The Effects of Prenatal Buprenorphine Exposure on the Neurobehavioral Development of the Child

Background: Current guidelines for pregnant women with substance use disorder advise prenatal maintenance of opioid agonist therapy with either buprenorphine or methadone. Despite this rise in prenatal opioid agonist therapy, little is known about the effect of prenatal buprenorphine on the neurobehavioral development of the child. This poses the question: does buprenorphine have a long-lasting effect on the central and peripheral nervous system development and behavior of children who were exposed prenatally? Methods: A comprehensive literature review identified articles relating to prenatal buprenorphine and neurobehavioral outcomes. Article searches were conducted on PubMed and Dynamed. Publications from 2002 through November 2021 were pulled for further analysis since buprenorphine was approved by the Food and Drug Administration for use in 2000. The references of pulled articles were also manually searched. The search was limited to peer-reviewed, full-length articles written in English were considered. All articles assessing buprenorphine-naloxone (Suboxone) were excluded from the review due to possible teratogenic effects of naloxone. Relevant information was summarized and included in the review. The full review of the literature identified human and animal studies to gather current knowledge on the neurobehavioral outcomes of children from birth to 5 years of age exposed to buprenorphine prenatally. Results: The literature review revealed that available studies covered three stages of life: fetal, neonatal/infant, and toddler. Neonatal and infant stages were combined into one category due to studies overlapping these similar ages or using the terms interchangeably. Fetal outcomes showed prenatal buprenorphine-exposed fetuses were more likely to exhibit higher level of fetal heart rate variability that eventually normalized later in gestation; fetal motor activity was consistently lower in buprenorphine-exposed fetuses regardless of gestational age. Exposed neonates were more likely to have a depressed initial ability to self-regulate with poor quality of movement. Infants showed no significant deficiency in neurological development. Studies of exposed toddlers showed various results ranging from no significant deviations from normal neurobehavioral development to significant cognitive and motor underdevelopment. Discussion: Prenatal exposure to buprenorphine has varying results on the development of the child, some of which can have long-term detrimental effects. No general conclusion could be made regarding the overall effect of prenatal buprenorphine exposure on an individual due to the wide range of evidence at the toddler stage. While there are multiple factors to consider when assessing neurobehavioral development, there is significant evidence to show there should be serious consideration for future controlled studies of prenatal buprenorphine exposure, from the neonatal stage to older children and beyond

Determinants of Child Stunting, Wasting, and Underweight: Evidence from 2017 to 2018 Pakistan Demographic and Health Survey

Child malnutrition persists in low-resource countries such as Pakistan, indicating an urgent need for interventions and policies aimed to address this critical population health issue. The World Health Organization Global Target 2025 includes the reduction of malnourishment in the form of stunting, wasting, and low weight. This study aims to examine the prevalence of factors associated with three measures of child malnutrition, i.e., stunting, wasting, and low weight in Pakistan. This study uses a secondary data analysis design based on data from Pakistan Demographic and Health Survey (2017-18) that used a two-stage cluster sampling approach. National level data covering urban and rural areas were used for this study consisting of 4,226 children less than 5 years of age. Univariate and multivariable analyses using logistic regression models were conducted. Over 23% of the children were underweight, 8.0% suffered wasting, and 37.7% were stunted. Children with small size at birth (60 cm) were also less likely to be stunted (AOR, 0.288) and underweight (AOR, 0.538). Children who consumed fresh milk were less likely to be classified as wasted (AOR, 0.524) than those children who did not consume fresh milk. The children in high- and middle-economic status families were less likely to be stunted, underweight, or wasted. Children of mothers who had secondary and higher education were less likely to be stunted (AOR, 0.584) and were less likely to be underweight (AOR, 0.668) than illiterate mothers’ children. Children of working mothers were less likely to be wasted compared to children of nonworking mothers (AOR, 0.287). Maternal BMI is also inversely associated with being underweight because overweight and obese mothers were less likely to have underweight children (AOR, 0.585). Our findings reflect a need to design targeted public health policies and community-based education that emphasize the mother’s education on nutrition health and provide socioeconomic resources that enable mothers to provide dietary needs that prevent malnutrition

Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration

Axotomised retinal ganglion cells (RGCs) die rapidly by apoptosis and fail to regenerate because of the limited availability of neurotrophic factors and a lack of axogenic stimuli. However, we have recently showed that pigment epithelium-derived factor (PEDF) promotes RGC survival and axon regeneration after optic nerve crush injury. PEDF has multiple fragments of the native peptide that are neuroprotective, anti-angiogenic and anti-inflammatory. Here we investigated the neuroprotective and axogenic properties of a fragment of PEDF, PEDF-34, in retinal neurons in vitro and when delivered by intravitreal injection and eye drops in vivo. We found that PEDF-34 was 43% more neuroprotective and 52% more neuritogenic than PEDF-44 in vitro. Moreover, in vivo, intravitreal delivery of 1.88 nM PEDF-34 was 71% RGC neuroprotective at 21 days after optic nerve crush compared to intact controls, whilst daily eye drops containing 1.88 nM PEDF-34 promoted 87% RGC survival. After topical eye drop delivery, PEDF-34 was detected in the vitreous body within 30 min and attained physiologically relevant concentrations in the retina by 4 h peaking at 1.4 ± 0.05 nM by 14 days. In eye drop- compared to intravitreal-treated PEDF-34 animals, 55% more RGC axons regenerated 250 μm beyond the optic nerve lesion. We conclude that daily topical eye drop application of PEDF-34 is superior to weekly intravitreal injections in promoting RGC survival and axon regeneration through both direct effects on retinal neurons and indirect effects on other retinal cells

Ultrasonography Determination of Renal Stones with Flank Pain Among Children at Radiology Department of Children Hospital Lahore, Pakistan

Background : In children kidney stones are a standout amongst the majority widely recognized persistent kidney disease in kids. The most widely recognized indication of urolithiasis is stomach ache, in adult plainly particular as colicky ache, in babies and kids. Radiographic assessment of a patient through flank ache analyzes the reason for the ache. Ultrasonography (US) can recognize 90% of stones present in the kidney. Objective:  To evaluate the ultrasonography determination of renal stones with flank pain among children. Place And Duration: The duration of stud was from 01 March to 01 September 2019 at Children Hospital Lahore, Pakistan. Method And Meterial : A cross sectional observational study was included 140 patient’s coming for abdominal and KUB ultrasonography to radiology department of Children Hospital, Lahore. The patients were chosen through convenient sampling technique. All the examined patients including men and women among kids of age ranging from 1 to 16 years. Results: Overall 140 patients are included in this research. Out of 140 patients men were 92(65.7%) and women were 48(34.3%) in this study population. In 140 patients, 47(33.6%) were identified with kidney stones and 93(66.4%) were recognized without kidney stones. Out of 140 individuals 76(54.3%) patients contained ache and in 48(34.3%) pain is radiating the remaining 16(11.4%) had no pain. Conclusion: Ultrasonography is extremely helpful in the evaluation of nephrolithiasis with flank ache amongst children

Review of Progress and Prospects in Research on Enzymatic and Non- Enzymatic Biofuel Cells; Specific Emphasis on 2D Nanomaterials

Energy generation from renewable sources and effective management are two critical challenges for sustainable development. Biofuel Cells (BFCs) provide an elegant solution by combining these two tasks. BFCs are defined by the catalyst used in the fuel cell and can directly generate electricity from biological substances. Various nontoxic chemical fuels, such as glucose, lactate, urate, alcohol, amines, starch, and fructose, can be used in BFCs and have specific components to oxide fuels. Widely available fuel sources and moderate operational conditions make them promise in renewable energy generation, remote device power sources, etc. Enzymatic biofuel cells (EBFCs) use enzymes as a catalyst to oxidize the fuel rather than precious metals. The shortcoming of the EBFCs system leads to integrated miniaturization issues, lower power density, poor operational stability, lower voltage output, lower energy density, inadequate durability, instability in the long-term application, and incomplete fuel oxidation. This necessitates the development of non-enzymatic biofuel cells (NEBFCs). The review paper extensively studies NEBFCs and its various synthetic strategies and catalytic characteristics. This paper reviews the use of nanocomposites as biocatalysts in biofuel cells and the principle of biofuel cells as well as their construction elements. This review briefly presents recent technologies developed to improve the biocatalytic properties, biocompatibility, biodegradability, implantability, and mechanical flexibility of BFCs.This work was supported by the Qatar National Research Fund (a member of Qatar Foundation) under UREP grant #UREP28-052-2-020. The statements made herein are solely the responsibility of the authors

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18 : a geospatial modelling study

Background More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels.Methods We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km x 5 km resolution in 98 LMICs based on 2.1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution.Findings Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205000 (95% uncertainty interval 147000-257000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution.Interpretation Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic