Outcome of treatment of proximal tibial plateau fractures by minimally invasive percutaneous plating osteosynthesis technique

Background: Fractures of the proximal tibia are accompanied by a wide range of severity which may include stable undisplaced fractures with minimal soft tissue injury to highly comminuted unstable fractures, and severe soft tissue involvement. With the better understanding of fracture healing biology and biomechanics of fracture fixation and healing, the trend of treatment is towards biological fixation, which can be accomplished by Minimally Invasive Percutaneous Plating Osteosynthesis (MIPPO) technique.Methods: Demographic data of patients were recorded on admission and thorough history and clinical examination was done. The fractures were assessed for soft tissue injuries and followed by radiological assessment of fracture with schatzkers classification. The surgeries included anterolateral and anteromedial approaches for all patients with ‘inverted hockey stick incision’ and were treated with MIPPO. They were regularly followed up at 6-8 weeks interval till complete fracture union. A clinical and radiological evaluation was carried out using the modified Rasmussen clinical and radiological criteria.Results: Out of the 20 patients treated, most of them were males and belonged to the age group of 20-40 years (75%).  Unilateral fractures were more common than bilateral fractures and were of the type 4 and type 5 of Schatzkers classification which was usually associated with high velocity RTA. One patient each had infection, varus deformity and knee joint stiffness. 10 fractures gave excellent result, 7 fractures healed with good results. Only 2 of the patients showed fair results and 1 had poor result.  Conclusions: All the fractures treated with MIPPO technique was found to be rapidly healing by secondary fracture union and hence achieving strong bone union across the fracture site due to inherent benefits of less tissue damage and minimal disturbance of fracture site biology

Global and regional prevalence of disabilities among children and adolescents : analysis of findings from global health databases

Objective: The United Nations' Sustainable Development Goals (SDGs) require population-based data on children with disabilities to inform global policies and intervention programs. We set out to compare the prevalence estimates of disabilities among children and adolescents younger than 20 years as reported by the world's leading organizations for global health statistics. Methods: We purposively searched the disability reports and databases of the United Nations Children's Fund (UNICEF), the World Health Organization (WHO), the World Bank and the Global Burden of Diseases (GBD) Study. We analyzed the latest disability data reported by these organizations since 2015. We examined the methodologies adopted in generating the reported prevalence estimates and evaluated the degree of agreement among the data sources using Welch's test of statistical difference, and the two one-sided t-test (TOST) for statistical equivalence. Results: Only UNICEF and GBD provided the most comprehensive prevalence estimates of disabilities in children and adolescents. Globally, UNICEF estimated that 28.9 million (4.3%) children aged 0–4 years, 207.4 million (12.5%) children aged 5–17 years and 236.4 million (10.1%) children aged 0–17 years have moderate-to-severe disabilities based on household surveys of child functional status. Using the UNICEF estimated prevalence of 10.1%, approximately 266 million children aged 0–19 years are expected to have moderate-to-severe disabilities. In contrast, GBD 2019 estimated that 49.8 million (7.5%) children aged under 5 years, 241.5 million (12.6%) children aged 5–19 years and 291.3 million (11.3%) children younger than 20 years have mild-to-severe disabilities. In both databases, Sub-Saharan Africa and South Asia accounted for more than half of children with disabilities. A comparison of the UNICEF and GBD estimates showed that the overall mean prevalence estimates for children under 5 years were statistically different and not statistically equivalent based on ±3 percentage-point margin. However, the prevalence estimates for children 5–19 years and < 20 years were not statistically different and were statistically equivalent. Conclusion: Prevalence estimates of disabilities among children and adolescents generated using either functional approach or statistical modeling appear to be comparable and complementary. Improved alignment of the age-groups, thresholds of disability and the estimation process across databases, particularly among children under 5 years should be considered. Children and adolescents with disabilities will be well-served by a variety of complementary data sources to optimize their health and well-being as envisioned in the SDGs

The Fallacy of Using Administrative Data in Assessing the Effectiveness of Food Fortification. Comment on: "Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset. Nutrients 2020, 12, 247".

