No benefit from TMZ treatment in GB with truly unmethylated MGMT promoter: Reanalysis of the CE.6 and the pooled Nordic/NOA-08 trials in elderly GB patients.

BACKGROUND: The treatment of elderly/ frail patients with glioblastoma is a balance between avoiding undue toxicity, while not withholding effective treatment. It remains debated, whether these patients should receive combined chemo-radiotherapy with temozolomide (RT/TMZ➜TMZ) regardless of the O6-methylguanine DNA methyltransferase gene promoter (MGMTp) methylation status. MGMT is a well-known resistance factor blunting the treatment effect of TMZ, by repairing the most genotoxic lesion. Epigenetic silencing of the MGMTp sensitizes glioblastoma to TMZ. For risk adapted treatment, it is of utmost importance to accurately identify patients, who will not benefit from TMZ treatment. METHODS: Here, we present a reanalysis of the clinical trials CE.6 and the pooled NOA-08 and Nordic trials in elderly glioblastoma patients that compared RT to RT/TMZ➜TMZ, or RT to TMZ, respectively. For 687 patients with available MGMTp methylation data, we applied a cutoff discerning truly unmethylated glioblastoma, established in a pooled analysis of four clinical trials for glioblastoma, with RT/TMZ➜TMZ treatment, using the same quantitative methylation specific MGMTp PCR assay. RESULTS: When applying this restricted cutoff to the elderly patient population, we confirmed that glioblastoma with truly unmethylated MGMTp derived no benefit from TMZ treatment. In the Nordic/NOA-08 trials RT was better than TMZ, suggesting little or no benefit from TMZ. CONCLUSION: For evidence-based treatment of glioblastoma patients validated MGMTp methylation assays should be used that accurately identify truly unmethylated patients. Respective stratified management of patients will reduce toxicity without compromising outcome and allow testing of more promising treatment options.

Association between malaria and household air pollution interventions in a predominantly rural area of Ghana.

BACKGROUND: Though anecdotal evidence suggests that smoke from HAP has a repellent effect on mosquitoes, very little work has been done to assess the effect of biomass smoke on malaria infection. The study, therefore, sought to investigate the hypothesis that interventions to reduce household biomass smoke may have an unintended consequence of increasing placental malaria or increase malaria infection in the first year of life. METHODS: This provides evidence from a randomized controlled trial among 1414 maternal-infant pairs in the Kintampo North and Kintampo South administrative areas of Ghana. Logistic regression was used to assess the association between study intervention assignment (LPG, Biolite or control) and placental malaria. Finally, an extended Cox model was used to assess the association between study interventions and all episodes of malaria parasitaemia in the first year of infant's life. RESULTS: The prevalence of placental malaria was 24.6%. Out of this, 20.8% were acute infections, 18.7% chronic infections and 60.5% past infections. The study found no statistical significant association between the study interventions and all types of placental malaria (OR = 0.88; 95% CI 0.59-1.30). Of the 1165 infants, 44.6% experienced at least one episode of malaria parasitaemia in the first year of life. The incidence of first and/or only episode of malaria parasitaemia was however found to be similar among the study arms. CONCLUSION: The findings suggest that cookstove interventions for pregnant women and infants, when combined with additional malaria prevention strategies, do not lead to an increased risk of malaria among pregnant women and infants.

Poor early childhood growth is associated with impaired lung function: Evidence from a Ghanaian pregnancy cohort.

OBJECTIVES: Nearly 40% of African children under 5 are stunted. We leveraged the Ghana randomized air pollution and health study (GRAPHS) cohort to examine whether poorer growth was associated with worse childhood lung function. STUDY DESIGN: GRAPHS measured infant weight and length at birth and 3, 6, 9,12 months, and 4 years of age. At age 4 years, n = 567 children performed impulse oscillometry. We employed multivariable linear regression to estimate associations between birth and age 4 years anthropometry and lung function. Next, we employed latent class growth analysis (LCGA) to generate growth trajectories through age 4 years. We employed linear regression to examine associations between growth trajectory assignment and lung function. RESULTS: Birth weight and age 4 weight-for-age and height-for-age z-scores were inversely associated with airway resistance (e.g., R5 , or total airway resistance: birth weight ß = -0.90 cmH2O/L/s, 95% confidence interval [CI]: -1.64, -0.16 per 1 kg increase; and R20 , or large airway resistance: age 4 height-for-age ß = -0.40 cmH2O/L/s, 95% CI: -0.57, -0.22 per 1 unit z-score increase). Impaired growth trajectories identified through LCGA were associated with higher airway resistance, even after adjusting for age 4 body mass index. For example, children assigned to a persistently stunted trajectory had higher R5 (ß = 2.71 cmH2O/L/s, 95% CI: 1.07, 4.34) and R20 (ß = 1.43 cmH2O/L/s, 95% CI: 0.51, 2.36) as compared to normal. CONCLUSION: Children with poorer anthropometrics through to age 4 years had higher airway resistance in early childhood. These findings have implications for lifelong lung health, including pneumonia risk in childhood and reduced maximally attainable lung function in adulthood.

