Background: The World Health Organization (WHO) defines perinatal mortality (PNM) as the "death of a baby between 28 weeks of gestation onwards till the first 7 days of life." PNM is a key indicator of the quality of care for newborns and directly reflects the category of prenatal, intrapartum, and postpartum care given to a newborn. According to a report published by the WHO, 2.3 million children died within their first 20 days of life in 2022. Approximately 6500 newborn deaths occur every day, accounting for 47% of all child deaths under the age of five years. PNM is a public health concern in low and middle-income countries. According to the Pakistan Health and Demographic Survey 2017-18, the PNM rate has remained consistently high in Pakistan (75 per 1000 births) during the last decade. Aims: To observe the frequency of PNM and early neonatal mortality (ENM) among the Pakistani population within the last decade and to identify additional risk factors for PNM and ENM. Methods: Published studies were searched using keywords comprising PNM, ENM, stillbirths, risk rate, perinatal period, and their combinations with search engines such as Science Direct, SCOPUS, PubMed, and Google Scholar. We followed Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) guidelines to filter articles and selected 18 relevant articles for systematic review. All studies reported either the PNM, ENM, stillbirth, or live birth rate. Results: Systematic review showed that the PNM rate in Pakistan remained high from 2013 to 2022. Hypertensive disorders, antepartum hemorrhage, and neonatal infections increased the overall risk of PNM and ENM. Other factors that contributed to the high PNM rate were advanced maternal age, low birth weight, congenital abnormalities, multigravida, poor socioeconomic conditions, and other medical problems such as gestational diabetes. Conclusion: The PNM rate in Pakistan was found to be high according to the systematic review, but discrepancies were observed when compared with the WHO figures for PNM. We recommend conducting more original research to accurately assess the PNM rate in Pakistan, which is essential for informed and effective policy making.

Objectives: This systematic review (SR) highlights principles for nutrient clinical trials and explore the diverse physiological functions of vitamin D beyond its traditional role in the musculoskeletal system related to clinical study designs. Background: Thousands of published research articles have investigated the benefits of vitamin D (a nutrient example taken in this SR) beyond the musculoskeletal system, including the immune, pulmonary, and cardiovascular systems; pregnancy; autoimmune disorders; and cancer. They illustrated vitamin D's molecular mechanisms, interactions, and genomic and nongenomic actions. Methods: This SR was designed to identify shortcomings in clinical study designs, statistical methods, and data interpretation that led to inconsistent findings in vitamin D-related publications. SR also highlights examples and insights into avoiding study design errors in future clinical studies, including randomized controlled clinical trials (RCTs). The SR adheres to the latest PRISMA statement, guidelines, and the PICOS process. Results: Inappropriate or flawed study designs were frequent in clinical trials. Major failures discussed here include too short clinical study duration, inadequate or infrequent doses, insufficient statistical power, failure to measure baseline and achieved levels, and recruiting vitamin D-sufficient participants. These design errors have led to misleading interpretations. Thus, conclusions from such studies should not be generalized or used in guidelines, recommendations, or policymaking. Conclusion: Adequately powered epidemiological studies and RCTs with sufficient vitamin D and duration in individuals with vitamin D deficiency reported favorable clinical outcomes, enriching the literature, enabling to understand its physiology and mechanisms. Proper study designs with rigorous methodologies and cautious interpretation of outcomes are crucial in advancing the nutrient field. The principles discussed apply not only to vitamin D, but also other micro-nutrients and nutraceutical research. Adhering to them enhances the credibility and reliability of clinical trials, SRs, and meta-analysis outcomes. The study emphasizes the importance of focused, hypothesis-driven, well-designed, statistically powered RCTs to explore the diverse benefits of nutrients, conducted in index nutrient deficient participants, and avoidance of study design errors. Findings from such studies should be incorporated into clinical practice, policymaking, and public health guidelines, improving the health of the nation and reducing healthcare costs.

