Revisiting established medicines: An overview of systematic reviews about ibuprofen and paracetamol for treating pain in children

Background and objective: We explored how systematic reviews evaluated paracetamol and ibuprofen for treating pain in children, as these two non-opioid analgesics are well-established medicines included in most national essential medicines lists. Databases and data treatment: We carried out an overview of systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions (PROSPERO registration: 42016045367). We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (CDSR) and Database of Reviews of Effects (DARE) up to 23 August 2017. We used AMSTAR checklist to analyse methodological quality of included SRs. Results: We found 17 SRs with 72 unique RCTs; the majority of those trials included under 100 children. Positive conclusive evidence was found in only one SR, regarding safety of paracetamol. Conclusions of other SRs for efficacy and safety of ibuprofen and paracetamol were inconclusive, unclear, or there was no opinion. Only one SR analysed efficacy of ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) in chronic pain and the conclusion was that there was no evidence from RCTs that NSAIDs were effective for chronic non-cancer pain in children and adolescents. Most of the SRs addressed very narrow questions, included few trials, with few children and were of low or medium methodological quality. Conclusions: Most SRs on two relevant medicines have inconsistent conclusions and doubt upon their effectiveness. Instead of focusing on very narrow questions, SRs should examine more comprehensive research topics to obtain a general sense of consistency, particularly when analysing established medicines. Significance: Evidence behind two analgesics—ibuprofen and paracetamol—that are well-established medicines for children in most countries appears limited, judging by the systematic reviews. The discrepancy between clinical use and the extensive evidence we reviewed may be a result of the selective criteria in the reviews examined. We need new, and better evidence syntheses supporting the use of these two medicines in wide indications regarding pain in children

Application for White Spot Syndrome Virus (WSSV) Monitoring using Edge Machine Learning

The aquaculture industry, strongly reliant on shrimp exports, faces challenges due to viral infections like the White Spot Syndrome Virus (WSSV) that severely impact output yields. In this context, computer vision can play a significant role in identifying features not immediately evident to skilled or untrained eyes, potentially reducing the time required to report WSSV infections. In this study, the challenge of limited data for WSSV recognition was addressed. A mobile application dedicated to data collection and monitoring was developed to facilitate the creation of an image dataset to train a WSSV recognition model and improve country-wide disease surveillance. The study also includes a thorough analysis of WSSV recognition to address the challenge of imbalanced learning and on-device inference. The models explored, MobileNetV3-Small and EfficientNetV2-B0, gained an F1-Score of 0.72 and 0.99 respectively. The saliency heatmaps of both models were also observed to uncover the "black-box" nature of these models and to gain insight as to what features in the images are most important in making a prediction. These results highlight the effectiveness and limitations of using models designed for resource-constrained devices and balancing their performance in accurately recognizing WSSV, providing valuable information and direction in the use of computer vision in this domain.Comment: 6 pages, 7 figures, conferenc

The evidence for services to avoid or delay residential aged care admission: A systematic review

Background Interventions that enable people to remain in their own home as they age are of interest to stakeholders, yet detailed information on effective interventions is scarce. Our objective was to systematically search and synthesise evidence for the effectiveness of community-based, aged care interventions in delaying or avoiding admission to residential aged care. Method Nine databases were searched from January 2000 to February 2018 for English publications. Reference lists of relevant publications were searched. The databases yielded 55,221 citations and 50 citations were gleaned from other sources. Where there was sufficient homogeneity of study design, population, intervention and measures, meta-analyses were performed. Studies were grouped by the type of intervention: complex multifactorial interventions, minimal/single focus interventions, restorative programs, or by the target population (e.g. participants with dementia). Results Data from 31 randomised controlled trials (32 articles) that met our inclusion criteria were extracted and analysed. Compared to controls, complex multifactorial interventions in community aged care significantly improved older adults’ ability to remain living at home (risk difference − 0.02; 95% CI -0.03, − 0.00; p = 0.04). Commonalities in the 13 studies with complex interventions were the use of comprehensive assessment, regular reviews, case management, care planning, referrals to additional services, individualised interventions, frequent client contact if required, and liaison with General Practitioners. Complex interventions did not have a significantly different effect on mortality. Single focus interventions did not show a significant effect in reducing residential aged care admissions (risk difference 0, 95% CI -0.01, 0.01; p = 0.71), nor for mortality or quality of life. Subgroup analysis of complex interventions for people with dementia showed significant risk reduction for residential aged care admissions (RD -0.05; 95% CI -0.09, -0.01; p = 0.02). Compared to controls, only interventions targeting participants with dementia had a significant effect on improving quality of life (SMD 3.38, 95% CI 3.02, 3.74; p \u3c 0.000001). Conclusions Where the goal is to avoid residential aged care admission for people with or without dementia, there is evidence for multifactorial, individualised community programs. The evidence suggests these interventions do not result in greater mortality and hence are safe. Minimal, single focus interventions will not achieve the targeted outcomes. Trial registration PROSPERO Registration CRD42016050086

