Patient characteristics as effect modifiers for psoriasis biologic treatment response: an assessment using network meta-analysis subgroups

Background: Network meta-analyses (NMAs) of psoriasis treatments, undertaken as part of the NICE Single Technology Appraisal (STA) process, have included heterogeneous studies. When there is inconsistency or heterogeneity across the different comparisons or trials within the network of studies, the results of the NMA may not be valid. We explored the impact of including studies with heterogeneous patient characteristics on the results of NMAs of psoriasis treatments. Methods: All NMAs undertaken for psoriasis STAs were identified and the included studies tabulated, including patient characteristics that may influence relative treatment effects. In addition to the original network of all studies using licensed treatment doses, a range of smaller, less heterogeneous networks were mapped: ‘no previous biologic use’ (<25% patients had prior biologic therapy exposure), ‘Psoriasis Area and Severity Index score ≤25’, ‘weight ≤90 kg’ and ‘white ethnicity’ (≥90% patients were white). Results: Sixty-nine studies were included in our synthesis (34,924 participants). A random effects model with a log-normal prior distribution was chosen for each of the subgroup NMAs. Heterogeneity was reduced for the four smaller networks. There were no significant differences in the relative treatment effect (PASI 75 response) for each treatment across the five NMAs, with all credible intervals overlapping, although there were noticeable differences. Treatment rankings based on the median relative risks were also generally consistent across the networks. However, the NMA that included only studies in which <25% patients had prior biologic therapy exposure had slightly different treatment rankings; the anti-TNF therapies certolizumab pegol and infliximab ranked higher in this network than any other network, although credible intervals were large. Conclusions: This work has highlighted potential differences in treatment response for biologic-naïve patients. When conducting NMAs in any area, heterogeneity in patient characteristics of included trials should be carefully assessed and effect modification related to certain patient characteristics investigated through clinically relevant subgroup analyses

Mathematical Creativity: The Unexpected Links

Creativity in mathematics is identified in many forms or we can say is made up of many components. One of these components is The Unexpected Links where one tries to solve a mathematical problem in a nontraditional manner that requires the formation of hidden bridges between distinct mathematical domains or even between seemingly far ideas within the same domain. In this article, we design problems that express unexpected links in mathematics and suit students of intermediate and secondary levels. We prove their feasibility through teachers’ testimonies and through introducing them in classrooms and collecting students’ attitudes with respect to understanding and interest. Results confirm that students can sense such component and that designed problems had caught teachers’ and students’ interest

The Renewable Energy Consumption-Environmental Degradation Nexus in Top-10 Polluted Countries: Fresh Insights from Quantile-on-Quantile Regression Approach

This empirical examination explored the link between renewable energy utilization and environmental degradation in top-10 polluted countries by using monthly data from 1990-2017. The Quantile-on-Quantile regression (QQ) proposed by Sim and Zhou (2015) and Granger causality in quantiles developed by Troster (2018) are applied. In particular, we examine in what manners, quantiles of renewable energy consumption affect the quantiles of environmental degradation. Our empirical findings unfold overall dependence between renewable energy consumption and ecological deterioration. The findings recommend the presence of a significant negative association between renewable energy consumption and environmental degradation in China, USA, Japan, Canada, Brazil, South Korea and Germany, predominantly in high and low tails but results are totally contrasting in the case of India, Russia and Indonesia. Furthermore, the outcomes of Granger-causality in quantiles conclude a bidirectional causal link between renewable energy consumption and environmental degradation. The empirical findings suggest that governments should need to subsidize green energy in declining ecological degradation

توجهات القيادة الملهمة لتبني برامج الهندسة البشرية لمعالجة التهكم الوظيفي دراسة تحليلية لآراء عينة من العاملين في دائرة صحة نينوى

يهدف البحث الحالي إلى توضيح توجهات القيادة الملهمة لتبني برامج الهندسة البشرية لمعالجة التهكم الوظيفي في دائرة صحة نينوى، ومن اجل تحقيق هدف البحث تم تصميم مخطط فرضي يوضح طبيعة العلاقة بين متغيرات البحث الحالية، كما واعتمدت البحث على المنهج الوصفي التحليلي. وكان السؤال الرئيس للدراسة الحالية هو هل هناك دور للقيادات الملهمة في المديرية قيد البحث لمعالجة التهكم الوظيفي عن طريق تبنيها برامج الهندسة البشرية؟ ولغرض اختبار فرضيات البحث تم تطبيق البحث على عينة من الأفراد العاملين في (دائرة صحة نينوى) للحصول على المعلومات المطلوبة اعتمد الباحثان على استمارة (الاستبانة) التي أعدت لهذا الغرض، إذ كان مجتمع البحث مكون من (410) فرد تم اختيارهم بصفة عشوائية، سحبت منه عينة بلغ حجمها (350) فرداً يمثلون شريحة العاملين في دائرة صحة نينوى من مسؤولي الشعب والوحدات والمنتسبين الاداريين. توصل البحث لنتائج عدة بنيت على أساسها مجموعة من الاستنتاجات (يوجد علاقة ارتباط وتأثير مباشر وغير مباشر ذات دلالة إحصائية ايجابية بين متغير القيادة الملهمة وبرامج الهندسة البشرية في معالجة التهكم الوظيفي) وأهم المقترحات (ينبغي على المنظمة قيد البحث زيادة الاهتمام بإظهار سمات القيادة الملهمة وبرامج الهندسة البشرية)

