Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients.

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.

Neonatal magnesium sulphate for neuroprotection: A systematic review and meta-analysis.

AIM: To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE). METHOD: This was a systematic review of randomized controlled trials (RCTs) (with meta-analysis) and non-RCTs assessing magnesium sulphate for treating perinatal asphyxia and HIE at 35 weeks or more gestation (primary outcomes: neonatal death and death or long-term major neurodevelopmental disability). RESULTS: Twenty-five RCTs (2099 infants) and four non-RCTs (871 infants) were included, 23 in low- and middle-income countries (LMICs). In RCTs, reductions in neonatal death with magnesium sulphate versus placebo or no treatment (risk ratio [RR] = 0.68; 95% confidence interval [CI] = 0.53-0.86; 13 RCTs), and magnesium sulphate with melatonin versus melatonin alone (RR = 0.74; 95% CI = 0.58-0.95; one RCT) were observed. No difference in neonatal death was seen for magnesium sulphate with therapeutic hypothermia versus therapeutic hypothermia alone (RR = 0.66, 95% CI = 0.34-1.26; three RCTs), or magnesium sulphate versus phenobarbital (RR = 3.00; 95% CI = 0.86-10.46; one RCT). No reduction in death or long-term neurodevelopmental disability (RR = 0.52; 95% CI = 0.14-1.89; one RCT) but reductions in several short-term adverse outcomes were observed with magnesium sulphate. Evidence was low- to very-low certainty because of risk of bias and imprecision. INTERPRETATION: Given the uncertainty of the current evidence, further robust neonatal magnesium sulphate research is justified. This may include high-quality studies to determine stand-alone effects in LMICs and effects with and after therapeutic hypothermia in high-income countries.

A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment.

BACKGROUND: In total pancreatectomy with islet auto-transplantation, successful diabetes outcomes are limited by islet loss from the instant blood mediated inflammatory response. We hypothesized that blockade of the inflammatory response with either etanercept or alpha-1-antitrypsin would improve islet function and insulin independence. METHODS: We randomized 43 participants to receive A1AT (90 mg/kg x 6 doses, n = 13), or etanercept (50 mg then 25 mg x 5 doses, n = 14), or standard care (n = 16), aiming to reduce detrimental effects of innate inflammation on early islet survival. Islet graft function was assessed using mixed meal tolerance testing, intravenous glucose tolerance testing, glucose-potentiated arginine-induced insulin secretion studies, HbA1c, and insulin dose 3 months and 1 year post-TPIAT. RESULTS: We observed the most robust acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) at 3 months after TPIAT in the etanercept-treated group (p ≤ 0.02), but no differences in other efficacy measures. The groups did not differ overall at 1 year but when adjusted by sex, there was a trend towards a sex-specific treatment effect in females (AIRglu p = 0.05, ACRglu p = 0.06), with insulin secretion measures highest in A1AT-treated females. CONCLUSION: Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment. CLINICAL TRIAL NOTATION: This study was performed under an Investigational New Drug Application (IND #119828) from the Food and Drug Administration and was registered on clinicaltrials.gov (NCT#02713997).

Clinical features associated with epilepsy occurrence, resolution, and drug resistance in children with cerebral palsy: A population-based study.

AIM: To investigate clinicoradiological features associated with epilepsy, its resolution, and drug resistance in children with cerebral palsy (CP). METHOD: Data were gathered from the New South Wales/Australian Capital Territory CP Register, encompassing children with CP born between 2003 and 2015 (n = 1916). Clinical features and the severity of impairments were compared among three groups: children with current epilepsy (n = 604), those with resolved epilepsy by age 5 years (n = 109), and those without epilepsy (n = 1203). Additionally, a subset of the registry cohort attending Children's Hospital Westmead (n = 256) was analysed to compare epilepsy and treatment characteristics between drug-responsive (n = 83) and drug-resistant groups (n = 147) using logistic regression and hierarchical cluster analysis. RESULTS: Manual Ability Classification System levels IV and V, intellectual impairment, and vision impairment were found to be associated with epilepsy in children with CP on multivariable analysis (p < 0.01). Moderate to severe intellectual impairment and bilateral spastic CP were independent positive and negative predictors of epilepsy persistence at the age of 5 years respectively (p < 0.05). Microcephaly and multiple seizure types were predictors of drug-resistant epilepsy (area under the receiver operating characteristic curve of 0.83; 95% confidence interval 0.77-0.9). Children with a known genetic cause (14%) and CP epilepsy surgery group (4.3%) formed specific clinical subgroups in CP epilepsy. INTERPRETATION: Our study highlights important clinical associations of epilepsy, its resolution, and treatment response in children with CP, providing valuable knowledge to aid in counselling families and identifying distinct prognostic groups for effective medical surveillance and optimal treatment.