Evaluation of the Antimicrobial Activity of American Cockroach (Periplaneta americana) Ethanolic Tissue Extract against Selected Enteric Pathogens

Gastrointestinal (GI) tract infections caused by pathogenic microorganisms have a significant role in the global increase in mortality. This issue sparked an investigation into metabolites derived from numerous organisms that may have antimicrobial property against bacterial infections. The Kirby-Bauer Disc Diffusion method was used to test the extract of the American cockroach (Periplaneta americana) against enteric bacteria. The results indicate that the ethanolic extract of P. americana exhibited antimicrobial activity against the test pathogens, with the greatest inhibitory activity against Vibrio parahaemolyticus (p = 0.00013) and Candida albicans (p = 0.000911), when compared to the antibiotic controls Rifampicin, Trimethoprim, Ofloxacin, Penicillin, and antifungal drug Nystatin. However, there was no evidence of inhibitory activity against Enterococcus faecalis, Salmonella enteritidis, and Serratia marcescens. Thus, the current findings indicate that P. americana tissue extract may have antibacterial activity against medically important pathogens

Evaluation of the Antimicrobial Activity of American Cockroach (Periplaneta americana) Ethanolic Tissue Extract against Selected Enteric Pathogens

Gastrointestinal (GI) tract infections caused by pathogenic microorganisms have a significant role in the global increase in mortality. This issue sparked an investigation into metabolites derived from numerous organisms that may have antimicrobial property against bacterial infections. The Kirby-Bauer Disc Diffusion method was used to test the extract of the American cockroach (Periplaneta americana) against enteric bacteria. The results indicate that the ethanolic extract of P. americana exhibited antimicrobial activity against the test pathogens, with the greatest inhibitory activity against Vibrio parahaemolyticus (p = 0.00013) and Candida albicans (p = 0.000911), when compared to the antibiotic controls Rifampicin, Trimethoprim, Ofloxacin, Penicillin, and antifungal drug Nystatin. However, there was no evidence of inhibitory activity against Enterococcus faecalis, Salmonella enteritidis, and Serratia marcescens. Thus, the current findings indicate that P. americana tissue extract may have antibacterial activity against medically important pathogens

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Reporting of Methodologic Information on Trial Registries for Quality Assessment: A Study of Trial Records Retrieved from the WHO Search Portal

Background: Although randomized clinical trials (RCTs) are considered the gold standard of evidence, their reporting is often suboptimal. Trial registries have the potential to contribute important methodologic information for critical appraisal of study results. Methods and Findings: The objective of the study was to evaluate the reporting of key methodologic study characteristics in trial registries. We identified a random sample (n = 265) of actively recruiting RCTs using the World Health Organization International Clinical Trials Registry Platform (ICTRP) search portal in 2008. We assessed the reporting of relevant domains from the Cochrane Collaboration’s ‘Risk of bias’ tool and other key methodological aspects. Our primary outcomes were the proportion of registry records with adequate reporting of random sequence generation, allocation concealment, blinding, and trial outcomes. Two reviewers independently assessed each record. Weighted overall proportions in the ICTRP search portal for adequate reporting of sequence generation, allocation concealment, blinding (including and excluding open label RCT) and primary outcomes were 5.7% (95% CI 3.0–8.4%), 1.4% (0–2.8%), 41% (35–47%), 8.4% (4.1–13%), and 66% (60–72%), respectively. The proportion of adequately reported RCTs was higher for registries that used specific methodological fields for describing methods of randomization and allocation concealment compared to registries that did not. Concerning other key methodological aspects, weighted overall proportions of RCTs with adequately reported items were as follows: eligibility criteria (81%), secondary outcomes (46%), harm (5%) follow-up duration (62%), description of the interventions (53%) and sample size calculation (1%). Conclusions: Trial registries currently contain limited methodologic information about registered RCTs. In order to permit adequate critical appraisal of trial results reported in journals and registries, trial registries should consider requesting details on key RCT methods to complement journal publications. Full protocols remain the most comprehensive source of methodologic information and should be made publicly available

Epidermal RAF prevents allergic skin disease

The RAS pathway is central to epidermal homeostasis, and its activation in tumors or in Rasopathies correlates with hyperproliferation. Downstream of RAS, RAF kinases are actionable targets regulating keratinocyte turnover; however, chemical RAF inhibitors paradoxically activate the pathway, promoting epidermal proliferation. We generated mice with compound epidermis restricted BRAF/RAF1 ablation. In these animals, transient barrier defects and production of chemokines and Th2-type cytokines by keratinocytes cause a disease akin to human atopic dermatitis, characterized by IgE responses and local and systemic inflammation. Mechanistically, BRAF and RAF1 operate independently to balance MAPK signaling: BRAF promotes ERK activation, while RAF1 dims stress kinase activation. In vivo, JNK inhibition prevents disease onset, while MEK/ERK inhibition in mice lacking epidermal RAF1 phenocopies it. These results support a primary role of keratinocytes in the pathogenesis of atopic dermatitis, and the animals lacking BRAF and RAF1 in the epidermis represent a useful model for this disease