Attitude of overseas Pakistani students towards modular examination.

oai:mmcedupk_jmmcfinal.jmmc.mmc.edu.pk:article/8Introduction: Modularization an innovative initiative taken by educational institutes around the globe to increase the student’s productivity and efficiency. &nbsp; Objective: The objective of this study was to determine the knowledge and attitude regarding modularization in overseas Pakistani students. Methodology: A cross sectional survey was conducted at the International Medical College of one of the public sector university during December 2012 till February 2014. A total of 425 undergraduate students were approached through non-probability convenience sampling technique and requested to fill a semi structured questionnaire after taking written consent. Result: According to the outset of this paper a total of 425 students were questioned. Among the total 189 students were male (44.47%) and 236 were female (55.52%) out of which the majority belonged from North America/Canada (79.06%). A vast percentage (48.94) invested of about 2 hours of study daily. 63.06% of students believed modular examination to be a fair system and 32.94% of students thought it to be a failure to affect any educational standards. 36% of students blame stress/load for their poor result and 31.06% agrees with the lengthy syllabus being responsible for their down showing GPA’s. 43.06% of students face hardships because of irregular attendance. The major complaint of students (39%) was their teaching style. 46.12% of students prefer to study from lecture notes. Thus, this study completely clears all the aspects of student’s performance in modular system of examinations and its flow and shortcomings. It is important that more effort should be put into cater to student’s stress, loads and make it an effective system to improve a student’s capability and efficiency. &nbsp;Conclusion: The findings of this study can guide us to revise and reshape the assessment system practiced at various medical colleges in Karachi

Psychometric evaluation of Persian version of Diabetes Acceptance Scale (DAS)

Background: Acceptance of diabetes is a psychological adaptation to the potential limitations of the disease. Poor acceptance of diabetes impairs efective self-management of diabetes, leading to worsening metabolic control. This study aimed at determining the psychometric properties of the Persian version of the Diabetes Acceptance Scale. Methods: This cross-sectional methodological study was performed on diabetic patients in Iran in 2021. The ques tionnaire consisted of two parts: demographic characteristics and Diabetes Acceptance Scale. The questionnaire was translated into Persian through the forward–backward translation method. The face validity and content validity were performed qualitatively and quantitatively. Exploratory (n=200) and confrmatory (n=200) factor analysis were performed to evaluate the validity of the structure. Internal consistency and temporal stability were estimated to determine reliability. Results: Exploratory factor analysis on the polychoric correlation matrix obtained three factors: Rational dealing, Resentment and Avoidance, which explained 68.8% of the total DAS variance. Confrmatory factor analysis showed that the 3-fractor model had a good ft to a second independent data set. Finally, Ordinal Cronbach’s alpha coefcient was 0.96, 0.94 and 0.93, respectively for the Rational dealing, Resentment, and Avoidance factor. Also, using intraclass correlation coefcient, the stability of the instrument was 0.97. Conclusion: Based on the fndings of this study, the Persian version of DAS has sufcient validity and reliability to measure the admission of Iranian diabetic patientsinfo:eu-repo/semantics/publishedVersio

Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants

BACKGROUND: Dietary supplementation with prebiotic oligosaccharides to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or very low birth weight (VLBW) infants. OBJECTIVES: To assess the benefits and harms of enteral supplementation with prebiotics (versus placebo or no treatment) for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care database and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to July 2022. We searched clinical trials databases and conference proceedings, and examined the reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing prebiotics with placebo or no prebiotics in very preterm ( 48 hours after birth) invasive infection, duration of hospitalisation, and neurodevelopmental impairment. We used the GRADE approach to assess the level of certainty of the evidence. MAIN RESULTS: We included seven trials in which a total of 705 infants participated. All the trials were small (mean sample size 100). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were potential sources of bias in three of the trials. The studied prebiotics were fructo- and galacto-oligosaccharides, inulin, and lactulose, typically administered daily with enteral feeds during birth hospitalisation. Meta-analyses of data from seven trials (686 infants) suggest that prebiotics may result in little or no difference in NEC (RR 0.97, 95% CI 0.60 to 1.56; RD none fewer per 1000, 95% CI 50 fewer to 40 more; low-certainty evidence), all-cause mortality (RR 0.43, 95% CI 0.20 to 0.92; 40 per 1000 fewer, 95% CI 70 fewer to none fewer; low-certainty evidence), or late-onset invasive infection (RR 0.79, 95% CI 0.60 to 1.06; 50 per 1000 fewer, 95% CI 100 fewer to 10 more; low-certainty evidence) prior to hospital discharge. The certainty of this evidence is low because of concerns about the risk of bias in some trials and the imprecision of the effect size estimates. The data available from one trial provided only very low-certainty evidence about the effect of prebiotics on measures of neurodevelopmental impairment (Bayley Scales of Infant Development (BSID) Mental Development Index score < 85: RR 0.84, 95% CI 0.25 to 2.90; very low-certainty evidence; BSID Psychomotor Development Index score < 85: RR 0.24, 95% 0.03 to 2.00; very low-certainty evidence; cerebral palsy: RR 0.35, 95% CI 0.01 to 8.35; very low-certainty evidence). AUTHORS' CONCLUSIONS: The available trial data provide low-certainty evidence about the effects of prebiotics on the risk of NEC, all-cause mortality before discharge, and invasive infection, and very low-certainty evidence about the effect on neurodevelopmental impairment for very preterm or VLBW infants. Our confidence in the effect estimates is limited; the true effects may be substantially different. Large, high-quality trials are needed to provide evidence of sufficient validity to inform policy and practice decisions