Profile and predictors of adolescent tobacco use in Ghana: evidence from the 2017 Global Youth Tobacco Survey (GYTS).

BACKGROUND: Understanding the predictive factors for tobacco use, and initiation among the youth is critical for effective intervention and prevention. We, therefore, aimed to determine the profile, associated factors, the regional disparities in the use of tobacco products among the youth in Ghana. METHOD: The study used the 2017 Ghana Global Youth Tobacco Survey (GYTS) to obtain tobacco-related information among the youth in Junior High Schools across the country. The survey used a two-stage cluster randomized sampling technique to obtain nationally representative data. Weighted univariate and multivariate logistic regression analyses were used to assess the association of participant's characteristics and use of tobacco. RESULTS: Out of the 6039 targeted respondents, 5,664 (93.8%) participated, 2,707 males, 2,929 females, and 28 of the participants had missing gender data. The use of any tobacco product (cigarette, smokeless tobacco, electronic cigarette, or waterpipe tobacco) was 28.3, 7.0, and 4.8% in the Savanna/northern zone, middle/forest zone, and Coastal zone respectively. From the univariate analysis, age (p = 0.005), pocket money (p < 0.001), and exposure to secondhand smoke (SHS) at home (p < 0.001) were significantly associated with tobacco use. In the multivariate analysis, age (p = 0.002), pocket money (p < 0.001), exposure to SHS at home (p < 0.001), and being taught about the dangers of tobacco use (p = 0.043) were significantly associated with tobacco use. CONCLUSION: Multiple factors including age, pocket money, exposure to SHS were identified to be associated with tobacco use among the youth in Ghana. Promoting anti-smoking campaigns in early adolescence, as well as programmes targeting early tobacco use can guard the youth against initiating tobacco use.

Prenatal and Postnatal Household Air Pollution Exposure and Infant Growth Trajectories: Evidence from a Rural Ghanaian Pregnancy Cohort.

BACKGROUND: The exposure-response association between prenatal and postnatal household air pollution (HAP) and infant growth trajectories is unknown. OBJECTIVES: To evaluate associations between prenatal and postnatal HAP exposure and stove interventions on growth trajectories over the first year of life. METHODS: The Ghana Randomized Air Pollution and Health Study enrolled n=1,414 pregnant women at ≤24wk gestation from Kintampo, Ghana, and randomized them to liquefied petroleum gas (LPG), improved biomass, or open fire (control) stoves. We quantified HAP exposure by repeated, personal prenatal and postnatal carbon monoxide (CO) and, in a subset, fine particulate matter [PM with an aerodynamic diameter of ≤2.5µm (PM2.5)] assessments. Length, weight, mid-upper arm circumference (MUAC) and head circumference (HC) were measured at birth, 3, 6, 9, and 12 months; weight-for-age, length-for-age (LAZ), and weight-for-length z (WLZ)-scores were calculated. For each anthropometric measure, we employed latent class growth analysis to generate growth trajectories over the first year of life and assigned each child to a trajectory group. We then employed ordinal logistic regression to determine associations between HAP exposures and growth trajectory assignments. Associations with stove intervention arm were also considered. RESULTS: Of the 1,306 live births, 1,144 had valid CO data and anthropometric variables measured at least once. Prenatal HAP exposure increased risk for lower length [CO odds ratio (OR)= 1.17, 95% CI: 1.01, 1.35 per 1-ppm increase; PM2.5 OR= 1.07, 95% CI: 1.02, 1.13 per 10-µg/m3 increase], lower LAZ z-score (CO OR= 1.15, 95% CI: 1.01, 1.32 per 1-ppm increase) and stunting (CO OR= 1.25, 95% CI: 1.08, 1.45) trajectories. Postnatal HAP exposure increased risk for smaller HC (CO OR= 1.09, 95% CI: 1.04, 1.13 per 1-ppm increase), smaller MUAC and lower WLZ-score (PM2.5 OR= 1.07, 95% CI: 1.00, 1.14 and OR= 1.09, 95% CI: 1.01, 1.19 per 10-µg/m3 increase, respectively) trajectories. Infants in the LPG arm had decreased odds of having smaller HC and MUAC trajectories as compared with those in the open fire stove arm (OR= 0.58, 95% CI: 0.37, 0.92 and OR= 0.45, 95% CI: 0.22, 0.90, respectively). DISCUSSION: Higher early life HAP exposure (during pregnancy and through the first year of life) was associated with poorer infant growth trajectories among children in rural Ghana. A cleaner-burning stove intervention may have improved some growth trajectories. https://doi.org/10.1289/EHP8109.

