Analysis of the Correlation between FH and PCSK9 and APOB Gene Mutations in Han and Mongolian Populations of the Hulunbuir.

BACKGROUND: The goal of the study was to provide an individual and precise genetic and molecular biological basis for the early prevention, diagnosis, and treatment of local FH by analyzing the risk factors for the development of FH in Han and Mongolian patients in the Hulunbuir, comparing the lipid levels of FH patients of the two ethnicities, and assessing differences in mutations to two genes between the two ethnic groups. METHODS: Twenty cases each of Han Chinese and Mongolian healthy controls and fifty patients who each met the inclusion criteria from November 2021 to December 2022 in five general hospitals in Hulunbuir were selected. Multifactor logistic analysis was used to analyze the risk factors associated with the development of FH. We used t-tests to analyze statistical differences in lipid levels between the groups, and Sanger sequencing to detect the dis-tribution of common mutation sites of PCSK9 and APOB in all study subjects. The mutation rates and differences between regions and ethnic groups were summarized and compared. RESULTS: 1) Gender, age, alcohol consumption, dietary status, and a family history of FH were risk factors associated with the development of FH. 2) TC, LDL-C, and APOB were significantly higher in Mongolian cases than Han cases (p < 0.05). sdLDL-C was not statistically different between the two ethnicities (p > 0.05). 3) We detected four (8%) heterozygous mutations at the PCSK9 gene E670G mutation site in the Han case group and a total of nine (18%) mutations at this site in the Mongolian cases, including one (2%) homozygous and eight (16%) heterozygous mutations. One case of a heterozygous mutation was detected in the Mongolian control group. We detected a total of ten (20%) mutations at the APOB gene rs1367117 mutation site in the Han case group, including eight (16%) heterozygous and two (4%) homozygous mutations, 11 cases (22%) of heterozygous mutations in the Mongolian case group, two cases of heterozygous mutations in the Han control group, and one case of a heterozygous mutation in the Mongolian control group. 4) The D374Y and S127R mutation sites of PCSK9 and the R3500Q mutation site of APOB were not detected in any of the study subjects. CONCLUSIONS: The mutation sites of the PCSK9 and APOB genes in FH patients in Hulunbuir are different from other regions, and the mutation rate is higher than in other regions. Therefore, we recommend that the mutation sites of the PCSK9 and APOB genes described herein be used as clinical detection indicators to assist the diagnosis of FH in this region.

Respiratory Syncytial Virus and Influenza Infections in Children in Ulaanbaatar, Mongolia, 2015-2021.

BACKGROUND: Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. METHODS: This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. RESULTS: Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. CONCLUSION: In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.

Nose of dog, eye of elk, and wolf's liver: exploring the interconnectedness of Indigenous health and foraging among the Dukha reindeer herders of Mongolia.

Recent studies show that Traditional Ecological Knowledge (TEK) of Indigenous Peoples' food systems and the transfer of that knowledge to their children are critical to physical and mental health, promote the transfer of language and culture, and further resilience. The aim of this exploratory, medical ecological study was to document TEK about foraging and plant use among the Dukha, a small, semi-nomadic reindeer herding community in Northern Mongolia. Field research was conducted at multiple remote camps in 2019 and 2023. Methods included semi-structured, open-ended interviews (N = 16), photo identification, and participant observation (N = 34 families). Study Informants identified 27 foraged plants. Results placed Dukha foraging practices within a framework illustrating the interconnectedness of their worldview and cultural norms, including the physical and spiritual aspects of the landscape, with health, illness, and curing. Dukha curative knowledge of the flora aligns with both Traditional Mongolian Medicine (TMM) and scientific studies on healing and preventative care. Through foraging and plant use, the Dukha balance relationships with the land and spirits, benefit from better nutrition and physical activity, utilise healing qualities of indigenous flora, and foster the intergenerational transfer of language and traditional knowledge.

Delays in health seeking, diagnosis and treatment for tuberculosis patients in Mongolia: an analysis of surveillance data, 2018-2021.