The Sexual and Reproductive Health of Adolescents with Cerebral Palsy in Rural Bangladesh: A Qualitative Analysis.

Adolescents with disability in the Global South have unique sexual and reproductive health (SHR) experiences and needs; however, they are rarely included in SRH discourse. This qualitative study, conducted in rural Bangladesh, used semi-structured interviews to understand how adolescents with cerebral palsy (CP) experience their SRH. Participants were recruited from the Bangladesh Cerebral Palsy Register and included 24 adolescents with CP (n = 12 female; n = 12 male) and 76 parents (n = 56 mothers, n = 17 fathers, n = 3 other relatives). Data were analyzed using reflexive thematic analysis. Findings highlighted heterogeneity among adolescents with CP including differences for adolescent men versus women. For some adolescent men with CP, sexual maturity was viewed as bringing new opportunities, whereas for other men, adolescence affirmed exclusions and some transgressed sociocultural norms as they struggled to navigate their pubescent body alongside new privacy requirements. For adolescent women with CP, sexual maturity was associated with new domestic responsibilities, silence and secrecy regarding menstruation, and increased vulnerability to sexual violence and abuse. Adolescent men and women with CP spoke about marriage as something "everybody wants," however, was deemed "impossible" for those with more impairment-related support needs. Both adolescent men and women with CP lacked access to SRH information and support. Mothers positioned providing care to their adolescent child with CP after puberty as "shameful." Our findings suggest that disability, health, and education services in rural Bangladesh need to adopt a life-course approach that incorporates the SRH of adolescents with CP. We recommend the provision of SRH education that addresses the physical, cognitive, and social needs of adolescents with CP.

Epidemiology of eye diseases among children with disability in rural Bangladesh: a population-based cohort study.

AIM: To describe the epidemiology of eye diseases among children with disability in rural Bangladesh. METHOD: We established a population-based cohort of children with disability using the key informant method. Children younger than 18 years with disability (i.e. physical, visual, hearing, speech, epilepsy) were included. We used detailed ophthalmological assessments following World Health Organization (WHO) protocols by a multidisciplinary team including an ophthalmologist, optometrist, physician, and physiotherapist. Visual impairment, blindness, and severe visual impairment (SVI) were defined by following WHO categories. RESULTS: Between October 2017 and February 2018, 1274 children were assessed (43.6% female; median [interquartile range] age 9y 10mo [6y -13y 7mo]). Overall, 6.5% (n=83) had blindness/SVI, and 5.6% (n=71) had visual impairment. In the group with blindness/SVI, 47% (n=39) had cortical blindness; of those, 79.5% (n=31) had cerebral palsy (CP). The other main anatomical sites of abnormalities in this group included lens (13.3%, n=11), cornea (10.8%, n=9), and optic nerve (9.6%, n=8). In the group with visual impairment, 90.1% (n=64) had refractive error. Overall, 83.1% (n=69) and 78.8% (n=56) of those with blindness/SVI and visual impairment had avoidable causes. Most children with blindness/SVI and visual impairment lacked access to education. INTERPRETATION: The burden of blindness/SVI/visual impairment is high among children with disability in rural Bangladesh, mostly due to avoidable causes. Overrepresentation of CP and cortical blindness in the group with blindness/SVI and refractive error in the group with visual impairment highlights the need for integration of ophthalmology assessment, eye care, and refraction services in comprehensive health care for children with disability including CP in rural Bangladesh.

Epidemiology of cerebral palsy in Sumba Island, Indonesia.

