, and nausea were the most frequently reported TRAE. The ORR was 13% (95% CI 5-27) (82 of 531 patients). For drug class and tumor type subgroup analysis, PD-1 inhibitors and lymphoma presented the highest proportion of ORR, with 25% (95% CI 8-56) and 59% (95% CI 23-87), respectively. SD was noted in 21% (95% CI 14-30) of patients (97 of 467 patients). Median OS, available for 300 patients, ranged from 4.4 to 23.7 months, while median PFS, available for 299 patients, ranged from 1.2 to 6.2 months. Conclusions: This study suggests that ICB is well tolerated in CAYA patients with different cancer types. As previously reported in the literature, certain subsets of CAYA cancer are ICB-responsive. This pooled safety data supports the continued investigation of ICB in CAYA patients most likely to benefit from ICB therapy, including advancing ICB into combination strategies.

Bacteriological Safety of Swimming Pools Within and Around the University of Port Harcourt

Bacteriological Safety of Swimming Pools Within and Around the University of Port Harcourt

Study on spent fuel heatup during spent fuel pool complete loss of coolant accident

Abstract After years of operation, nuclear power plants accumulate a substantial amount of spent fuel stored in spent fuel pools. Prior to the completion of dry storage facilities, this spent fuel remains in the spent fuel pools for several decades. The progression of accidents in spent fuel pools leading to fuel damage typically spans several days or even weeks, which may lead people to overlook the importance of spent fuel pool safety. However, accidents involving spent fuel pools have a characteristic of low probability but high consequences. Their significance has been reemphasized, especially after the Fukushima accident. This study conducts an analysis of the scenario where a spent fuel pool experiences a complete loss of water. A plant equipped with a BWR-4 reactor and a MARK-I containment structure is used as the reference plant. The analysis utilizes the MAAP5 code to assess the impact of different fuel cooling times and ventilation flow rate of secondary containment building on the fuel temperature variation, considering only air circulation for cooling. Based on the analysis results, the plant utilizes the normal ventilation system of the reactor building, which can maintain the fuel temperature below 565 °C with a cooling time of 1 year. Additionally, it was found in the study that adequate ventilation flow rates and sufficient cooling time can ensure that the fuel temperature remains below 565 °C, thereby preserving fuel integrity.

Evolocumab Treatment in Pediatric Patients With Homozygous Familial Hypercholesterolemia: Pooled Data From Three Open-Label Studies.

Pediatric patients with homozygous familial hypercholesterolemia (HoFH) have an increased risk of atherosclerotic cardiovascular disease and difficulty meeting low-density lipoprotein cholesterol (LDL-C) goals. In this post hoc analysis, we evaluated pooled safety and efficacy data from 3 studies in pediatric patients with HoFH treated with the PCSK9 (proprotein convertase subtilisin/kexin type 9) monoclonal antibody inhibitor evolocumab. Patients with HoFH aged 10 to 17 years received treatment with open-label evolocumab 420 mg subcutaneously monthly or biweekly in the TAUSSIG, RAMAN, or HAUSER-OLE clinical studies. All patients received background statins with or without ezetimibe. Study duration ranged from 12 to 260 weeks. The primary end point was treatment-emergent adverse events per 100 patient-years. Efficacy end points were changes from baseline to week 12 in lipids and PCSK9. Of the 39 patients in the pooled analysis, 69.2% were males, median age was 13.0 years, and 79.5% (31/39) had genotyped HoFH with LDLR pathogenic variants. Overall, median exposure to evolocumab was 18.2 (Q1, Q3: 3.0, 18.5) months. Treatment-emergent adverse events with an exposure-adjusted patient incidence rate of ≥5% were upper respiratory tract infection (6.6%), influenza (5.2%), and acne (5.0%) per 100 patient-years. Exposure-adjusted patient incidence of serious treatment-emergent adverse events was 13.3% per 100 patient-years. Excluding 4 patients receiving lipoprotein apheresis, week 12 median percentage change from baseline in LDL-C was -2.9% (Q1, Q3: -21.7, 1.5); however, 42.9% (15/35) of patients achieved ≥15% reduction in LDL-C from baseline. Residual LDLR (LDL receptor) activity was not associated with a reduction in LDL-C. In this pooled data analysis from 3 studies in pediatric patients with HoFH, evolocumab was well tolerated, with no new safety signals reported. These safety findings are consistent with findings from previous studies of evolocumab. Patients showed marked variability in LDL-C reduction. Results from this pooled analysis support guidelines suggesting a trial of PCSK9 inhibitor therapy regardless of estimated residual LDLR function. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01624142, NCT03403374, and NCT02624869.

A systematic review with meta‐analysis: Efficacy and safety of potassium‐competitive acid blocker compared with proton pump inhibitor in the maintenance of healed erosive esophagitis

AbstractIntroductionProton pump inhibitor (PPI) is the mainstay therapy for the maintenance of healed erosive esophagitis (EE). It is unknown whether potassium‐competitive acid blockers (PCABs) are more efficacious and safer than PPIs.MethodsOnly randomized controlled trials (RCTs) comparing PCABs to PPIs in the maintenance of healing rates of endoscopically proven healed EE and indexed in MEDLINE, EMBASE, and CENTRAL until 3 February 2024, were included. A fixed‐effects model meta‐analysis was performed to pool primary efficacy outcome (maintenance of healing rates at week 24) and safety data (any treatment‐emergent adverse event or TEAE). The risk of bias was assessed using Cochrane's Risk of Bias 2 (RoB2) tool.ResultsFour RCTs with a total of 2554 patients were eligible for inclusion. All trials were of low risk of bias. Compared to lansoprazole 15 mg, the maintenance rates of healed EE at week 24 were significantly higher with vonoprazan 10 mg (RR 1.13; 95% CI 1.07–1.19) and vonoprazan 20 mg (RR 1.15; 95% CI 1.10–1.21). Likewise, compared to lansoprazole 15 mg, any TEAEs were significantly greater with vonoprazan 20 mg (RR 1.10; 95% CI 1.01–1.20) but not vonoprazan 10 mg.ConclusionVonoprazan 10 and 20 mg were superior to lansoprazole 15 mg in the maintenance of the healing of EE. Any TEAEs were greater with vonoprazan 20 mg.

Therapeutic Vaccines for Follicular Lymphoma: A Systematic Review.

(1) Background: We aimed to estimate the pooled effectiveness and safety of vaccination in follicular lymphoma (FL) and discuss implications for immunotherapy development. (2) Methods: We included randomized trials (RCTs) of therapeutic vaccines in patients with FL. Progression-free survival (PFS) was the primary outcome. We searched databases (PubMed, Embase, Scopus, Web of Science Core, medRxiv) and registries (PROSPERO, CENTRAL, ClinicalTrials.gov, EuCTR, WHO ICTRP) and conducted online, citation, and manual searches. We assessed risks of bias across outcomes using RoB 2.0 and across studies using ROB-ME and a contour-enhanced funnel plot. (3) Results: Three RCTs were included (813 patients, both previously treated and untreated). Patients with a complete or partial response after chemotherapy were randomized to either a patient-specific recombinant idiotype keyhole limpet hemocyanin (Id-KLH) vaccine plus granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo immunotherapy (KLH + GM-CSF). Meta-analyses showed that PFS was worse with the vaccine, but not significantly: hazard ratio, 1.09 (95% CI 0.91-1.30). The GRADE certainty of evidence was moderate. Adverse event data were mixed. (4) Conclusions: We are moderately certain that Id-KLH results in little to no difference in PFS in FL. (5) Funding: Russian Science Foundation grant #22-25-00516. (6) Registration: PROSPERO CRD42023457528.

Vonoprazan is superior to lansoprazole for healing of severe but not mild erosive esophagitis: A systematic review with meta-analysis of randomized controlled trials.

Healing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60-70%). Vonoprazan, a potassium-competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta-analysis compares the efficacy and safety of vonoprazan 20mg versus lansoprazole 30mg daily in healing EE, specifically in those with LA Grade C/D. We searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20mg daily or lansoprazole 30mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed-effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location. Four randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20mg was superior to lansoprazole 30mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169-1.433], Week 4 1.160 [1.059-1.270], and Week 8 1.175 [95% CI 1.107-1.247]), but was similar for mild EE at all weeks (P-interaction<0.01). Vonoprazan 20mg was more efficacious than lansoprazole 30mg at Week 8 in Western versus Asian studies (P-interaction<0.01). Any, serious, and drug-related treatment-emergent adverse events were comparable between groups. Vonoprazan 20mg is superior to lansoprazole 30mg for healing severe EE but not mild EE. Vonoprazan 20mg daily has a similar safety profile to lansoprazole 30mg daily.

Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis Through 5 Years in Crohn's Disease and 4 Years in Ulcerative Colitis.

