Effectiveness of a fourth SARS-CoV-2 vaccine dose in previously infected individuals from Austria.

INTRODUCTION: Evidence is limited on the effectiveness of a fourth vaccine dose against coronavirus disease 2019 (COVID-19) in populations with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We estimated the risk of COVID-19 deaths and SARS-CoV-2 infections according to vaccination status in previously infected individuals in Austria. METHODS: This is a nationwide retrospective observational study. We calculated age and gender adjusted Cox proportional hazard ratios (HRs) of COVID-19 deaths (primary outcome) and SARS-CoV-2 infections (secondary outcome) from 1 November to 31 December 2022, primarily comparing individuals with four versus three vaccine doses. Relative vaccine effectiveness (rVE) was calculated as (1-HR) X 100. RESULTS: Among 3,986,312 previously infected individuals, 281,291 (7,1%) had four and 1,545,242 (38.8%) had three vaccinations at baseline. We recorded 69 COVID-19 deaths and 89,056 SARS-CoV-2 infections. rVE for four versus three vaccine doses was -24% (95% CI: -120 to 30) against COVID-19 deaths, and 17% (95% CI: 14-19) against SARS-CoV-2 infections. This latter effect rapidly diminished over time and infection risk with four vaccinations was higher compared to less vaccinated individuals during extended follow-up until June 2023. Adjusted HR (95% CI) for all-cause mortality for four versus three vaccinations was 0.79 (0.74-0.85). DISCUSSION: In previously infected individuals, a fourth vaccination was not associated with COVID-19 death risk, but with transiently reduced risk of SARS-CoV-2 infections and reversal of this effect in longer follow-up. All-cause mortality data suggest healthy vaccinee bias.

Rhabdoid tumors in patients conceived following ART: is there an association?

STUDY QUESTION: In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART? SUMMARY ANSWER: We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT. WHAT IS KNOWN ALREADY: Anecdotal evidence suggests an association of ART with RT. STUDY DESIGN, SIZE, DURATION: This was a multi-institutional retrospective survey. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age). MAIN RESULTS AND THE ROLE OF CHANCE: The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205). LIMITATIONS, REASONS FOR CAUTION: RTs are very rare malignancies and our results are based on a small number of children with RT_ART. WIDER IMPLICATIONS OF THE FINDINGS: This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series. STUDY FUNDING/COMPETING INTEREST(S): M.C.F. is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.10, by the 'Deutsche Forschungsgemeinschaft' DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.05. We declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Male partners' participation in birth preparedness and complication readiness in low- and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Maternal and neonatal health outcomes remain a challenge in low- and middle-income countries (LMICs) despite priority given to involving male partners in birth preparedness and complication readiness (BPCR). Men in LMICs often determine women's access to and affordability of health services. This systematic review and meta-analysis determined the pooled magnitude of male partner's participation in birth preparedness and complication readiness in LMICs. METHODS: Literature published in English language from 2004 to 2019 was retrieved from Google Scholar, PubMed, CINAHL, Scopus, and EMBASE databases. The Joanna Briggs Institute's critical appraisal tool for prevalence and incidence studies were used. A pooled statistical meta-analysis was conducted using STATA Version 14.0. The heterogeneity and publication bias were assessed using the I2 statistics and Egger's test. Duval and Tweedie's nonparametric trim and fill analysis using the random-effect analysis was carried out to validate publication bias and heterogeneity. The random effect model was used to estimate the summary prevalence and the corresponding 95% confidence interval (CI) of birth preparedness and complication readiness. The review protocol has been registered in PROSPERO number CRD42019140752. The PRISMA flow chart was used to show the number of articles identified, included, and excluded with justifications described. RESULTS: Thirty-seven studies with a total of 17, 148 participants were included. The pooled results showed that 42.4% of male partners participated in BPCR. Among the study participants, 54% reported having saved money for delivery, whereas 44% identified skilled birth attendants. 45.8% of male partners arranged transportation and 57.2% of study participants identified health facility as a place of birth. Only 16.1% of the male partners identified potential blood donors. CONCLUSIONS: A low proportion of male partners were identified to have participated in BPCR in LMICs. This calls countries in low- and middle-income setting for action to review their health care policies, to remove the barriers and promote facilitators to male partner's involvement in BPCR. Health systems in LMICs must design and innovate scalable strategies to improve male partner's arrangements for a potential blood donor and transportation for complications that could arise during delivery or postpartum haemorrhage.