Early diagnosis and treatment of infectious tuberculosis (TB) is essential to the attainment of global targets specified in the End TB Strategy. Using case-based TB surveillance data, we analysed delays in health seeking, diagnosis and treatment among TB patients in Mongolia from 2018 to 2021. We calculated the median and interquartile range (IQR) for "diagnostic delay," defined as the time from symptom onset to diagnosis, subdivided into "health-seeking delay" (time from symptom onset to first visit to a health facility) and "health facility diagnostic delay" (time from first health facility visit to diagnosis), and for "treatment delay," defined as the time from diagnosis to start of treatment. We also calculated "total delay," defined as the time from symptom onset to treatment start. Based on data for 13 968 registered TB patients, the median total delay was estimated to be 37 days (IQR, 19-76). This was mostly due to health-seeking delay (median, 23 days; IQR, 8-53); in contrast, health facility diagnostic delay and treatment delay were relatively short (median, 1 day; IQR, 0-7; median, 1 day; IQR, 0-7, respectively). In 2021, health-seeking delay did not differ significantly between men and women but was shorter in children than in adults and shorter in clinically diagnosed than in bacteriologically confirmed TB cases. Health-seeking delay was longest in the East region (median, 44.5 days; IQR, 20-87) and shortest in Ulaanbaatar (median, 9; IQR, 14-64). TB treatment delay was similar across sexes, age groups and types of TB diagnosis but slightly longer among retreated cases and people living in Ulaanbaatar. Efforts to reduce TB transmission in Mongolia should prioritize decreasing delays in health seeking.

Estimating Asymptomatic and Symptomatic Transmission of the COVID-19 First Few Cases in Selenge Province, Mongolia.

BACKGROUND: Following the first locally transmitted case in Sukhbaatar soum, Selenge Province, we aimed to investigate the ultimate scale of the epidemic in the scenario of uninterrupted transmission. METHODS: This was a prospective case study following the locally modified WHO FFX cases generic protocol. A rapid response team collected data from November 14 to 29, 2020. We created a stochastic process to draw many transmission chains from this greater distribution to better understand and make inferences regarding the outbreak under investigation. RESULTS: The majority of the cases involved household transmissions (35, 52.2%), work transmissions (20, 29.9%), index (5, 7.5%), same apartment transmissions (2, 3.0%), school transmissions (2, 3.0%), and random contacts between individuals transmissions (1, 1.5%). The posterior means of the basic reproduction number of both the asymptomatic cases R 0 Asy $$ {R}_0^{Asy} $$ and the presymptomatic cases R 0 Pre $$ {R}_0^{Pre} $$ (1.35 [95% CrI 0.88-1.86] and 1.29 [95% CrI 0.67-2.10], respectively) were lower than that of the symptomatic cases (2.00 [95% Crl 1.38-2.76]). CONCLUSION: Our study highlights the heterogeneity of COVID-19 transmission across different symptom statuses and underscores the importance of early identification and isolation of symptomatic cases in disease control. Our approach, which combines detailed contact tracing data with advanced statistical methods, can be applied to other infectious diseases, facilitating a more nuanced understanding of disease transmission dynamics.

Improvement of the anthropogenic emission rate estimate in Ulaanbaatar, Mongolia, for 2020-21 winter.

Ulaanbaatar (UB), the fast-growing capital of Mongolia, is known for its world's worst level of particulate matter (PM) concentrations in winter. However, current anthropogenic emission inventories over the UB are based on data from more than fifteen years ago, and satellite observations are scarce because UB is in high latitudes. During the winter of 2020-21, the first period of the Fine Particle Research Initiative in East Asia considering the National Differences (FRIEND), several times higher concentrations of PM in UB compared to other urban sites in East Asia were observed but not reproduced with a chemical transport model mainly due to the underestimated anthropogenic emissions. Therefore, we devised a method for sequentially adjusting emissions based on the reactivity of PM precursors using ground observations. We scaled emission rates for the inert species (CO, elemental carbon (EC), and organic carbon (OC)) to reproduce their observed ambient concentrations, followed by SO2 to reproduce the concentration of SO42-, which was examined to have the least uncertainty based on the abundance of observed NH3, and finally NO and NH3 for NO3-, and NH4+. This improved estimation is compared to regional inventories for Asia and suggests more than an order of magnitude increase in anthropogenic emissions in UB. Using the improved emission inventory, we were able to successfully reproduce independent observation data on PM2.5 concentrations in UB in December 2021 from the U.S. Embassy. During the campaign period, we found more than 50% of the SO42-, NO3-, and NH4+ increased in UB due to the improvement could travel to Beijing, China (BJ), and about 20% of the SO42- could travel to Noto, Japan (NT), more than 3000 km away. Also, the anthropogenic emissions in UB can effectively increase OC, NO3-, and NH4+ concentrations in BJ when Gobi dust storms occur.

Factors associated with recurrence in patients with oral cancer in Mongolia.