Prenatal and Postnatal Household Air Pollution Exposures and Pneumonia Risk: Evidence From the Ghana Randomized Air Pollution and Health Study.

BACKGROUND: Nearly 40% of the world's population is exposed daily to household air pollution. The relative impact of prenatal and postnatal household air pollution exposure on early childhood pneumonia, a leading cause of mortality, is unknown. RESEARCH QUESTION: Are prenatal or postnatal household air pollution, or both, associated with pneumonia risk in the first year of life? STUDY DESIGN AND METHODS: The Ghana Randomized Air Pollution and Health Study enrolled 1,414 nonsmoking, pregnant women before 24 weeks' gestation with prospective follow-up to the child's age of 1 year. We measured 72-h personal household air pollution exposures, indexed by carbon monoxide (CO), four times prenatally and three times postnatally. Weekly fieldworker surveillance identified ill-appearing children for physician pneumonia assessment. We used quasi-Poisson models to examine associations between prenatal and postnatal CO and physician-diagnosed pneumonia and severe pneumonia. Sex-specific effects were examined. RESULTS: Of the 1,306 live births, 1,141 infants were followed up with 55,605 child-weeks of fieldworker surveillance. The estimated risk for pneumonia and severe pneumonia in the first year of life increased by 10% (relative risk [RR], 1.10; 95% CI, 1.04-1.16) and 15% (RR, 1.15; 95% CI, 1.03-1.28), respectively, per 1-part per million (ppm) increase in average prenatal CO exposure and by 6% (RR, 1.06; 95% CI, 0.99-1.13) per 1-ppm increase in average postnatal CO exposure. Sex-stratified analyses suggest that in girls, higher prenatal CO exposure was associated with pneumonia risk, while no association was seen in boys. INTERPRETATION: Prenatal household air pollution exposure increased risk of pneumonia and severe pneumonia in the first year of life. Clean-burning interventions may be most effective when begun prenatally. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01335490; URL: www.clinicaltrials.gov.

Open defecation and attainment of Sustainable Development Goal Six: evidence from Kintampo Surveillance System, Ghana.

Objective: This study examined whether the open-defecation (OD) free target is achievable by 2030. Design: Longitudinal study. Setting: Seven sub-Districts of Kintampo North Municipal, and five sub-Districts of Kintampo South District. Data source: Kintampo health and demographic surveillance system. Participants: Data was collected from household heads or their representatives over a 12-year period from 2005 to 2016. Main outcome: Open-defecation and attainment of OD free by 2030. Results: In an exploratory analysis, the correlation between the total number of households, year, and total number of OD households was obtained. The average percentage yearly increase or decrease in OD was computed and used to project the percentage of OD for the years 2020, 2025 and 2030. In addition, geo-spatial technology was used to visualize variability in OD across the twelve sub-Districts. The results showed that the OD free target is not achievable in 2030 or even if the current trend continues. In 2016, 44.2 per cent of the 31,571 households defecated openly. In six out of the 12 sub-Districts, more than half of the households openly defecated. Four out of these six sub-Districts were in the Kintampo North Municipality. Conclusion: The 2030 OD free target is not achievable in the Kintampo districts of Ghana if the current trend continues. Funding: Kintampo Health Research Centre funded this work.

Blood Lead Levels among Blood Donors and High-Risk Occupational Groups in a Mining Area in Ghana: Implications for Blood Transfusion among Vulnerable Populations.