Our objective in this comment is to highlight several limitations in an ecological research study that was published in Nutrients by Murphy and Westmark (2020) in January 2020. The study used data from the Food Fortification Initiative (FFI) website, and applying an ecological study design, made an error of "ecologic fallacy" in concluding that "national fortification with folic acid is not associated with a significant decrease in the prevalence of neural tube defects (NTDs) at the population level". We list study limitations that led to their erroneous conclusions, stemming from incorrect considerations regarding NTD prevalence, the average grain availability for a country, the fortification coverage in a country, the population reach of fortified foods within a country, and the absence of the consideration of fortification type (voluntary vs. mandatory), country-specific policies on elective terminations for NTD-affected pregnancies, stillbirth proportions among those with NTDs, and fortification implementation. FFI data are derived from many sources and intended for fortification advocacy, not for hypothesis testing. The flawed study by Murphy & Westmark (2020) in Nutrients promotes a confusing and incorrect message to stakeholders, misguides policy makers, and hinders progress in global NTD prevention through a cost-effective, safe, and effective intervention: the mandatory large-scale folic acid fortification of staple foods

Estimates of global and regional prevalence of neural tube defects for 2015: a systematic analysis.

Neural tube defects (NTDs) are associated with substantial mortality, morbidity, disability, and psychological and economic costs. Many are preventable with folic acid, and access to appropriate services for those affected can improve survival and quality of life. We used a compartmental model to estimate global and regional birth prevalence of NTDs (live births, stillbirths, and elective terminations of pregnancy) and subsequent under-5 mortality. Data were identified through web-based reviews of birth defect registry databases and systematic literature reviews. Meta-analyses were undertaken where appropriate. For 2015, our model estimated 260,100 (uncertainty interval (UI): 213,800-322,000) NTD-affected birth outcomes worldwide (prevalence 18.6 (15.3-23.0)/10,000 live births). Approximately 50% of cases were elective terminations of pregnancy for fetal anomalies (UI: 59,300 (47,900-74,500)) or stillbirths (57,800 (UI: 35,000-88,600)). Of NTD-affected live births, 117,900 (∼75%) (UI: 105,500-186,600) resulted in under-5 deaths. Our systematic review showed a paucity of high-quality data in the regions of the world with the highest burden. Despite knowledge about prevention, NTDs remain highly prevalent worldwide. Lack of surveillance and incomplete ascertainment of affected pregnancies make NTDs invisible to policy makers. Improved surveillance of all adverse outcomes is needed to improve the robustness of total NTD prevalence estimation, evaluate effectiveness of prevention through folic acid fortification, and improve outcomes through care and rehabilitation

Descriptive and risk factor analysis for choanal atresia: The National Birth Defects Prevention Study, 1997–2007

Choanal atresia causes serious posterior nasal obstruction. This defect is the leading cause of nasal surgery in newborns, although its etiology is largely unknown. Data from the National Birth Defects Prevention Study, a population-based case–control study, were used to examine associations between maternal self-reports of exposures and occurrence of choanal atresia in their offspring. Overall, 117 case and 8350 control mothers with deliveries from 1997 through 2007 provided telephone interview reports of pre-pregnancy (one year before conception) and periconceptional (one month before through three months after conception) exposures. The exposures analyzed were pre-pregnancy dietary intake, pre-pregnancy and periconceptional caffeine consumption, and periconceptional cigarette smoking, alcohol drinking, and medication use. Independent associations between each exposure and all choanal atresia cases combined (n = 117) and isolated choanal atresia cases (those without additional unrelated major defects; n = 61) were examined. Odds ratios (ORs), both unadjusted (uORs) and adjusted (aORs) for potential confounders, and 95% confidence intervals (CIs) were estimated using unconditional logistic regression analysis. For all choanal atresia cases combined, positive associations were observed with maternal pre-pregnancy intake in the highest quartile for vitamin B-12 (aOR = 1.9; CI = 1.1,3.1), zinc (aOR = 1.7; CI = 1.0,3.1), and niacin (aOR = 1.8; CI = 1.0,3.1), and intake in the lowest quartile for methionine (aOR = 1.6; CI = 1.0,2.6) and vitamin D (aOR = 1.6; CI = 1.0,2.4) compared to intake in the two intermediate quartiles combined. Further, a positive association was observed with periconceptional use of thyroid medications (uOR = 2.6; CI = 1.0,6.3) compared to no use of such medications. Among isolated choanal atresia cases, negative associations were observed for pantothenic acid (aOR = 0.4; CI = 0.2,0.9) and fat (aOR = 0.5; 95% CI = 0.2,1.0) intake in the lowest quartile compared to that in the intermediate quartiles, and positive associations were observed for periconceptional cigarette smoking (aOR = 2.3; CI = 1.1,4.7) compared to no smoking and pre-pregnancy daily coffee intake of 3 or more cups (aOR = 2.5; CI = 1.1,5.6) compared to intake of less than 1 cup per day. The positive association for periconceptional exposure to thyroid medications also persisted for isolated choanal atresia cases (uOR = 4.0; CI = 1.1,11.2). Because of the large number of associations tested, these findings may be due to chance. Alternatively, they may contribute new hypotheses regarding the etiology of choanal atresia; thus, requiring replication in additional studies

GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers.

Synthetic lethal interactions, where the simultaneous but not individual inactivation of two genes is lethal to the cell, have been successfully exploited to treat cancer. GATA3 is frequently mutated in estrogen receptor (ER)-positive breast cancers and its deficiency defines a subset of patients with poor response to hormonal therapy and poor prognosis. However, GATA3 is not yet targetable. Here we show that GATA3 and MDM2 are synthetically lethal in ER-positive breast cancer. Depletion and pharmacological inhibition of MDM2 significantly impaired tumor growth in GATA3-deficient models in vitro, in vivo and in patient-derived organoids/xenograft (PDOs/PDX) harboring GATA3 somatic mutations. The synthetic lethality requires p53 and acts via the PI3K/Akt/mTOR pathway. Our results present MDM2 as a therapeutic target in the substantial cohort of ER-positive, GATA3-mutant breast cancer patients. With MDM2 inhibitors widely available, our findings can be rapidly translated into clinical trials to evaluate in-patient efficacy

Cerebral palsy and developmental intellectual disability in children younger than 5 years: Findings from the GBD-WHO Rehabilitation Database 2019.

Objective: Children with developmental disabilities are associated with a high risk of poor school enrollment and educational attainment without timely and appropriate support. Epidemiological data on cerebral palsy and associated comorbidities required for policy intervention in global health are lacking. This paper set out to report the best available evidence on the global and regional prevalence of cerebral palsy (CP) and developmental intellectual disability and the associated "years lived with disability" (YLDs) among children under 5 years of age in 2019. Methods: We analyzed the collaborative 2019 Rehabilitation Database of the Global Burden of Disease (GBD) Study and World Health Organization for neurological and mental disorders available for 204 countries and territories. Point prevalence and YLDs with 95% uncertainty intervals (UI) are presented. Results: Globally, 8.1 million (7.1-9.2) or 1.2% of children under 5 years are estimated to have CP with 16.1 million (11.5-21.0) or 2.4% having intellectual disability. Over 98% resided in low-income and middle-income countries (LMICs). CP and intellectual disability accounted for 6.5% and 4.5% of the aggregate YLDs from all causes of adverse health outcomes respectively. African Region recorded the highest prevalence of CP (1.6%) while South-East Asia Region had the highest prevalence of intellectual disability. The top 10 countries accounted for 57.2% of the global prevalence of CP and 62.0% of the global prevalence of intellectual disability. Conclusion: Based on this Database, CP and intellectual disability are highly prevalent and associated with substantial YLDs among children under 5 years worldwide. Universal early detection and support services are warranted, particularly in LMICs to optimize school readiness for these children toward inclusive education as envisioned by the United Nations' Sustainable Development Goals

Neural tube defects as a cause of death among stillbirths, infants, and children younger than 5 years in sub-Saharan Africa and southeast Asia: an analysis of the CHAMPS network

BACKGROUND: Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia. METHODS: This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site. FINDINGS: Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84-23·02]), among female individuals (4·40 [2·44-7·93]), and among those whose mothers had no antenatal care (2·48 [1·12-5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7-8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9-116·4]), 4-23 times greater than in any other site. INTERPRETATION: CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects. FUNDING: Bill & Melinda Gates Foundation