Demographic and health surveys showed widening trends in polio immunisation inequalities in Guinea.

AIM: This study examined trends in absolute and relative socio-economic, gender and geographical inequalities in the coverage of polio immunisation in Guinea, West Africa, from 1999 to 2016. METHODS: Data from the 1999, 2005 and 2012 Guinea Demographic and Health Survey and the 2016 Guinea Multiple Indicator Cluster Survey were analysed using the World Health Organization's health equity assessment toolkit. We disaggregated polio immunisation coverage using five equity stratifiers: household economic status, maternal educational level, place of residence, child's gender and region. The four summary measures used were the difference, ratio, population attributable risk and population attributable fraction. A 95% confidence interval (CI) was constructed around point estimates to measure statistical significance. RESULTS: A total of 4778 1-year-old children were included. Polio immunisation coverage in 1999, 2005, 2012 and 2016 were 43.4%, 50.7%, 51.2% and 38.6%, respectively. Socio-economic and geographical inequalities in polio immunisation favoured children with educated mothers who came from richer families living in urban areas. There were also differences in the eight regions over the 1999-2016 study period. CONCLUSION: Targeting children from disadvantaged subgroups must be prioritised to ensure equitable immunisation services that help to eradicate polio in Guinea.

The Jordan Stillbirth and Neonatal Mortality Surveillance (JSANDS) System: Evaluation Study.

BACKGROUND: The Jordan Stillbirth and Neonatal Mortality Surveillance (JSANDS) is an electronic surveillance system that automatically transfers the data on births, stillbirths, and neonatal deaths to the concerned authorities in the Ministry of Health. JSANDS was implemented and tested in 5 maternity hospitals during the period spanning May 2019 through December 2020. OBJECTIVE: This study aimed to evaluate the usefulness and performance of JSANDS to register births, stillbirths, and neonatal deaths, and determine their causes. Specifically, this study examined the JSANDS attributes of acceptability, simplicity, flexibility, stability, representativeness, sustainability, penetration, data quality, sensitivity, and adoption. METHODS: An evaluation study was conducted after 18 months of the JSANDS implementation using the Updated Guidelines for Evaluating Public Health Surveillance Systems. The evaluation focused on how well the system operated to meet its purpose and objectives. The indicators assessing the system attributes were scored on a Likert scale. Each indicator and overall attribute percentage score was represented as score rank and interpreted as excellent (score ≥80%), good (score ≥60 and <80%), average (score ≥40 and <60%), and poor (score <40%). RESULTS: A total of 270 health care professionals participated in this study and evaluated the system performance. The system users rated the usefulness of JSANDS as excellent (percentage score=85.6%). The overall acceptability (percentage score=82.3%), flexibility (percentage score=80.2%), stability (percentage score=80.0%), and representativeness (percentage score=86.6%) were also rated excellent. The overall simplicity was scored good (percentage score=75.4%). All participants were trained on JSANDS and used it in the past 12 months. Of the 270 respondents, 219 (86.2%) reported that they intend to continue using the JSANDS system to register neonatal deaths and stillbirths in the future. All variables in JSANDS had complete data with no missing values. CONCLUSIONS: The performance of JSANDS in registering all stillbirths and neonatal deaths as well as their causes was excellent. Almost all attributes and indicators of JSANDS functionality were rated excellent. JSANDS can be scaled up to cover all maternity hospitals in Jordan. The potential for scaling up the system is very high for many reasons, including its usefulness, simplified stillbirth and neonatal death review tools, and ease of the reporting process.

Structural barriers to knowledge transfer and exchange among men and women in low-, middle- and high-income countries: an international cross-sectional study with vaccine researchers in 44 countries.