AIM: To define the epidemiology, clinical characteristics, and rehabilitation status of children with cerebral palsy (CP) in Sumba Island, Indonesia. METHOD: A community-based key informant method survey among children (aged <18y) with CP was conducted between March and August 2017. Children with suspected CP underwent detailed neurodevelopmental assessment by a multidisciplinary medical team. Socio-demographic characteristics, aetiology, motor type, motor severity, associated impairments, educational, and rehabilitation status were documented. RESULTS: There were 130 children with clinically confirmed CP. The mean age at assessment was 8 years 11 months and 43.8% (n=57) of the children were female. The mean age at CP diagnosis was 6 years 5 months. Of these children, 46.9% (n=61) had post-neonatally acquired CP, most frequently because of vaccine-preventable infectious encephalopathy (73.8%, n=45). In total, 80.8% (n=105) had a predominantly spastic motor type of CP and 83.8% (n=109) were classified in Gross Motor Functional Classification System levels III to V. A total of 77.7% (n=101) had at least one associated impairment (speech 77.5%, intellectual 29.2%, visual 13.8%, hearing 20.0%, and epilepsy 13.5%). And 66.2% (n=86) had never received rehabilitation services. INTERPRETATION: Post-neonatally acquired CP was common in this setting. Addressing preventable post-neonatally acquired risk factors for CP should be a public health priority. Earlier identification and diagnosis of CP would also provide new opportunities for early intervention and targeted rehabilitation services.

What predicts the proxy-reported health-related quality of life of adolescents with cerebral palsy in Bangladesh?

BACKGROUND: The health-related quality of life (HRQoL) of adolescents with CP in low and middle-income countries is often poor, as is the case in Bangladesh. This exploratory study examined what factors predict the proxy-reported HRQoL of adolescents with CP in rural Bangladesh, a typical low- and middle-income country (LMIC). METHODS: Adolescents with CP (10 to 18y) were identified using the Bangladesh Cerebral Palsy Register. HRQoL was assessed using the Cerebral Palsy Quality of Life-Teens proxy-report questionnaire (CPQoL-Teens), adolescent mental health using the Strengths and Difficulty Questionnaire (SDQ) and caregiver mental health using the Depression, Anxiety and Stress Scale (DASS-21). Theoretical and statistical interests (i.e. bivariate analysis, p < 0.05) identified potential predictors which were entered into hierarchical multiple linear regression (HMLR) models in order of clinical significance; HMLR related adolescent clinical characteristics, adolescent and caregiver mental health and proxies of socioeconomic status to CPQoL-Teens dimensions. RESULTS: One hundred fifty-four adolescents with CP (mean age 15y 1mo, SD 1y 8mo, female 31.2%) participated in this study. Twenty-four factors were identified to explore for relationship to adolescent proxy-reported HRQoL. Fifteen of the factors correlated to one or more CPQoL-Teens dimension; strongest correlation was between 'feelings about functioning' and motor impairment (r = 0.545). Nine were predictive of CPQoL-Teens dimensions; adolescent sex, school attendance, severity of motor impairment, hearing and speech impairment, mother's education, primary caregiver depression and stress, and having a sanitary latrine at home resulting in score changes of between 0.79 (95% CI 0.24 to 1.35) to 35.1 (95% CI 6.03 to 64.22). CONCLUSIONS: Many of the factors predicting the proxy-reported HRQoL of adolescents with CP are amenable to intervention, and have the potential to improve adolescent wellbeing. Several determinants are priorities of the sustainable development goals (SDGs); these findings should inform resource prioritization to improve the wellbeing of adolescents with CP in Bangladesh and other LMICs.

A quality of life questionnaire for adolescents with cerebral palsy: psychometric properties of the Bengali CPQoL-teens.

BACKGROUND: Quality of life (QoL) and health-related quality of life (HRQoL) measurement in low and middle-income countries of people with cerebral palsy (CP), the major cause of childhood physical disability, is essential to assess the impact of interventions and inform policies that best improve people's lives. The purpose of this study was to cross-culturally translate and psychometrically validate the Cerebral Palsy Quality of Life-Teens (CPQoL-Teens) self- and proxy-report questionnaires for application with adolescents with CP in Bangladesh. METHOD: The CPQoL-Teens questionnaires were translated to Bengali using forward and backwards cross-cultural translation protocols. The questionnaires were interviewer administered to adolescents and their primary caregivers, identified through the Bangladesh Cerebral Palsy Register. Feasibility, sensitivity, internal consistency, content, concurrent and construct validity were assessed. RESULTS: One hundred fifty four adolescents with CP (10 to 18y; mean 15y 1mo SD 1y 8mo; 31.2% female) participated. Feasibility, sensitivity and internal consistency of both self- and proxy-report questionnaires was excellent; nil missing scores except 'school wellbeing' which was associated with non-school attendance (48.4 to 74.7%); floor and ceiling effect ≤13.6%; Cronbach's alpha 0.77 to 0.94. Instrument validity was good; confirmatory factor analysis reflected five of the seven original instrument dimensions. CPQoL-Teens correlated to Kidscreen-27 on most dimensions (r = 0.176 to 0.693, p < 0.05); minimal difference in known groups was observed by mental health status (p < 0.05) although could be accounted for by homogeneity of mental health problems in the sample. CONCLUSION: The CPQoL-Teens self- and proxy report questionnaires successfully translated to Bengali and showed excellent feasibility and strong psychometric properties confirming suitability to assess indicators of HRQoL among adolescents with CP in Bangladesh.