INTRODUCTION: In Mongolia, there has been limited research on the posttreatment survival rate, recurrence, and occurrence of oral cancer. The goal of this study is to investigate the risk factors that contribute to the recurrence of oral cancer to increase survival rates, facilitate early detection, and improve treatment accuracy. METHOD: A retrospective cohort method was used, with medical records from 173 patients diagnosed with squamous cell carcinoma of the mouth at the National Cancer Center of Mongolia's Department of Head and Neck Surgery, Radio, and Chemotherapy between 2012 and 2017. The Mongolian National University of Medical Sciences' Research Ethics Committee approved the project. RESULTS: The findings revealed that 109 cases (63.0%) were men and 64 (37.0%) were females, with a large proportion of patients (28.3%) falling between the ages of 61 and 70. Men had a 3.8 times higher risk of cancer recurrence than women (OR = 3.79, CI = 1.24-11.57). Furthermore, lymph node metastases and treatment were linked to oral cancer recurrence. CONCLUSION: This study offers light on the factors that influence the recurrence of oral cancer, giving useful insights for improving patient outcomes through early detection and proper treatment.

Risk factors associated with hepatitis D virus infection and preventive strategies in Mongolia.

BACKGROUND: Hepatitis D virus (HDV) infection is highly prevalent in Mongolia. We aimed to identify the risk factors associated with HDV infection, propose preventive strategies, and evaluate the outcomes of a 3-year collaborative project between Taiwan and Mongolia. METHODS: In 2016 and 2018, we conducted onsite visits to Mongolia. Mongolian investigators collected questionnaires focusing on risk factors, demographic characteristics, and serum samples for acute HDV infections. Furthermore, 19 Mongolian seed teachers participated in a 1-week workshop on infection control in Taiwan. Subsequently, these seed teachers trained more than 400 medical personnel in Mongolia. To assess secular changes in acute HDV infection, we reviewed the registration data from the National Center for Communicable Disease (NCCD) in Mongolia between 2011 and 2021. RESULTS: Among the 194 Mongolian patients, 108 had dual infection with hepatitis B virus (HBV) and HDV, while 86 had acute hepatitis B (AHB). Patients with HBV/HDV dual infections were older (28.6 vs 25.5 years, p = 0.030) and had lower rates of positive hepatitis B e antigen in their sera, lower rates of serum HBV DNA exceeding 2000 IU/mL, and higher rates of having received dental treatment (59.4% vs 40.5%, p = 0.014) and injection therapy (64.2% vs 44.0%, p = 0.009) compared with those with AHB. Analysis of NCCD data revealed that new HDV infection cases were more prevalent between 2011 and 2015 (111.20 ± 29.79 cases/y) and decreased to 54.67 ± 27.34 cases/y between 2016 and 2021 ( p = 0.010). CONCLUSION: Dental treatment and injections were associated with a higher risk of acute HDV infections in Mongolia. Through collaborative efforts, the incidence rate of HDV infection has declined in recent years.

Questionnaire survey on public awareness of cleft lip with/without palate in Mongolia.

The frequency of cleft lip with/without palate (CL/P) in the Mongolian population is approximately 1 in 1314 live births. This research aims to disseminate information about this congenital disability to the public to better understand CL/P, and people's fissures, and review administrative measures, as there is a lack of research in this area. A questionnaire survey was conducted using Google Forms, with 1000 Mongolian participants. Most participants (86.7%) said they had knowledge of the word, whereas 86.2% said they had knowledge of the condition. Most participants' answers were question-related disadvantages of CL/P patients, including statements such as "It's uncomfortable in human relationships" and "It makes an uncomfortable impression on the person you meet the first time." The results of this study revealed that most Mongolians were aware of CL/P and are concerned about patients. However, the causes of CL/P in the general population remain unknown, and further research is needed in this area.

Amycolatopsis mongoliensis sp. nov., a novel actinobacterium with antifungal activity isolated from a coal mining site in Mongolia.