Greenhouse gas (GHG) emissions are creating unprecedented climate-driven extreme weather, with levels of heat and humidity surpassing human physiological tolerance for heat stress. These conditions create a risk of mass casualties, with some populations particularly vulnerable due to physiological, behavioural and socioeconomic conditions (eg, lack of adequate shelter, limited healthcare infrastructure, sparse air conditioning access and electrical grid vulnerabilities). Children, especially young children, are uniquely vulnerable to extreme heat-related morbidity and mortality due to factors including low body mass, high metabolism, suboptimal thermoregulatory mechanisms and behavioural vulnerabilities. Children are also uniquely vulnerable to non-fatal heat-related morbidities, including malnutrition due to agricultural disruptions and cardiometabolic, respiratory and mental illnesses from heat exposure and/or confinement during heat avoidance. Climate mitigation through GHG reductions is central to reducing harms to children and preventing the loss of a generation to climate change. In regions most predisposed to extreme heat-driven mass casualties under various GHG emission scenarios-particularly South Asian and Southwest Asian and North African regions-adaptation tools specific to children's needs are the most urgently needed. Existing public health interventions (eg, cooling infrastructure and preventative educational campaigns) to reduce acute heat mortality, and medical infrastructure capacity to treat heat-related illnesses are currently inadequate to meet children's growing heat resiliency needs. Paediatricians and other clinical and community child healthcare providers in these regions lack education about children's heat risks and adaptation tools. Paediatricians and other child healthcare providers have a crucial role in research, education, clinical practice and advocacy to protect children during extreme heat events. Paediatricians, other child healthcare providers and stakeholders of children's well-being are urged to act on young children's behalf and to elevate youth leadership in GHG mitigation and extreme heat adaptation policy-making.

Effective diabetes management can prevent avoidable diabetes-related hospitalizations. This review examines the impact of financial incentives for diabetes management in primary care settings on diabetes-related hospitalizations, hospitalization costs, and premature mortality. To assess the evidence, we conducted a literature search of studies using five databases: Medline, Embase, Scopus, CINAHL and Web of Science. We examined the results by health insurance system, study quality or diabetes population (newly diagnosed diabetes). We identified 32 articles ranging from fair- to high-quality: 19 articles assessed the relationship between financial incentives for diabetes management and hospitalizations, 8 assessed hospitalization costs, and 15 assessed mortality. Many studies found that financial incentives for diabetes management reduced hospitalizations, while a few found no effects. Similar findings were evident for hospitalization costs and mortality. The results did not differ by the type of health insurance system, but the quality of the studies did matter; most high-quality studies reported reduced hospitalizations and/or mortality. We also found that financial incentives tend to be beneficial for patients with newly diagnosed diabetes. We conclude that well-designed diabetes management incentives can reduce diabetes-related hospitalizations, especially for newly diagnosed diabetes patients.

Objectives: (i) To analyze trends and gaps in evidence of health effects on pollutants and extreme temperatures by evidence mapping; (ii) to conduct a cross-sectional survey on the use of the Grades of Recommendations Assessment Development and Evaluation (GRADE) in systematic reviews or meta-analyses (SR/MAs) of health effects on pollutants and extreme temperatures. Study Design and Setting: PubMed, Embase, the Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched until July 7, 2022. SR/MAs investigated health effects of pollutants and extreme temperatures were included.Results: Out of 22,658 studies, 312 SR/MAs were included in evidence mapping, and the effects of pollutants on cancer and congenital malformations were new research hotspots. Among 16 SR/MAs involving 108 outcomes that were rated using GRADE, the certainty of evidence was mostly downgraded for inconsistency (50, 42.7%), imprecision (33, 28.2%), and risk of bias (24, 20.5%). In contrast, concentration-response gradient (26, 65.0%) was the main upgrade factor.Conclusion: GRADE is not widely used in SR/MAs of health effects on pollutants and extreme temperatures. The certainty of evidence is generally low, mainly because of the serious inconsistency or imprecision. Use of the GRADE in SR/MAs of health effects on pollutants and extreme temperatures should strengthen.& COPY; 2023 Elsevier Inc. All rights reserved.