Previously published long-term safety data reported a favourable ustekinumab safety profile for the treatment of inflammatory bowel disease [IBD]. We present the final cumulative safety data from pooled ustekinumab IBD phase 2/3 clinical studies through 5 years in Crohn's disease [CD] and 4 years in ulcerative colitis [UC]. In phase 3 studies, patients received a single intravenous placebo or ustekinumab [130 mg or ~6 mg/kg] induction dose followed by subcutaneous maintenance doses of placebo or ustekinumab [90 mg q8w or q12w]. Analyses included all patients who received one dose of study treatment and included patients who were biologic-naïve and patients with a history of biologic failure. Safety outcomes are summarized and presented using number of events per 100 patient-years of follow-up and corresponding 95% confidence intervals. In this final pooled safety analysis, 2575 patients were treated with ustekinumab with 4826 patient-years of follow-up. Rates of key safety events, including major adverse cardiac events and malignancies, were similar between placebo and ustekinumab or not higher for ustekinumab. Opportunistic infections, including tuberculosis, and malignancies were reported infrequently. Rates of key safety events in the IBD group were no higher in the ustekinumab group than in the placebo group for both patients who were biologic-naïve or who had a history of biologic failure. No lymphomas or cases of posterior reversible encephalopathy syndrome [formerly known as reversible posterior leukoencephalopathy syndrome] were reported. The final cumulative ustekinumab safety data through 5 years in CD and 4 years in UC demonstrated favourable safety compared to placebo and continue to support the well-established safety profile across all approved indications. NCT00265122, NCT00771667, NCT01369329, NCT01369342, NCT01369355, NCT02407236.

Stem Cell Treatment and Cerebral Palsy: A Systematic Review and Meta-Analysis.

We designed this systematic review and meta-analysis to estimate the pooled efficacy and safety profile of different types of stem cells in treating patients with cerebral palsy (CP). We systematically searched PubMed, Scopus, EMBASE, Web of Science, Google Scholar, and also gray literature, including references of the included studies which were published before November 2021. We extracted data regarding the total number of participants, first author, publication year, country of origin, mean age, cell type, cell dose, cell source, method of transplantation, duration of follow-up, Gross motor function, Ashworth scale, and adverse events. We found 2073 articles by literature search; after deleting duplicates, 1194 remained. Nine articles remained for meta-analysis. The SMD of GMF-66 score (after-before) treatment was 1.5 (95% CI:0.7-2.3) (I2 = 89.9%, P < 0.001). The pooled incidence of Gastrointestinal (GI) complications after transplantation was 21% (95% CI:9-33%) (I2 = 56%, P = 0.08). The pooled incidence of fever after transplantation was 18 % (95% CI:6-30%) (I2 = 87.9%, P = 0.08 < 0.001) Conclusion: The result of this systematic review and meta-analysis show that stem cell therapy in cerebral palsy has neuroprotective properties from anti-inflammatory and anti-apoptotic activities. Stem cell therapy seems to be a promising adjunct to traditional therapies for cerebral palsy patients.

Physicochemical and bacteriological quality of swimming pools water in Kombolcha Town, Northeastern Ethiopia.

The use of swimming pool water for recreation, rehabilitation, and athletics is widespread around the world, especially in large Cities and Towns. However, poorly managed swimming pool water can facilitate the spread of illnesses connected to recreational water. Despite this, there is no evidence on quality of swimming pools water in Kombolcha Town. Therefore, this study was aimed to evaluate the physicochemical and bacteriological quality of swimming pools water in Kombolcha Town. A laboratory-based cross-sectional study was conducted from February to April, 2021 in Kombolcha Town. A total of 90 water samples were collected from the three outdoor swimming pools. The collected data of both physicochemical and bacteriological parameters were entered into Microsoft Excel 2010 and analyzed using SPSS version 25.0. One-way ANOVA was used to test whether there were statistically significant differences between different swimming pools. The level of significance was declared at a p-value of <0.05. In this study, out of all the pool water samples that were examined, 37.8% had pH values between 7.2 and 7.8, 36.7% had temperatures between 21°C and 32°C, and 26.7% had turbidity values that were within the WHO standard. Furthermore, only 16.7% of the pool water samples showed residual chlorine levels of 2-3 mg/L. In addition, only 27.8, 35.6, and 32.2% of the samples, respectively, met the WHO criterion for total coliform, fecal coliform, and heterotrophic plate count. The result indicates that most pool water samples did not fulfill both the physicochemical and bacteriological quality of the WHO standard limit for swimming pools. Thus, it is crucial to clean and regularly check the pool water, apply pool safety requirements, and raise pool user's awareness about the danger of pool water pollution through training.

Pooled analysis of routine safety parameters observed in healthy participants at baseline and following placebo administration in early phase clinical studies.