Epidemiology of cerebral palsy in Bangladesh: a population-based surveillance study.

AIM: To examine the prevalence, clinical characteristics, and risk factors of cerebral palsy (CP) in children in Bangladesh. METHOD: The Bangladesh CP Register is an ongoing population-based surveillance database of children with CP from a geographically defined area in Bangladesh. Cases were defined based on Surveillance of CP in Europe and Australian CP Register criteria after clinical assessments and identification by the key informant's method. RESULTS: In total, 726 children with CP were identified between January 2015 and December 2016. Mean age was 7 years 7 months (standard deviation [SD] 4y 6mo; range: 4.8mo-18y; median 7y 1.2mo; 61.8% male, 38.2% female). Mean age at CP diagnosis was 5 years 2 months (SD 3.8). Observed prevalence was 3.4 per 1000 children (95% confidence interval [CI]: 3.2-3.7), resulting in an estimated 233 514 children (95% CI: 219 778-254 118) with CP in Bangladesh. The majority (79.6%) had spastic CP. Altogether, 79.6% of the children with CP had at least one associated impairment (speech 67.6%, intellectual 39.0%, epilepsy 23.7%, visual 10.2%, and hearing 10.2%). In total, 78.2% never received rehabilitation. INTERPRETATION: In Bangladesh, the burden of CP is high, and diagnosis is substantially delayed, limiting opportunities for early intervention. There is a lack of available services and the majority of the children had preventable risk factors. WHAT THIS PAPER ADDS: Prevalence of cerebral palsy (CP) is 3.4 per 1000 children in rural Bangladesh. There are an estimated 233 514 children with CP in Bangladesh. The majority have potentially preventable risk factors. Diagnosis of CP is delayed, limiting opportunities for early intervention. There is a lack of available services for children with CP in rural Bangladesh.

EPIDEMIOLOGÍA DE LA PARÁLISIS CEREBRAL EN BANGLADESH: UN ESTUDIO DE VIGILANCIA BASADO EN LA POBLACIÓN: OBJETIVO: Examinar la prevalencia, las características clínicas y los factores de riesgo de la parálisis cerebral (PC) en niños en Bangladesh. MÉTODO: El Registro de PC (BCPR siglas en ingles) de Bangladesh es una base de datos de vigilancia basada en la población de niños con PC, de un área geográficamente definida, en Bangladesh. Los casos se definieron siguiendo los criterios de vigilancia de PC en Europa y los criterios del registro de PC australiano, teniendo en cuenta las evaluaciones clínicas y la identificación por el método del informante clave. RESULTADOS: En total, se identificaron 726 niños con PC entre enero del 2015 y diciembre del 2016. La edad media fue de 7 años y 7 meses (desviación estándar [DE] 4ª 6m; rango: 4,8m-18a; mediana 7a 1,2m; 61,8% masculino, 38,2 % femenino). La edad promedio en el diagnóstico de PC fue de 5 años y 2 meses (DE 3.8). La prevalencia observada fue de 3,4 por cada 1.000 niños (intervalo de confianza [IC] del 95%: 3,2-3,7), resultando en un número estimado de 233.514 niños con PC (IC del 95% 219 778-254 118) en Bangladesh. La mayoría (79.6%) tenía PC espástica. En total, el 79.6% de los niños con PC tenían al menos un impedimento asociado (habla 67.6%, intelectual 39.0%, epilepsia 23.7%, visual 10.2% y audición 10.2%). En total, el 78.2% nunca recibió rehabilitación. INTERPRETACIÓN: En Bangladesh, el impacto de PC es alto y el diagnóstico se retrasa sustancialmente, lo que limita las oportunidades de intervención temprana. Hay una falta de servicios disponibles y la mayoría de los niños tenían factores de riesgo prevenibles.