BACKGROUND: Globally, women constitute 30% of researchers. Despite an increasing proportion of women in research, they are still less likely to have international collaborations. Literature on barriers to knowledge transfer and exchange (KTE) between men and women remains limited. This study aimed to assess perceived gender barriers to KTE activities in vaccination-related research in low-, middle- and high-income countries. METHODS: This was a cross-sectional data assessment from a self-administered questionnaire distributed to researchers in the field of vaccination research. The administered questionnaire was developed and validated by WHO and McMaster University. Descriptive statistics were carried out. Structural factors of KTE were assessed using 12 statements measured with a five-point Likert scale, ranging from 1 (strongly disagree) to 5 (strongly agree). An index ranging from 12 to 60 points was created to assess structural factors of KTE, with higher score indicating fewer perceived barriers. Multivariable linear regression modelling was applied to examine the association between KTE barriers and gender. RESULTS: A total of 158 researchers were included in the analysis. Regardless of gender and country of affiliation, researchers experienced challenges with respect to KTE activities; particularly factors related to the availability of human and financial resources and level of technical expertise among their target audience. We were also able to identify perceived facilitators among men and women, such as the presence of structures that link researchers and target audiences, the investment of target audiences in KTE efforts and the presence of stable contacts among target audiences. Our linear regression analysis showed that women perceived more barriers than men (R2 = 0.014; B = -1.069; 95% CI -4.035; 1.897). CONCLUSIONS: Men and women shared common perspectives on barriers to KTE. KTE activities could be strengthened by improving structural efforts to reduce gender differences and increase collaborations between researchers and their target audience.

Pediatric bithalamic gliomas have a distinct epigenetic signature and frequent EGFR exon 20 insertions resulting in potential sensitivity to targeted kinase inhibition.

Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown. Here, we identify that bithalamic gliomas harbor frequent mutations in the EGFR oncogene, only rare histone H3 mutation (in contrast to their unilateral counterparts), and a distinct genome-wide DNA methylation profile compared to all other glioma subtypes studied to date. These EGFR mutations are either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain) that occur in the absence of accompanying gene amplification. We find these EGFR mutations are oncogenic in primary astrocyte models and confer sensitivity to specific tyrosine kinase inhibitors dependent on location within the kinase domain or extracellular domain. We initiated treatment with targeted kinase inhibitors in four children whose tumors harbor EGFR mutations with encouraging results. This study identifies a promising genomically-tailored therapeutic strategy for bithalamic gliomas, a lethal and genetically distinct brain tumor of childhood.

The contribution of ketone bodies to glycolytic inhibition for the treatment of adult and pediatric glioblastoma.

PURPOSE: Glioblastoma (GBM) remains one of the most lethal primary brain tumors in children and adults. Targeting tumor metabolism has emerged as a promising-targeted therapeutic strategy for GBM and characteristically resistant GBM stem-like cells (GSCs). METHODS: Gene expression data was obtained from the online patient-histology database, GlioVis. GSC mitochondria morphology was examined by TEM. Cell viability and effect on GSC self-renewal was determined via MTS assay and neurosphere assay, respectively. Proteins were evaluated by Western Blot. RESULTS: Enzymes necessary for ketone catabolism (BDH1, OXCT1 and ACAT1) are significantly downregulated in adult and pediatric GBM. GSC mitochondrial ultrastructure suggested defects in oxidative phosphorylation. Treatment of both GBM and GSC cell lines resulted in dose-dependent decreases in viability in response to glycolytic inhibitor 2-deoxy-D-glucose (2-DG), and ketone body Acetoacetate (AA), but not ß-hydroxybutyrate (ßHB). AA induced apoptosis was confirmed by western blot analysis, indicating robust caspase activation and PARP cleavage. AA reduced neurosphere formation at concentrations as low as 1 mM. Combined treatment of low dose 2-DG (50 µM) with AA resulted in more cell death than either treatment alone. The effect was greater than additive at low concentrations of AA, reducing viability approximately 50% at 1 mM AA. AA was found to directly upregulate mitochondrial uncoupling protein 2 (UCP2), which may explain this potential drug synergism via multi-faceted inhibition of the glycolytic pathway. CONCLUSION: Targeting the metabolic pathway of GBM via glycolytic inhibition in conjunction with ketogenic diet or exogenous ketone body supplementation warrants further investigation as a promising adjunctive treatment to conventional therapy.

Perioperative Management and Outcomes After Cesarean Section-A Cross-Sectional Study From Rural Rwanda.