A novel filamentous actinobacterium designated strain 4-36T showing broad-spectrum antifungal activity was isolated from a coal mining site in Mongolia, and its taxonomic position was determined using polyphasic approach. Optimum growth occurred at 30 °C, pH 7.5 and in the absence of NaCl. Aerial and substrate mycelia were abundantly formed on agar media. The colour of aerial mycelium was white and diffusible pigments were not formed. Phylogenetic analyses based on 16S rRNA gene sequence showed that strain 4-36T formed a distinct clade within the genus Amycolatopsis. The 16S rRNA gene sequence similarity showed that the strain was mostly related to Amycolatopsis lexingtonensis DSM 44544T and Amycolatopsis rifamycinica DSM 46095T with 99.3 % sequence similarity. However, the highest digital DNA-DNA hybridization value to closest species was 44.1 %, and the highest average nucleotide identity value was 90.2 %, both of which were well below the species delineation thresholds. Chemotaxonomic properties were typical of the genus Amycolatopsis, as the major fatty acids were C15 : 0, iso-C16 : 0 and C16 : 0, the cell-wall diamino acid was meso-diaminopimelic acid, the quinone was MK-9(H4), and the main polar lipids were diphosphatidylglycerol, phosphatidylmethanolamine and phosphatidylethanolamine. The in silico prediction of chemotaxonomic markers was also carried out by phylogenetic analysis. The genome mining for biosynthetic gene clusters of secondary metabolites in strain 4-36T revealed the presence of 34 gene clusters involved in the production of polyketide synthase, nonribosomal peptide synthetase, ribosomally synthesized and post-translationally modified peptide, lanthipeptide, terpenes, siderophore and many other unknown clusters. Strain 4-36T showed broad antifungal activity against several filamentous fungi. The phenotypic, biochemical and chemotaxonomic properties indicated that the strain could be clearly distinguished from other species of Amycolatopsis, and thus the name Amycolatopsis mongoliensis sp. nov. is proposed accordingly (type strain, 4-36T=KCTC 39526T=JCM 30565T).

Strengthening national salt reduction strategies using multiple methods process evaluations: case studies from Malaysia and Mongolia.

OBJECTIVE: To understand the extent to which national salt reduction strategies in Malaysia and Mongolia were implemented and achieving their intended outcomes. DESIGN: Multiple methods process evaluations conducted at the mid-point of strategy implementation, guided by theoretical frameworks. SETTING: Malaysia (2018-2019) and Mongolia (2020-2021). PARTICIPANTS: Desk-based reviews of related documents, interviews with key stakeholders (n 12 Malaysia, n 10 Mongolia), focus group discussions with health professionals in Malaysia (n 43) and health provider surveys in Mongolia (n 12). RESULTS: Both countries generated high-quality local evidence about salt intake and levels in foods and culturally specific education resources. In Malaysia, education and reformulation activities were delivered with moderate dose (quantity) but reach among the population was low. Within 5 years, Mongolia implemented education among schools, health professionals and food producers on salt reduction with high reach, but with moderate dose (quantity) and reach among the general population. Both countries faced challenges in implementing legislative interventions (mandatory salt labelling and salt limits in packaged foods) and both could improve the scaling up of their reformulation and education activities. CONCLUSIONS: In the first half of Malaysia's and Mongolia's strategies, both countries generated necessary evidence and education materials, mobilised health professionals to deliver salt reduction education and achieved small-scale reformulation in foods. Both subsequently should focus on implementing regulatory policies and achieving population-wide reach and impact. Process evaluations of existing salt reduction strategies can help strengthen intervention delivery, aiding achievement of WHO's 30 % reduction in salt intake by 2025 target.

Effect of Pneumococcal Conjugate Vaccine on Pneumonia Incidence Rates among Children 2-59 Months of Age, Mongolia, 2015-2021.

Starting in June 2016, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the routine immunization program of Mongolia by using a 2+1 dosing schedule, phased by district. We used prospective hospital surveillance to evaluate the vaccine's effect on pneumonia incidence rates among children 2-59 months of age over a 6-year period. Of 17,607 children with pneumonia, overall adjusted incidence rate ratios showed decreased primary endpoint pneumonia, very severe pneumonia, and probable pneumococcal pneumonia until June 2021. Results excluding and including the COVID-19 pandemic period were similar. Pneumonia declined in 3 districts that introduced PCV13 with catch-up campaigns but not in the 1 district that did not. After PCV13 introduction, vaccine-type pneumococcal carriage prevalence decreased by 44% and nonvaccine-type carriage increased by 49%. After PCV13 introduction in Mongolia, the incidence of more specific pneumonia endpoints declined in children 2-59 months of age; additional benefits were conferred by catch-up campaigns.

Prevalence and Health Associations of Meeting the World Health Organization Guidelines for Physical Activity, Sedentary Behavior, and Sleep in Preschool-Aged Children: The SUNRISE Mongolia Pilot and Feasibility Study.