EPIDEMIOLOGIA DA PARALISIA CEREBRAL EM BANGLADESH: UM ESTUDO DE VIGILÂNCIA COM BASE POPULACIONAL: OBJETIVO: Examinar a prevalência, características clínicas, e fatores de risco para paralisia cerebral (PC) em crianças de Bangladesh. MÉTODO: O Registro de PC de Bangladesh (RPCB) é uma base de dados populacional em andamento para vigilância de crianças com PC de uma área geograficamente definida de Bangladesh. Os casos foram definidos com base nos critérios do Vigilância da PC na Europa e do Registro Australiano de PC após avaliação clínica e identificação pelo método pelo informante principal RESULTADOS: No total, 726 crianças com PC foram identificadas entre Janeiro 2015 e Dezembro 2016. A média de idade foi 7 anos e 7 meses (desvio padrão [DP] 4a 6m; variação: 4,8m-18a; mediana 7a 1,2m; 61,8% do sexo masculino, 38,2% do sexo feminino). A média de idade no momento do diagnóstic de PC foi de 5 anos e 2 meses (DP 3,8). A prevalência observada foi 3,4 a cada 1000 crianças (intervalo de confiança [IC] a 95% 3,2-3,7), resultando em uma estimativa de 233.514 crianças (IC 95% 219.778-254.118) com PC em Bangladesh. A maioria (79,6%) tinha PC espástica. No total, 79,6% das crianças com PC tinha pelo menos uma deficiência associada (linguagem 67,6%, intelectual 39,0%, epilepsia 23,7%, visual 10,2%, e auditiva 10,2%). No total, 78,2% nunca recebeu reabilitação. INTERPRETAÇÃO: Em Bangladesh, o peso da PC é alto, e o diagnóstico é substancialmente tardio, limitando as oportunidades de intervenção precoce. Há carência de serviços disponíveis, e a maioria das crianças apresentou fatores de risco preveníveis.

Mortality in children with cerebral palsy in rural Bangladesh: a population-based surveillance study.

AIM: To determine the mortality rate, immediate cause of death (CoD), and predictors of death in children with cerebral palsy (CP) in rural Bangladesh. METHOD: We carried out a prospective population-based surveillance study of children with CP aged 0 to 18 years registered with the Bangladesh Cerebral Palsy Register (BCPR) between January 2015 and December 2016, with subsequent follow-up until December 2017. Verbal autopsy was applied to assign immediate CoD. Crude mortality rates, hazard ratios of death, and survival probabilities were estimated. RESULTS: Twenty-nine of the 678 children in the BCPR died during the study period, resulting in a crude mortality rate of 19.5 per 1000 person-years of observation (total follow-up duration 1486.8 person-years; mean 2y [standard deviation 6mo]). The leading immediate CoD was meningitis (n=9) and pneumonia (n=8). Survival probability and hazard ratio of death was significantly associated with age, Gross Motor Functional Classification System level, and associated impairments. Severe underweight and/or severe stunting was significantly overrepresented among deceased children than others in the cohort (p<0.05) when compared with the World Health Organization reference population. INTERPRETATION: The majority of deaths were due to potentially preventable causes. The life expectancy of these children could have been extended by ensuring primary healthcare and nutritional supplementation. WHAT THIS PAPER ADDS: Mortality rate in children with cerebral palsy (CP) in rural Bangladesh is 19.5 per 1000 person-years. The majority of children with CP died from potentially preventable and treatable conditions. Motor severity, associated impairments, and malnutrition make children with CP vulnerable to premature death in rural Bangladesh.

Cross-cultural validation of the Bengali version KIDSCREEN-27 quality of life questionnaire.