BACKGROUND: Cesarean sections (c-sections), the most common surgical procedures performed worldwide, are essential in reducing maternal and neonatal deaths. There is a paucity of research studies on c-section care and outcomes in rural African settings. The objective of this study was to describe demographic characteristics, clinical management, and maternal and neonatal outcomes among women receiving c-sections at Kirehe District Hospital (KDH) in rural Rwanda. METHODS: This retrospective cohort study included all women aged ≥ 18 y residing in KDH catchment area who delivered by c-section at KDH between April 1 and September 30, 2017. Demographic and clinical characteristics of these women and their newborns were collected using patient interviews and medical chart extraction. Descriptive analyses were performed, and frequency and percentages are reported. RESULTS: Of the 621 women included in the study, 45.7% (n = 284) were aged 25-34 y; 42.2% (n = 262) were married; 67.5% (n = 419) had primary education; and 75.7% (n = 470) were farmers by occupation. Burundian refugees living in the nearby Mahama Refugee Camp comprised 13.7% (n = 85) of the study population. The most common indication for c-section was having undergone a c-section previously (31.9%, n = 198), followed by acute fetal distress (30.8%, n = 191). Among those with previous c-section as the sole indication for surgery, 85.4% presented as either urgent or emergent cases. Postoperatively, 67.7% spent less than 4 d at the hospital and 96.1% had no postoperative complications before discharge. Approximately 10% (59/572) of neonates were admitted to the neonatal unit, with the most common reason being neonatal infection (59.6%, n = 31). CONCLUSIONS: Our study found that previous delivery via c-section was the primary indication for c-section and that most of these cases were emergent or urgent on presentation. This study highlights the need for further research to explore the feasibility, safety, and appropriateness of vaginal birth after cesarean in rural district hospitals in sub-Saharan Africa.

Falls in older aged adults in 22 European countries: incidence, mortality and burden of disease from 1990 to 2017.

INTRODUCTION: Falls in older aged adults are an important public health problem. Insight into differences in fall-related injury rates between countries can serve as important input for identifying and evaluating prevention strategies. The objectives of this study were to compare Global Burden of Disease (GBD) 2017 estimates on incidence, mortality and disability-adjusted life years (DALYs) due to fall-related injury in older adults across 22 countries in the Western European region and to examine changes over a 28-year period. METHODS: We performed a secondary database descriptive study using the GBD 2017 results on age-standardised fall-related injury in older adults aged 70 years and older in 22 countries from 1990 to 2017. RESULTS: In 2017, in the Western European region, 13 840 per 100 000 (uncertainty interval (UI) 11 837-16 113) older adults sought medical treatment for fall-related injury, ranging from 7594 per 100 000 (UI 6326-9032) in Greece to 19 796 per 100 000 (UI 15 536-24 233) in Norway. Since 1990, fall-related injury DALY rates showed little change for the whole region, but patterns varied widely between countries. Some countries (eg, Belgium and Netherlands) have lost their favourable positions due to an increasing fall-related injury burden of disease since 1990. CONCLUSIONS: From 1990 to 2017, there was considerable variation in fall-related injury incidence, mortality, DALY rates and its composites in the 22 countries in the Western European region. It may be useful to assess which fall prevention measures have been taken in countries that showed continuous low or decreasing incidence, death and DALY rates despite ageing of the population.

The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study.

BACKGROUND: Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017. METHODS: Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning. RESULTS: Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes. CONCLUSIONS: There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.

Indicators to evaluate organisational knowledge brokers: a scoping review.

BACKGROUND: Knowledge translation (KT) is currently endorsed by global health policy actors as a means to improve outcomes by institutionalising evidence-informed policy-making. Organisational knowledge brokers, comprised of researchers, policy-makers and other stakeholders, are increasingly being used to undertake and promote KT at all levels of health policy-making, though few resources exist to guide the evaluation of these efforts. Using a scoping review methodology, we identified, synthesised and assessed indicators that have been used to evaluate KT infrastructure and capacity-building activities in a health policy context in order to inform the evaluation of organisational knowledge brokers. METHODS: A scoping review methodology was used. This included the search of Medline, Global Health and the WHO Library databases for studies regarding the evaluation of KT infrastructure and capacity-building activities between health research and policy, published in English from 2005 to 2016. Data on study characteristics, outputs and outcomes measured, related indicators, mode of verification, duration and/or frequency of collection, indicator methods, KT model, and targeted capacity level were extracted and charted for analysis. RESULTS: A total of 1073 unique articles were obtained and 176 articles were qualified to be screened in full-text; 32 articles were included in the analysis. Of a total 213 indicators extracted, we identified 174 (174/213; 81.7%) indicators to evaluate the KT infrastructure and capacity-building that have been developed using methods beyond expert opinion. Four validated instruments were identified. The 174 indicators are presented in 8 domains based on an adaptation of the domains of the Lavis et al. framework of linking research to action - general climate, production of research, push efforts, pull efforts, exchange efforts, integrated efforts, evaluation and capacity-building. CONCLUSION: This review presents a total of 174 method-based indicators to evaluate KT infrastructure and capacity-building. The presented indicators can be used or adapted globally by organisational knowledge brokers and other stakeholders in their monitoring and evaluation work.