Lead poisoning has been a major global health problem for decades, and blood transfusion has been suspected as a neglected potential source of lead exposure. Children and pregnant women are most vulnerable to the toxic effects of lead and over 40 percent of blood transfused in Ghana is given to children under 5 years. However, there is little data on the levels of lead in donor blood and the main sources of lead exposure in the Ghanaian population. This study compared blood lead levels (BLL) among selected occupations at risk of lead exposure with healthy blood donors in nonexposed occupations in a Ghanaian mining area. We enrolled 40 participants each from the following high-risk occupational groups: small scale miners, painters/sprayers, drivers/fuel station attendants, and auto-mechanics as well as 40 healthy blood donors (made up of teachers, traders, and office workers). One millilitre of blood was collected from each participant for determination of their BLL, haemoglobin concentration, and blood film morphology. A total of 200 participants made up of 186 (93%) males and 14 (7%) females were enrolled. The mean age of participants was 28.6 ± 8.2 years and their geometric mean (GM) BLL was 6.3 GSD 1.4 µg/dL [95% CI: 6.0 - 6.6]. Participants in high risk occupations had significantly higher GM BLL of 6.7 µg/dL [95% CI :6.4-7.0] compared to 5.0 µg/dL [95% CI: 4.4-5.7] for healthy blood donors [p < 0.001]. The prevalence of elevated BLL (≥5 µg/dL) among the entire study participants, high risk occupations and blood donors was 84.5%, 89.4% and 65% respectively. There was significant association between elevated BLLs and working in an at-risk occupational group [aOR = 3.58, p = 0.014]. Haemoglobin concentration was not significantly associated with elevated BLLs. Basophilic stippling was not observed in any of the blood smears. Blood lead levels were high in blood donors and at-risk occupations in the study area and occupation was associated with elevated BLLs. It is important that measures to safeguard the integrity of donor blood go beyond screening for infectious diseases to include screening individuals in high-risk occupations for lead and other heavy metals to ensure that donor blood from such individuals is safe and does not pose potential danger to the health of vulnerable populations such as children and pregnant women.

Waterpipe use among the youth in Ghana: Lessons from the Global Youth Tobacco Survey (GYTS) 2017.

INTRODUCTION: The Global Youth Tobacco Survey's findings have been used to support Ghana's tobacco control legislation, monitor tobacco use among the youth and also used in meeting various Articles of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC). These Articles include: Article 8 (Protection for exposure to tobacco smoke); Article 12 (Education, communication, training and public awareness); Article 13 (Tobacco advertising, promotion, and sponsorship); Article 14 (Demand reduction measures concerning tobacco dependence and cessation); and Article 16 (Sales to and by minors). Among the four waves of GYTS in Ghana, the 2017 GYTS was the first to assess waterpipe smoking, through optional questions included in the GYTS questionnaire. We assessed sex, age and regional differentials in waterpipe smoking among the youth in Ghana, and also explored the association between the use of other tobacco products and waterpipe use. METHODS: The GYTS employs a standardized methodology with self-administered questionnaires, consisting of core, optional, and country specific questions. Fourteen questions, out of the seventy-four (74) questions administered for the entire GYTS, assessed waterpipe tobacco smoking (WTS). Chi-squared test was used to assess sex, age, grade/form and regional differentials in waterpipe use. Furthermore, the association between smoking cigarettes, smokeless tobacco, electronic cigarettes and waterpipe smoking, was explored by employing a chi-squared test with a 5% significance level. RESULTS: Of a total of 5664 students who participated in the study, 90.9% were aged 13-15 years. The respondents were almost equally distributed among males and females. Overall, 3.1% of the respondents had ever smoked waterpipe. The overall prevalence of current waterpipe use was 1.7%; with 2.1% in girls (95% CI: 0.9-4.7%) and 0.9% in boys (95% CI: 0.5-1.6%), p=0.033. Additionally, more than half (55.0%) of the current waterpipe users smoked three or more sessions per day. Surprisingly, close to half (46.9%) of the current waterpipe users smoked at home. CONCLUSIONS: Waterpipe use, particularly among the female student population, represents an emerging tobacco epidemic and hence deserves immediate attention from authorities. This study revealed that waterpipe is being used among Junior High students in Ghana. Education on the health implications of waterpipe use should be intensified among the youth, to help minimize its use and to prevent its associated health harms.