BACKGROUND: Measuring the health-related quality of life (HRQoL) of adolescents, including those with cerebral palsy (CP) (the major cause of childhood physical disability worldwide) in Bangladesh is pertinent although there is a dearth of validated instruments for assessing this concept. For application in a case-control study comparing HRQoL between adolescents with CP and peers without disability in Bangladesh (a typical low- and middle-income country) we cross-culturally translated and psychometrically tested KIDSCREEN-27. METHODS: KIDSCREEN-27 was translated to Bengali using forward and backwards translation protocol and interviewer administered to adolescents with CP and their age and sex matched peers without disability. Primary caregivers were included for proxy-report. Sociodeomgraphic characterists and clinical information were extracted from the Bangladesh Cerebral Palsy Register (BCPR) and adolescent mental health was assessed using the Bengali version Strenghts and Difficulties Questionnaire (SDQ). Feasibility, floor and ceiling effect, internal consistency, content and construct validity of KIDSCREEN-27 were tested. RESULTS: Feasibility, floor and ceiling effect and internal consistency of KIDSCREEN-27 was good for both self- and proxy-report questionnaires; nil missing scores except 'school environment' (11.0% to 74.7%) which correlated to rates of non-school attendance; floor and ceiling effect ≤10.4% except 'peers and social support' 23.4%; Cronbach's alpha 0.67 to 0.91. Instrument validity was strong; factor analysis reflected original instrument dimensions within one to three factors and difference in known groups was observed by CP and adolescent mental health (p < 0.05). CONCLUSION: KIDSCREEN-27 successfully translated to Bengali and both the self and proxy-report questionnaires showed good psychometric properties indicating suitability for case-control assessment of HRQoL between adolescents with CP and peers without disability in Bangladesh.

Hip dysplasia among children with spastic cerebral palsy in rural Bangladesh.

BACKGROUND: Hip dysplasia is common among children with cerebral palsy (CP), particularly in spastic CP. It can result in pain, reduced function and quality of life. However, the burden of hip dysplasia among children with CP in llow-and middle-income countries (LMICs) like Bangladesh is unknown. We aimed to define the burden of hip dysplasia among children with spastic CP in Bangladesh. METHODS: This study includes a subset of the Bangladesh CP Register (BCPR) study cohort who were registered between January and March 2015. The BCPR is a population-based surveillance of children with CP (aged < 18 years) operating in a northern sub-district (Shahjadpur; child population ~ 226,114) of Bangladesh. Community-based key informant's method (KIM) survey conducted to identify children with CP in the surveillance area. A diagnosis of CP was made based on clinical history and examination by the study physicians and physiotherapist. Study participants had an antero-posterior (AP) X-ray of their pelvis. The degree of subluxation was assessed by calculating the migration percentage (MP). RESULTS: During the study period, 196 children with CP were registered, 144 had spastic CP. 40 children with spastic CP (80 hips) had pelvic X-Rays (mean age 9.4 years, range 4.0-18.0 years) and 32.5% were female. Gross Motor Function Classification System (GMFCS) showed 37.5% (n = 15) with GMFCS level I-II and 62.5% (n = 25) with GMFCS level III-V. Twenty percent (n = 8) of the children had hip subluxation (MP: 33-80%). Osteopenic changes were found in 42.5% (n = 17) children. CONCLUSIONS: To the best of our knowledge this is one of the first studies exploring hip dysplasia among children with spastic CP in Bangladesh. Our findings reflect that hip dysplasia is common among children with spastic CP. Introduction of hip surveillance programmes is imperative for prevention of secondary complications, reduced function and poor quality of life among these children.

Use of a Developmental Milestone Chart (DMC) in Rural Bangladesh to Educate Health Workers and Stimulate Referral for Early Diagnosis and Intervention.

We aimed to determine the feasibility of using a simplified Developmental Milestone Chart (DMC) for assessment of neurodevelopmental status of children of age ≥1 month and ≤8 years. Participants were assessed by medical practitioners using DMC as part of regular health checkups in three sub-districts in Bangladesh between January and May 2017. Total 256 children were recruited (41.0% girls, mean age 1.3 ± 1.6 years). Total 107 children (41.8%) failed at least one and 3 (1.2%) failed all four developmental milestones. Majority missed motor milestones (75.6%, n = 81). Four medical practitioners trained on the use of DMC deemed it to be an appropriate tool for developmental screening as part of regular health checkups/care in terms of acceptability, practicality and implementation. In countries with limited facilities, a simplified instrument such as the DMC can be administered by medical practitioners in rural settings. However, further studies are required to establish the validity of DMC before it could be adopted into routine clinical practices.

Interventions to prevent respiratory diseases - Nutrition and the developing world.