Pediatric and adult H3 K27M-mutant diffuse midline glioma treated with the selective DRD2 antagonist ONC201.

BACKGROUND: H3 K27M-mutant diffuse midline glioma is a fatal malignancy with no proven medical therapies. The entity predominantly occurs in children and young adults. ONC201 is a small molecule selective antagonist of dopamine receptor D2/3 (DRD2/3) with an exceptional safety profile. Following up on a durable response in the first H3 K27M-mutant diffuse midline glioma patient who received ONC201 (NCT02525692), an expanded access program was initiated. METHODS: Patients with H3 K27M-mutant gliomas who received at least prior radiation were eligible. Patients with leptomeningeal spread were excluded. All patients received open-label ONC201 orally once every week. Safety, radiographic assessments, and overall survival were regularly assessed at least every 8 weeks by investigators. As of August 2018, a total of 18 patients with H3 K27M-mutant diffuse midline glioma or DIPG were enrolled to single patient expanded access ONC201 protocols. Among the 18 patients: seven adult (> 20 years old) and seven pediatric (< 20 years old) patients initiated ONC201 with recurrent disease and four pediatric patients initiated ONC201 following radiation, but prior to disease recurrence. FINDINGS: Among the 14 patients with recurrent disease prior to initiation of ONC201, median progression-free survival is 14 weeks and median overall survival is 17 weeks. Three adults among the 14 recurrent patients remain on treatment progression-free with a median follow up of 49.6 (range 41-76.1) weeks. Among the 4 pediatric patients who initiated adjuvant ONC201 following radiation, two DIPG patients remain progression-free for at least 53 and 81 weeks. Radiographic regressions, including a complete response, were reported by investigators in a subset of patients with thalamic and pontine gliomas, along with improvements in disease-associated neurological symptoms. INTERPRETATION: The clinical outcomes and radiographic responses in these patients provide the preliminary, and initial clinical proof-of-concept for targeting H3 K27M-mutant diffuse midline glioma with ONC201, regardless of age or location, providing rationale for robust clinical testing of the agent.

Risk factors for stunting among children under five years: a cross-sectional population-based study in Rwanda using the 2015 Demographic and Health Survey.

BACKGROUND: Child growth stunting remains a challenge in sub-Saharan Africa, where 34% of children under 5 years are stunted, and causing detrimental impact at individual and societal levels. Identifying risk factors to stunting is key to developing proper interventions. This study aimed at identifying risk factors of stunting in Rwanda. METHODS: We used data from the Rwanda Demographic and Health Survey (DHS) 2014-2015. Association between children's characteristics and stunting was assessed using logistic regression analysis. RESULTS: A total of 3594 under 5 years were included; where 51% of them were boys. The prevalence of stunting was 38% (95% CI: 35.92-39.52) for all children. In adjusted analysis, the following factors were significant: boys (OR 1.51; 95% CI 1.25-1.82), children ages 6-23 months (OR 4.91; 95% CI 3.16-7.62) and children ages 24-59 months (OR 6.34; 95% CI 4.07-9.89) compared to ages 0-6 months, low birth weight (OR 2.12; 95% CI 1.39-3.23), low maternal height (OR 3.27; 95% CI 1.89-5.64), primary education for mothers (OR 1.71; 95% CI 1.25-2.34), illiterate mothers (OR 2.00; 95% CI 1.37-2.92), history of not taking deworming medicine during pregnancy (OR 1.29; 95%CI 1.09-1.53), poorest households (OR 1.45; 95% CI 1.12-1.86; and OR 1.82; 95%CI 1.45-2.29 respectively). CONCLUSION: Family-level factors are major drivers of children's growth stunting in Rwanda. Interventions to improve the nutrition of pregnant and lactating women so as to prevent low birth weight babies, reduce poverty, promote girls' education and intervene early in cases of malnutrition are needed.

Community-based self-collected human papillomavirus screening in rural Zimbabwe.