BACKGROUND: There is a lack of evidence regarding 24-hour movement behaviors of young children from low- and middle-income countries. This study examined Mongolian preschoolers' adherence to the World Health Organization's guidelines for physical activity, sedentary behavior, and sleep; their associations with health indicators, and the feasibility of the SUNRISE International study in Mongolia. METHODS: Preschool-aged children were recruited from 5 kindergartens in urban and rural areas of Ulaanbaatar city and Tuv province in Mongolia. Physical activity and sedentary behavior were measured by an ActiGraph accelerometer worn for 5 consecutive days. Screen time and sleep were reported by parents. The National Institute of Health and Early Years Toolboxes were used to assess motor skills and executive function, respectively. RESULTS: One hundred and one children participated in the study (mean age = 4.82 y, boys = 58), with 88% (n = 89) having complete data for analysis. The proportion of children who met the recommendations for physical activity, sedentary screen time, and sleep was 61%, 23%, and 82%, respectively. Only 7% met all recommendations. Meeting the sleep recommendation individually (P = .032) and in combination with the physical activity recommendation was associated with better gross (P = .019) and fine (P = .042) motor skills. Spending more time in physical activity was positively correlated with motor development. Results confirmed that the SUNRISE study protocol was feasible, age-appropriate, and enjoyable for children. CONCLUSIONS: The results of the SUNRISE pilot study will help inform the SUNRISE Mongolia main study and lay the groundwork for future research into children's 24-hour movement behaviors in Mongolia.

Assessing the contributions of an urban population health initiative to shift political priority towards cardiovascular health: three case studies from Brazil, Mongolia and Senegal.

BACKGROUND: The urban population health initiative was designed as a multidisciplinary, multisector programme to address cardiovascular (CV) disease, specifically hypertension and its underlying causes in the cities of Ulaanbaatar, Mongolia; Dakar, Senegal; and São Paulo, Brazil. This article aims to provide an overview of the history and dynamics of CV disease policy making in the three countries, to present the policy reform contributions of the initiative and its role in the policy agenda-setting framework/process in each country and to identify the enablers and challenges to the initiative for doing so. METHODS: A qualitative case study was conducted for each setting from November 2020 to January 2021, comprised of a document review, semi-structured in-depth interviews and unstructured interviews with stakeholders involved in the initiative. The literature review included documents from the initiative and the peer-reviewed and grey literature with a total of 188 documents screened. Interviews were conducted with 21 stakeholders. Data collection and thematic analysis was guided by (i) the Kingdon multiple streams conceptual framework with the main themes being CV disease problems, policy, politics and the role of policy entrepreneurs; and (ii) the study question inquiring on the role of the urban population health initiative at the CV disease policy level and enabling and challenging factors to advancing CV disease policy. Data were thematically analysed using the Framework Method. RESULTS: Each setting was characterized by a high hypertension and CV disease burden combined with an aware and proactive political environment. Policy outcomes attributed to the initiative were updating the guidelines and/or algorithms of care for hypertension and including revised physical and nutritional education in school curricula, in each city. Overall, the urban health initiative's effects in the policy arena, were most prominent in Mongolia and Senegal, where the team effectively acted as policy entrepreneur, promoting the solutions/policies in alignment with the most pressing local problems and in strong involvement with the political actors. The initiative was also involved in improving access to CV disease drugs at primary health levels. Its success was influenced by the local governance structures, the proximity of the initiative to the policy makers and the local needs. In Brazil, needs were expressed predominantly in the clinical practice. CONCLUSIONS: This multi-country experience shows that, although the policy and political environment plays its role in shaping initiatives, often the local priority needs are the driving force behind wider change.

SARS-CoV-2 Infection in Beaver Farm, Mongolia, 2021.

We report an outbreak of COVID-19 in a beaver farm in Mongolia in 2021. Genomic characterization revealed a unique combination of mutations in the SARS-CoV-2 of the infected beavers. Based on these findings, increased surveillance of farmed beavers should be encouraged.

Anxiety, depression, and brain overwork in the general population of Mongolia.

In Mongolia, there is limited data on the prevalence and correlates of common mental health conditions. This study addresses this data gap by exploring anxiety, depression, and brain overwork. The aim of this study was to determine normative data on these conditions in the general population of Mongolia. This nationwide, population-based, cross-sectional study was conducted in 48 sampling centers across Mongolia in 2020. A total of 613 participants (190 men and 423 women) with a mean age of 41.8 ± 12.4 years were recruited. The participants completed the Hospital Anxiety and Depression Scale (HADS) and the Brain Overwork Scale (BOS-10). Vital signs, body measurements, and lifestyle determinants were also assessed. The prevalence of anxiety was 9.9%, depression was 4.9%, and brain overwork was 18.3% among the participants. Anxiety and depression were correlated with brain overwork symptoms. Brain overwork was associated with young age, unemployment, low income, and alcohol use. These findings suggest that anxiety, depression, and brain overwork are a significant problem in the general population of Mongolia. Further research is needed to develop effective interventions to reduce the prevalence and risk factors of anxiety, depression, and brain overwork.