Malnutrition is a major cause of morbidity and mortality in developing countries and nutrition plays a critical role in both acute and chronic respiratory conditions. Inadequacies in the nutritional requirements of a developing lung in utero and in early life can compromise the respiratory system integrity and result in poor lung function, reduced protection against infections, greater likelihood of acute illnesses in childhood and chronic illness in adulthood. Nutritional interventions harness great potential in reducing respiratory illness related morbidity and mortality in the developing world. In this review we have summarized the findings from published systematic reviews/meta-analysis, experimental and observational studies that looked into different nutritional interventions for preventing respiratory diseases in developing countries.

Clinically Relevant Genes Identified in Cerebral Palsy Cohorts Following Evaluation of the Clinical Description and Phenotype: A Systematic Review.

A growing number of genes have been identified in individuals with cerebral palsy (CP); however, many of these studies have poor compliance with the cerebral palsy clinical description. This systematic review aimed to assess the quality of the cerebral palsy clinical description/phenotype in cerebral palsy genetic studies published between 2010 and 2024 and report clinically relevant genes based on the quality of the cerebral palsy phenotype. An expert panel developed 6 criteria to review the reported cerebral palsy phenotype/description for each included study. Clinically relevant genes were extracted from each study and stratified into 2 tiers based on the quality. Eighteen studies were included. There was high confidence in the reported cerebral palsy description/phenotype from 8 studies. Of the initial 373 clinically relevant genes, 85 were tier II genes. Individual cerebral palsy motor disorder and phenotype data were absent for 349 of these individuals, limiting further analysis. The tier I gene list was composed of 6 genes: ATL1, COL4A1, GNAO1, KIF1A, SPAST, and TUBA1A. Bilateral spasticity was the most common motor disorder reported in individuals with variants in all 6 genes, and most individuals had accompanying conditions. Prioritizing the accurate reporting of motor and nonmotor phenotypes is crucial for future cerebral palsy genetic studies to further understand the underlying neurobiology.

Improving epilepsy control among children with cerebral palsy in rural Bangladesh: a prospective cohort-based study.

OBJECTIVE: To define the prevalence and seizure subtypes among children with cerebral palsy (CP) in rural Bangladesh and explore barriers to optimum epilepsy control. DESIGN: Prospective cohort study. SETTING: The study was conducted in Shahjadpur, a rural subdistrict of Bangladesh. PARTICIPANTS: Children (<18 years) with CP and epilepsy identified using the Bangladesh CP Register (BCPR) in the study site. METHODS: Assessments were conducted in three focused epilepsy clinics overseen by a paediatric neurologist between December 2016 and January 2018, with intervening phone and video-conference follow-ups. Details of event type, frequency and medication compliance were collected. Antiepileptic drugs (AEDs) were prescribed based on seizure type, family income, comorbidity and medication availability. RESULTS: 23.4% (170/726) of the BCPR cohort had a clinical diagnosis of epilepsy of whom 166 were assessed. Following the focused epilepsy clinics, 62.0% (103/166) children were clinically determined to have ongoing epileptic seizures. 62.1% (64/103) had generalised onset tonic clonic seizures, 27.2% (28/103) had focal onset seizures with impaired awareness and 10.7% (11/103) had other seizure types. None of the children with prolonged seizures (31/103) had an emergency seizure management plan. Non-epileptic events were being pharmacologically treated as seizures in 18.1% (30/166) children. Financial constraints were the main reason for non-compliance on follow-up. CONCLUSIONS: Gaps in optimum epilepsy management in rural Bangladesh are amenable to improvement anchored with local healthcare workers. Training and clinical care focused on recognition of common seizure types, seizure mimics and rationalising use of available AEDs can be facilitated by better referral pathways and telehealth support.

Data on cerebral palsy in Vietnam will inform clinical practice and policy in low and middle-income countries.