BACKGROUND: In low- and middle-income countries (LMIC), women have limited access to and uptake of cervical cancer screening. Delayed diagnosis leads to poorer outcomes and early mortality, and continues to impede cancer control disproportionately in LMIC. Integrating self-collected, community-based screening for High Risk-Human Papilloma Virus (HR-HPV) into existent HIV programs is a potential screening method to identify women at high risk for developing high-risk cervical lesions. METHODS: We implemented community-based cross-sectional study on self-collection HR-HPV screening in conjunction with existing community outreach models for the distribution of antiretroviral therapy (ART) and the World Health Organization Expanded Program on Immunization (EPI) outreach in villages in rural Zimbabwe from January 2017 through May 2017. RESULTS: Overall, there was an 82% response rate: 70% of respondents participated in self-collection and 12% were ineligible for the study (inclusion criteria: age 30-65, not pregnant, with an intact uterus). Women recruited in the first 2-3 months of the study had more opportunities to participate and therefore significantly higher participation: 81% participation (additional 11% ineligible), while those with fewer opportunities also had lower participation: 63% (additional 13% ineligible) (p < 0.001). Some village outreach centers (N = 5/12) had greater than 89% participation. CONCLUSIONS: Integration of HR-HPV screening into existing community outreach models for HIV and immunizations could facilitate population-based screening to scale cancer control and prevention programs in sub-Saharan Africa. Community/village health workers (CHW/VHW) and village outreach programs offer a potential option for cervical cancer screening programs to move towards improving access of sexual and reproductive health resources for women at highest risk.

Lions Quest Skills for Adolescence Program as a School Intervention to Prevent Substance Use-a Pilot Study Across Three South East European Countries.

Development of personal and social skills in a classroom prevents later drug use and alcohol abuse, and influence-related risk factors. However, clinical trials on the potential impact of such programs from low- or middle-income countries remain limited. Lions Quest Skills for Adolescence (LQSFA), a school-based prevention intervention supporting life skills, was implemented in three South East European countries. This was a collaboration between the United Nations Office on Drugs and Crime, the Lions Clubs International Foundation, and the Ministries of Education of Serbia, the Former Yugoslav Republic of Macedonia and Montenegro. The pilot was a multisite non-randomized trial. A total of 2964 elementary school students received the intervention through 232 instructors trained by the same internationally certified trainer. These were compared to 2232 students following the regular curriculum, which does not include LQFSA, in the same elementary schools. The assessment was done at the beginning and at the end of the same academic year (period of 10 months). Despite limited fluctuations, the overall results indicated an encouraging outcome on the current use of substances (alcohol, cigarettes, and marijuana) as well as intention to using these substances in the next 3 months among current users. This study attempts to address this aforementioned gap in literature and contributes to the body of research demonstrating the value, feasibility, and transferability of life skills programs in achieving prevention outcomes in South East Europe. Moreover, it paves the way to a future randomized clinical trial to further corroborate the results, overcoming limitation in current study design.

Three versus five lumbar paravertebral injections for inguinal hernia repair in the elderly: a randomized double-blind clinical trial.

PURPOSE: The objective of the study was to compare three nerve stimulator-guided paravertebral injections versus five injections for elderly patients undergoing inguinal hernia repair in terms of the amount of intraoperative fentanyl and propofol consumption and conversion to general anesthesia. The secondary objective was postoperative pain. METHODS: A prospective, randomized, double-blind clinical trial was performed. 200 elderly patients undergoing unilateral herniorrhaphy were randomized into two groups. Group III received three PVB injections from T12 to L2 and placebo at T11 and L3. Group V received five PVB injections from T11 to L3. RESULTS: The mean intraoperative fentanyl and propofol consumption were significantly lower in group V (4.9 ± 7.2 µg versus 20.0 ± 12.9 µg and 5.7 ± 11.6 mg versus 34.6 ± 22.9 mg, respectively, p value < 0.0001). Five patients (5.0%) in group III had failed block and were converted to general anesthesia (p value = 0.024). Group V had significantly lower pain scores compared to group III during the first three postoperative days (p value < 0.0001). CONCLUSION: The five PVB injection technique is more suitable as a sole anesthetic technique for elderly patients undergoing herniorrhaphy, since it required less intraoperative supplemental analgesia and provided lower postoperative pain scores compared to the three PVB injection technique. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02537860.