Background: Metabolic syndrome has been linked to an increased risk of colorectal cancer (CRC) incidence and mortality, but whether adopting a healthy lifestyle could attenuate the risk of CRC conferred by metabolic syndrome remains unclear. The aim of the study is to investigate the individual and joint effects of modifiable healthy lifestyle and metabolic health status on CRC incidence and mortality in the UK population. Methods: This prospective study included 328,236 individuals from the UK Biobank. An overall metabolic health status was assessed at baseline and categorized based on the presence or absence of metabolic syndrome. We estimated the association of the healthy lifestyle score (derived from 4 modifiable behaviors: smoking, alcohol consumption, diet, physical activity and categorized into "favorable," "intermediate", and "unfavorable") with CRC incidence and mortality, stratified by metabolic health status. Results: During a median follow-up of 12.5 years, 3,852 CRC incidences and 1,076 deaths from CRC were newly identified. The risk of incident CRC and its mortality increased with the number of abnormal metabolic factors and decreased with healthy lifestyle score (P trend = 0.000). MetS was associated with greater CRC incidence (HR = 1.24, 95% CI: 1.16 - 1.33) and mortality (HR = 1.24, 95% CI: 1.08 - 1.41) when compared with those without MetS. An unfavorable lifestyle was associated with an increased risk (HR = 1.25, 95% CI: 1.15 - 1.36) and mortality (HR = 1.36, 95% CI: 1.16 - 1.59) of CRC across all metabolic health status. Participants adopting an unfavorable lifestyle with MetS had a higher risk (HR = 1.56, 95% CI: 1.38 - 1.76) and mortality (HR = 1.75, 95% CI: 1.40 - 2.20) than those adopting a favorable healthy lifestyle without MetS. Conclusion: This study indicated that adherence to a healthy lifestyle could substantially reduce the burden of CRC regardless of the metabolic status. Behavioral lifestyle changes should be encouraged for CRC prevention even in participants with MetS.

Aim To compare the safety and effects of unrestricted visiting policies (UVPs) and restricted visiting policies (RVPs) in intensive care units (ICUs) with respect to outcomes related to delirium, infection, and mortality. Methods MEDLINE, Cochrane Library, Embase, Web of Science, CINAHL, CBMdisc, CNKI, Wanfang, and VIP database records generated from their inception to 22 January 2022 were searched. Randomized controlled trials and quasi-experimental studies were included. The main outcomes investigated were delirium, ICU-acquired infection, ICU mortality, and length of ICU stay. Two reviewers independently screened studies, extracted data, and assessed risks of bias. Random-effects and fixed-effects meta-analyses were conducted to obtain pooled estimates, due to heterogeneity. Meta-analyses were performed using RevMan 5.3 software. The results were analyzed using odds ratios (ORs), 95% confidence intervals (CIs), and standardized mean differences (SMDs). Results Eleven studies including a total of 3741 patients that compared UVPs and RVPs in ICUs were included in the analyses. Random effects modeling indicated that UVPs were associated with a reduced incidence of delirium (OR = 0.4, 95% CI 0.25-0.63, I-2 = 71%, p = 0.0005). Fixed-effects modeling indicated that UVPs did not increase the incidences of ICU-acquired infections, including ventilator-associated pneumonia (OR = 0.96, 95% CI 0.71-1.30, I-2 = 0%, p = 0.49), catheter-associated urinary tract infection (OR 0.97, 95% CI 0.52-1.80, I-2 = 0%, p = 0.55), and catheter-related blood stream infection (OR = 1.15, 95% CI 0.72-1.84, I-2 = 0%, p = 0.66), or ICU mortality (OR = 1.03, 95% CI 0.83-1.28, I-2 = 49%, p = 0.12). Forest plotting indicated that UVPs could reduce the lengths of ICU stays (SMD = - 0.97, 95% CI - 1.61 to 0.32, p = 0.003). Conclusion The current meta-analysis indicates that adopting a UVP may significantly reduce the incidence of delirium in ICU patients, without increasing the risks of ICU-acquired infection or mortality. Further large-scale, multicenter studies are needed to confirm these indications.

Sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and 100% fruit juices are frequently consumed and have been documented that they could lead to serious disease burden. However, inconsistent evidence on the association between SSBs, ASBs, and 100% fruit juices consumption and mortality have been presented. PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and PsycINFO were systematically searched. We conducted a random-effects meta-analysis and dose-response meta-analysis to assess the association and calculated the pooled hazard ratio with 95% confidence interval. And we evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Thirteen studies with 1,539,127 participants proved eligible. An SSB-consumption increase per 250 mL/day was associated with a 4% greater risk of all-cause mortality (5 more per 1000 persons; low certainty) and 8% greater risk of cardiovascular disease mortality (3 more per 1000 persons; low certainty). ASB-consumption increase per 250 mL/day demonstrated a 4% greater risk of all-cause mortality (5 more per 1000 persons; low certainty) and 4% greater risk of cardiovascular disease mortality (2 more per 1000 persons; low certainty). The association of SSBs and ASBs with cancer mortality was not significant, with a very low certainty of evidence. There was evidence of a linear dose-response association between SSB intake and cancer mortality, as well as between ASB intake and all-cause mortality and cancer mortality. We observed a non-linear dose-response association between ASB intake and CVD mortality and SSB intake and all-cause and CVD mortality. Low certainty of evidence demonstrated that per 250 mL/day consumption increase in SSBs and ASBs had a small impact on all-cause and cardiovascular disease mortality but not on cancer mortality. The association of 100% fruit juice consumption with all-cause and cardiovascular disease mortality was uncertain.

Growing evidence indicates that insomnia may be associated with mortality. However, these findings have been inconsistent. We systematically searched MEDLINE and EMBASE to identify prospective cohort studies that assessed the association between insomnia disorder/individual insomnia symptoms and the risk of mortality among adults aged ≥18 yrs. We addressed this association using summary hazard ratios (HRs) and 95% confidence intervals (CIs) calculated using random-effects meta-analysis, and the GRADE approach to rate the certainty of evidence. Twenty-nine cohorts including 1,598,628 individuals (55.3% men; mean age 63.7 yrs old) with a median follow-up duration of 10.5 yrs proved eligible. Difficulty falling asleep (DFA) and non-restorative sleep (NRS) were associated with an increased risk of all-cause mortality (DFA: HR = 1.13, 95%CI 1.03 to 1.23, p = 0.009, moderate certainty; NRS: HR = 1.23, 95%CI 1.07 to 1.42, p = 0.003, high certainty) and cardiovascular disease mortality (DFA: 1.20, 95%CI: 1.01, 1.43; p = 0.04, moderate certainty; NRS: HR = 1.48, 95%CI 1.06 to 2.06, p = 0.02, moderate certainty). Convincing associations between DFA and all-cause mortality were restricted to the mid to older-aged population (moderate credibility). Insomnia disorder, difficulty maintaining sleep, and early morning awakening proved to be unassociated with all-cause and cardiovascular disease mortality. No insomnia symptoms proved to be associated with cancer-related mortality.

Background: With over 230 million surgical procedures performed annually worldwide, better application of evidence in anesthesia and perioperative medicine may reduce widespread variation in clinical practice and improve patient care. However, a comprehensive summary of the complete available evidence has yet to be conducted. This scoping review aims to map the existing literature investigating perioperative anesthesia interventions and their potential impact on patient mortality, to inform future knowledge translation and ultimately improve perioperative clinical practice. Methods: Searches were conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Library databases from inception to March 2015. Study inclusion criteria were adult patients, surgical procedures requiring anesthesia, perioperative intervention conducted/organized by a professional with training in anesthesia, randomized controlled trials (RCTs), and patient mortality as an outcome. Studies were screened for inclusion, and data was extracted in duplicate by pairs of independent reviewers. Data were extracted, tabulated, and reported thematically. Results: Among the 10,505 publications identified, 369 RCTs (n = 147,326 patients) met the eligibility criteria. While 15 intervention themes were identified, only 7 themes (39 studies) had a significant impact on mortality: pharmacotherapy (n = 23), nutritional (n = 3), transfusion (n = 4), ventilation (n = 5), glucose control (n = 1), medical device (n = 2), and dialysis (n = 1). Conclusions: By mapping intervention themes, this scoping review has identified areas requiring further systematic investigation given their potential value for reducing patient mortality as well as areas where continued investment may not be cost-effective given limited evidence for improving survival. This is a key starting point for future knowledge translation to optimize anesthesia practice.