Phase I trials inform on the initial safety profile of a new molecule and impact whether further development is pursued or not. Understanding the effect of non-pharmacological factors on the variability of routine safety parameters could improve decision making in these early clinical trials, helping to separate signals related to the new molecule from background "noise." To understand the impact of non-pharmacological factors on routine safety parameters, we evaluated pooled safety data from over 1000 healthy participants treated with placebo in phase I trials between 2009 and 2018. The phase I participants were predominantly men, less than or equal to 50 years, White, and non-Hispanic; and approximately an equal proportion had body mass index in the normal and overweight/obese range. Following administration of placebo, vital signs, electrocardiogram, and laboratory parameters remained near predose baseline values. Large changes from baseline were observed for many safety parameters, but these occurred in a relatively small number of participants. At least one adverse event (AE) occurred in 49.7% of participants receiving placebo in single ascending dose (SAD) studies and in 72.4% of participants receiving placebo in multiple ascending dose (MAD) studies, with headache being the most commonly reported AE (18.7% in SAD and 28.3% in MAD studies). Overall, these analyses are consistent with non-pharmacological factors having a small impact on routine safety parameters in a phase I trial. The provided supplemental data may be used to contextualize the magnitude and frequency of abnormal safety values and AEs observed in phase I trials.

Robustness of Longitudinal Safety and Efficacy After Paclitaxel-Based Endovascular Therapy for Treatment of Femoro-Popliteal Artery Occlusive Disease: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

The aims of this study were: i) to assess fragility indices (FIs) of individual randomized controlled trials (RCTs) that compared paclitaxel-based drug-coated balloons (DCBs) or drug-eluting stents (DESs) versus standard endovascular devices, and ii) to meta-analyze mid-term and long-term safety and efficacy outcomes from available RCT data while also estimating the FI of pooled results. This systematic review has been registered in the PROSPERO public database (CRD42022304326 http://www.crd.york.ac.uk/PROSPERO). A query of PubMed (Medline), EMBASE (Excerpta Medical Database), Scopus, and CENTRAL (Cochrane Central Register of Controlled Trials) databases was performed to identify eligible RCTs. Rates of primary patency (PP) and target lesion revascularization (TLR) were assessed as efficacy outcomes, while lower limb amputation (LLA) consisting of major amputation that is. below or above the knee and all-cause mortality were estimated as safety outcomes. All outcomes were pooled with a random effects model to account for any clinical and study design heterogeneity. The analyses were performed by dividing the RCTs according to their maximal follow-up length (mid-term was defined as results up to 2-3years, while long-term was defined as results up to 4-5years). For each individual outcome, the FI and reverse fragility index (RFI) were calculated according to whether the outcome results were statistically significant or not, respectively. The fragility quotient (FQ) and reverse fragility quotient (RFQ), which are the FI or RFI divided by the sample size, were also calculated. A total of 2,337 patients were included in the systematic review and meta-analysis. There were 2 RCTs examining DES devices and 14 RCTs evaluating different DCBs. For efficacy outcomes, there was evidence that paclitaxel-based endovascular therapy increased the PP rate and reduced the TLR rate at mid-term, with a calculated pooled risk ratio (RR) of 1.66 for patency (95% CI, 1.55-1.86; P<0.001), with a corresponding number needed-to-treat (NNT) of 3 patients (95% CI, 2.9-3.8) and RR of 0.44 for TLR (95% CI, 0.35-0.54; P=0.027), respectively. Similarly, there was evidence that paclitaxel-based endovascular therapy both increased PP and decreased TLR rates at long-term, with calculated pooled RR values of 1.73 (95% CI, 1.12-2.61; P=0.004) and 0.53 (95% CI, 0.45-0.62; P=0.82), respectively. For safety outcomes, there was evidence that paclitaxel-based endovascular therapy increased all-cause mortality at mid-term, with a calculated pooled RR of 2.05 (95% CI, 1.21-3.24). However, there was no difference between treatment arms in LLA at mid-term (95% CI, 0.1-2.7; P=0.68). Similarly, neither all-cause mortality nor LLA at long-term differed between treatment arms, with a calculated pooled RR of 0.66, 1.02 (95% CI, 0.31-3.42) and 1.02 (95% CI, 0.30-5.21; P=0.22), respectively. The pooled estimates of PP at mid-term were robust (FI=28 and FQ=1.9%) as were pooled rates of TLR (FI=18 and FQ=0.9%). However, when safety outcomes were analyzed, the robustness of the meta-analysis decreased significantly. In fact, the relationship between the use of paclitaxel-coated devices and all-cause mortality at mid-term showed very low robustness (FI=4 and FQ=0.2%). At 5years, only the benefit of paclitaxel-based devices to reduce TLR remained robust, with an FI of 32 and an FQ of 3.1%. The data supporting clinical efficacy endpoints of RCTs that examined paclitaxel-based devices in the treatment of femoral-popliteal arterial occlusive disease were robust; however, the pooled safety endpoints were highly fragile and prone to bias due to loss of patient follow-up in the original studies. These findings should be considered in the ongoing debate concerning the safety of paclitaxel-based devices.