Factors associated with condom use and HIV testing among young men who have sex with men: a cross-sectional survey in a random online sample in Sweden.

OBJECTIVES: The objectives are to analyse social determinants of sexual health behaviour (condom use and HIV testing) among young, internet-active, cis men who have sex with men (MSM) in a high-income country. The aspects of sexual health behaviour analysed here are condomless anal intercourse with one or more new or casual partner(s), condomless anal intercourse during the most recent sex with a man and HIV testing. METHODS: A randomised sample of men active on Sweden's main online community for Lesbian, Gay, Bisexual and Trans people responded to an online survey (response rate 19%). A subsample of young people, aged 15-29, was analysed (effective sample 597-669) using multivariable logistic regression with respect to factors associated with condomless anal intercourse with one or more new or casual partner(s), condomless anal intercourse at most recent sex and not having had a test for HIV. RESULTS: Low education, being single and living in a metropolitan area were found to be independently associated with condomless anal intercourse with new or casual partner(s). Sex with a steady partner was associated with condomless anal intercourse during the most recent sex. Knowledge of where to get tested, high education, being born outside Sweden and condomless anal intercourse with new or casual sex partner(s) were independently associated with having been tested for HIV. CONCLUSIONS: The factors associated with sexual health behaviour among young MSM are complex, and preventive messages need to be tailored accordingly.

Factors for incomplete adherence to antiretroviral therapy including drug refill and clinic visits among older adults living with human immunodeficiency virus - cross-sectional study in South Africa.

OBJECTIVES: To assess adherence outcomes to antiretroviral therapy (ART) of recipients ≥50 years in Soweto, South Africa. METHODS: This was a secondary data analysis for a cross-sectional study at two HIV clinics in Soweto. Data on ART adherence and covariates were gathered through structured interviews with HIV 878 persons living with HIV (PLHIV) receiving ART. Logistic regression analysis was used to assess associations. RESULTS: PLHIV ≥50 years (n = 103) were more likely to miss clinic visits during the last six months than PLHIV aged 25-49 (OR 2.15; 95%CI 1.10-4.18). PLHIV ≥50 years with no or primary-level education were less likely to have missed a clinic visit during the last six months than PLHIV with secondary- or tertiary-level education in the same age category (OR 0.3; 95%CI 0.1-1.1), as were PLHIV who did not disclose their status (OR 0.2; 95%CI 0-1.1). There was no evidence of increased risk for non-adherence to ART pills and drug refill visits among older PLHIV. CONCLUSION: Missing a clinic visit was more common among older PLHIV who were more financially vulnerable. Further studies are needed to verify these findings and identify new risk factors associated with ART adherence.

Sex differences and risk factors for diabetes mellitus - an international study from 193 countries.

BACKGROUND: Increases in overweight and obesity among youths have resulted in the diagnosis of Type 2 diabetes mellitus (T2DM) at earlier ages. The impact of lifestyle-related factors has been implicated; however, its relation to morbidity and mortality and sex differences remain unclear. We aimed to document the changes in risk factors and sex differences associated with T2DM-related morbidity and mortality during 1995-2015. METHOD: We used mortality rates and morbidity estimates from the Global Burden of Diseases Study 2016 using Disability-Adjusted Life Years (DALY). Multiple linear regression analyses were used to determine associations between T2DM-related mortality and related risk factors. DALYs were grouped by country income level, and were stratified by sex. RESULTS: Increases in mortality were observed for both sexes, and females tended to have higher mortality rates per 100,000 persons. Body mass index (BMI) continued to be the leading risk factor for T2DM-related mortality, and increases in BMI were more common in low- and middle-income countries (LIC and MIC). Low physical activity was strongly associated with mortality rates, followed by dietary risks and smoking (2.4; 1.4; 0.8 per 100,000 persons, respectively). Similar patterns were observed after adjustments for income level, sex, and age. DALYs continued to show increasing trends across all income levels during 1995-2015 (high-income (HIC):16%; MIC: 36%; LIC: 12%). Stratification by sex showed similar results; males had fewer T2DM DALYs than females, though a greater increase was observed among males. CONCLUSION: Overall, T2DM related mortality was higher among females. Compared to in HIC, there appeared to be a considerable increase in the burden of T2DM in MIC and LIC, where BMI is the leading risk factor for T2DM-related mortality. Prevention programs should emphasize related risk factors according to the existing standard of care.