Evaluating progestogens for prevention of preterm birth international collaborative (EPPPIC) individual participant data (IPD) meta-analysis : protocol

BACKGROUND: Preterm birth is the most common cause of death and harm to newborn babies. Babies that are born early may have difficulties at birth and experience health problems during early childhood. Despite extensive study, there is still uncertainty about the effectiveness of progestogen (medications that are similar to the natural hormone progesterone) in preventing or delaying preterm birth, and in improving birth outcomes. The Evaluating Progestogen for Prevention of Preterm birth International Collaborative (EPPPIC) project aims to reduce uncertainty about the specific conditions in which progestogen may (or may not) be effective in preventing or delaying preterm birth and improving birth outcomes. METHODS: The design of the study involves international collaborative individual participant data meta-analysis comprising systematic review, re-analysis, and synthesis of trial datasets. Inclusion criteria are as follows: randomized controlled trials comparing progestogen versus placebo or non-intervention, or comparing different types of progestogen, in asymptomatic women at risk of preterm birth. Main outcomes are as follows; fetal/infant death, preterm birth or fetal death (<=37 weeks, <=34 weeks, <= 28 weeks), serious neonatal complications or fetal/infant death, neurosensory disability (measured at 18 months or later) or infant/child death, important maternal morbidity, or maternal death. In statistical methods, IPD will be synthesized across trials using meta-analysis. Both 'two-stage' models (where effect estimates are calculated for each trial and subsequently pooled in a meta-analysis) and 'one-stage' models (where all IPD from all trials are analyzed in one step, while accounting for the clustering of participants within trials) will be used. If sufficient suitable data are available, a network meta-analysis will compare all types of progesterone and routes of administration extending the one-stage models to include multiple treatment arms. DISCUSSION: EPPPIC is an international collaborative project being conducted by the forming EPPPIC group, which includes trial investigators, an international secretariat, and the research project team. Results, which are intended to contribute to improvements in maternal and child health, are expected to be publicly available in mid 2018. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017068299

The effectiveness of ablative and non-surgical therapies for early hepatocellular carcinoma: systematic review and network meta-analysis of randomised controlled trials

Background & Aims Non-surgical therapies are frequently used for patients with early or very early hepatocellular carcinoma (HCC). The aim of this systematic review and network meta-analysis (NMA) was to evaluate and compare the effectiveness of ablative and non-surgical therapies for patients with small HCC. Methods Nine databases were searched (March 2021) along with clinical trial registries. Randomised controlled trials (RCTs) of any ablative or non-surgical therapy versus any comparator in patients with HCC ≤ 3cm were eligible. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The effectiveness of therapies was compared using NMA. Threshold analysis was undertaken to identify which NMA results had less robust evidence. Results Thirty-seven eligible RCTs were included (including over 3700 patients). Most were from China (n=17) or Japan (n=7). Sample sizes ranged from 30 to 308 patients. The majority had a high RoB or some RoB concerns. No RCTs were identified for some therapies and no RCTs reported quality of life outcomes. The results of the NMA and treatment effectiveness rankings were very uncertain. However, the evidence demonstrated that percutaneous ethanol injection was worse than radiofrequency ablation for overall survival (hazard ratio [HR]: 1.45, 95% credible interval [CrI]: 1.16-1.82), progression-free survival (HR: 1.36, 95% CrI: 1.11-1.67), overall recurrence (relative risk [RR]: 1.19, 95% CrI: 1.02-1.39) and local recurrence (RR: 1.80, 95% CrI: 1.19-2.71). The threshold analysis suggested that robust evidence was lacking for some comparisons. Conclusions It is unclear which treatment is most effective for patients with small HCC because of limitations in the evidence base. It is also not known how these treatments would impact on quality of life. Further high quality RCTs are needed to provide robust evidence but may be difficult to undertake. Funding: National Institute for Health and Care Research (UK). Registration: PROSPERO CRD42020221357