Home safety hazards associated with unintentional poisoning among children aged 0-5 years in Mongolia: A case-control study.

OBJECTIVE: To examine the association between home safety hazards and unintentional poisoning in children in Mongolia. METHODS: We conducted a case-control study using structured questionnaires to investigate safety behaviours, safety equipment use, and home hazards in households with or without children aged 0-5 years who had suffered from poisoning at home (i.e., cases and controls). We recruited 190 cases (105 medicinal and 84 non-medicinal poisonings, and one each) at the National Center for Maternal and Child Health and 379 controls in the communities between 1 March and 30 October 2021. RESULTS: There were large differences between cases' and controls' households in safety behaviours and home hazards: the failure to store all medicines out of reach of children (68% of cases vs. 25% of controls), the failure to store all medicines safely (out of reach, locked or non-existent) (61% vs. 22%), the failure to put all medicines away immediately after use (77% vs. 43%), the presence of things that a child could climb on to reach high surfaces (82% vs. 67%), the presence of medicines transferred into different containers (28% vs. 9%) and the presence of household products transferred into different containers (28% vs. 16%). These home safety hazards were strongly associated with poisoning after controlling for confounders. CONCLUSION: Children's risk of unintentional poisoning was strongly associated with the unsafe storage of potentially poisonous agents by caregivers and home hazards. Since unsafe storage is widespread, a fail-safe approach such as child-resistant closure of medicines and household products should be considered.

Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Vitamin D supplementation has been shown to increase total hip areal bone mineral density in healthy children and adolescents. We aimed to investigate whether supplementing schoolchildren living in Mongolia with weekly vitamin D3 for 3 years affected fracture risk. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled trial across 18 public schools in Ulaanbaatar, Mongolia. Schoolchildren were eligible if they were aged 6-13 years at screening, had a negative QuantiFERON-TB Gold In-tube assay (QFT) result, were not hypersensitive to vitamin D or immunocompromised, did not use vitamin D supplements, did not have clinical signs of rickets, and had no intention of leaving Ulaanbaatar within 3 years. Participants were randomly assigned (1:1) to receive either vitamin D (oral dose of 14 000 international units [IU] vitamin D3, once per week) or placebo for 3 years using permuted block randomisation stratified by school of attendance. Participants, care providers, and all trial staff were masked to group assignment during the intervention. Prespecified secondary outcomes were incidence of fractures and adverse events, ascertained using questionnaires. The fracture and safety analyses included participants who completed at least one follow-up fracture questionnaire. We estimated adjusted risk ratios (RRs) and 95% CIs using generalised linear models with binomial distribution and a log link function with adjustment for school of attendance. The trial is registered with ClinicalTrials.gov, NCT02276755, and the intervention ended in May, 2019. FINDINGS: Between Sept 2, 2015, and March 20, 2017, 11 475 children were invited to participate in the study and 8851 were recruited and randomly assigned to receive either vitamin D (n=4418) or placebo (n=4433). 8348 participants were included in the fracture and safety analyses (4176 [94·5%] in the vitamin D group and 4172 [94·1%] in the placebo group). Of these, 4125 (49·4%) were female, 4223 (50·6%) were male, and 7701 (92·2%) were of Khalkh ancestry. Median age was 9·2 years (IQR 8·0-10·7) and 7975 (95·5%) participants had baseline serum 25-hydroxyvitamin D concentrations less than 50 nmol/L. During a median follow-up of 3·0 years (IQR 2·9-3·1), 268 (6·4%) participants in the vitamin D group and 253 (6·1%) in the placebo group reported one or more fractures (adjusted RR 1·10, 95% CI 0·93-1·29; p=0·27). Incidence of adverse events did not differ between study groups. INTERPRETATION: Oral vitamin D supplementation at a dose of 14 000 IU/week for 3 years was safe, but did not influence fracture risk in schoolchildren living in Mongolia who had a high baseline prevalence of vitamin D deficiency. FUNDING: US National Institutes of Health.