PURPOSE: To document known risk factors, clinical severity, associated impairments and rehabilitation status of children presenting with cerebral palsy (CP) to the National Children's Hospital (NCH) in Hanoi, Vietnam. MATERIALS AND METHODS: Active prospective ascertainment of cases of CP presenting between June and November 2017 to the NCH using surveillance modelled on the Paediatric Active Enhanced Disease Surveillance system in Australia. RESULTS: Data were collected on 765 children with CP (mean age: 2 years 7 months (SD 2 y 6 mo). Mean age at diagnosis was 1 year 8 months (SD 1 y 9 mo). Children predominantly had spastic CP (95.2%, n = 729), most were quadriplegic (69.6%, n = 532) and 60.3% (n = 454) were Gross Motor Functional Classification System level III-V. Of the children 76.2% (n = 583) had one/more associated impairments. 36.3% (n = 276) had presumed perinatal asphyxia, 26.5% (n = 202) were preterm. Physiotherapy (94.3%, n = 663) was the most common form of intervention used. Only 2.6% (n = 12) of the children who would have benefitted from assistive devices had wheelchairs. CONCLUSION: We established hospital-based surveillance of CP in Hanoi and confirmed a high burden and severity of CP with potentially preventable risk factors. These data will inform clinician training and health policy and identify need for evidence-based care and assistive devices.IMPLICATIONS FOR REHABILITATIONWe identified a high number of children with severe forms of cerebral palsy (CP) in Hanoi, Vietnam through hospital-based surveillance.There is an urgent need for clinician training and access to and use of evidence-based interventions including assistive technology.This study will inform local capacity building and health policy for improved diagnosis and care of children with CP in Vietnam and other low and middle-income countries.

Nutrition Interventions for Children with Cerebral Palsy in Low- and Middle-Income Countries: A Scoping Review.

BACKGROUND: Malnutrition is substantially higher among children with cerebral palsy (CP) in low- and middle-income countries (LMICs) when compared with the general population. Access to appropriate interventions is crucial for better management of malnutrition and nutritional outcomes of those children. We aimed to review the existing evidence on nutrition interventions for children with CP in LMICs. METHODS: Online databases, i.e., PubMed and Scopus, and Google Scholar were searched up to 10 January 2022, to identify peer-reviewed publications/evidence on LMIC focused nutritional management guidelines/interventions. Following title screening and abstract review, full articles that met the inclusion/exclusion criteria were retained for data charting. Information about the study characteristics, nutrition interventions, and their effectiveness were extracted. Descriptive data were reported. RESULTS: Eight articles published between 2008 and 2019 were included with data from a total of n = 252 children with CP (age range: 1 y 0 m-18 y 7 m, 42% female). Five studies followed experimental design; n = 6 were conducted in hospital/clinic/center-based settings. Four studies focused on parental/caregiver training; n = 2 studies had surgical interventions (i.e., gastrostomy) and n = 1 provided neurodevelopmental therapy feeding intervention. Dietary modification as an intervention (or component) was reported in n = 5 studies and had better effect on the nutritional outcomes of children with CP compared to interventions focused on feeding skills or other behavioral modifications. Surgical interventions improved nutritional outcomes in both studies; however, none documented any adverse consequences of the surgical interventions. CONCLUSION: There is a substantial knowledge gap on nutrition interventions for children with CP in LMICs. This hinders the development of best practice guidelines for the nutritional management of children with CP in those settings. Findings suggest interventions directly related to growth/feeding of children had a better outcome than behavioral interventions. This should be considered in planning of nutrition-focused intervention or comprehensive services for children with CP in LMICs.

The epidemiology, clinical, biochemical, immunological and radiological features of youth onset type 2 diabetes mellitus in the state of Qatar.

Objectives: To describe the epidemiology, clinical, biochemical, immunological and radiological aspects of youth with type 2 diabetes. Methods: Patients under 18 year of age with type 2 diabetes were recruited from 2018 to 2020, clinical data collected, autoantibodies (GAD65, IAA, IA2 and ZnT8), insulin, ALT and c-peptide were measured. Hepatic ultrasound was performed for assessment of non-alcoholic fatty liver disease (NAFLD). Results: 104 patients were identified. The incidence in 2020 and prevalence per 100,000 was 2.51 and 23.7, respectively. The age of onset was between 8.5 and 18 years with 74% of the patients being of Qatari nationality. Males were more affected than females (1.5/1). Overweight/obesity was present in 98% of all the patients, a positive family history (either both parents or a single parent) in 71% and maternal gestational diabetes mellitus (GDM) in 60% of patients. More than 90% of the patients had acanthosis nigricans. 5 patients had 1 autoantibody positivity and hepatic ultrasound detected evidence of NAFLD in majority of patients. Conclusion: Obesity, maternal GDM and family history of diabetes were the key risk factors for the development of type 2 diabetes. Autoantibody positivity may be present in youth type 2 diabetes. As youth type 2 diabetes is associated with early onset microvascular and macrovascular complications, these findings have important social and health budget implications for Qatar. Tackling the burden of maternal GDM and childhood obesity and building programmes for early detection and intervention, are therefore, essential to reduce the risk of future complications.