Identifying contextual determinants of problems in tuberculosis care provision in South Africa: a theory-generating case study.

BACKGROUND: Despite progress towards End TB Strategy targets for reducing tuberculosis (TB) incidence and deaths by 2035, South Africa remains among the top ten high-burden tuberculosis countries globally. A large challenge lies in how policies to improve detection, diagnosis and treatment completion interact with social and structural drivers of TB. Detailed understanding and theoretical development of the contextual determinants of problems in TB care is required for developing effective interventions. This article reports findings from the pre-implementation phase of a study of TB care in South Africa, contributing to HeAlth System StrEngThening in Sub-Saharan Africa (ASSET)-a five-year research programme developing and evaluating health system strengthening interventions in sub-Saharan Africa. The study aimed to develop hypothetical propositions regarding contextual determinants of problems in TB care to inform intervention development to reduce TB deaths and incidence whilst ensuring the delivery of quality integrated, person-centred care. METHODS: Theory-building case study design using the Context and Implementation of Complex Interventions (CICI) framework to identify contextual determinants of problems in TB care. Between February and November 2019, we used mixed methods in six public-sector primary healthcare facilities and one public-sector hospital serving impoverished urban and rural communities in the Amajuba District of KwaZulu-Natal Province, South Africa. Qualitative data included stakeholder interviews, observations and documentary analysis. Quantitative data included routine data on sputum testing and TB deaths. Data were inductively analysed and mapped onto the seven CICI contextual domains. RESULTS: Delayed diagnosis was caused by interactions between fragmented healthcare provision; limited resources; verticalised care; poor TB screening, sputum collection and record-keeping. One nurse responsible for TB care, with limited integration of TB with other conditions, and policy focused on treatment adherence contributed to staff stress and limited consideration of patients' psychosocial needs. Patients were lost to follow up due to discontinuity of information, poverty, employment restrictions and limited support for treatment side-effects. Infection control measures appeared to be compromised by efforts to integrate care. CONCLUSIONS: Delayed diagnosis, limited psychosocial support for patients and staff, patients lost to follow-up and inadequate infection control are caused by an interaction between multiple interacting contextual determinants. TB policy needs to resolve tensions between treating TB as epidemic and individually-experienced social problem, supporting interventions which strengthen case detection, infection control and treatment, and also promote person-centred support for healthcare professionals and patients.

Intake of dietary fibre, red and processed meat and risk of late-onset Chronic Inflammatory Diseases: A prospective Danish study on the "diet, cancer and health" cohort.

Background: Human and animal studies support the involvement of diet in the development of CID -chronic inflammatory diseases such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, psoriatic arthritis, and multiple sclerosis. Objective: This cohort study aimed to investigate the association between intake of fibre, red and processed meat, and occurrence of late-onset CID (50+ years of age) in the DCH: Danish Diet, Cancer and Health cohort. We hypothesised that risk of late-onset CID would be lower among those with high intake of fibre and/or low intake of meat compared to individuals with low fibre and/or high meat intake. Methods: The DCH recruited 56,468 individuals, aged 50-64 years, between 1993 and 1997. At recruitment, diet intake was registered using food frequency questionnaires as well as lifestyle factors in 56,075 persons. Exposure variables were generated as sex-adjusted tertiles of fibre and meat (g/day). Development of CIDs was identified in national registries. Hazard ratios (HR) of late-onset CIDs (adjusted for age, sex, energy intake, alcohol, smoking, education, comorbidity, and civil status) were estimated for all three exposure variables. Results: During follow-up of 1,123,754 years (median (Interquartile range) = 22.2 (20.1-23.1)), 1,758 (3.1%) participants developed at least one CID. The adjusted HRs for developing CID (low fibre 1.04 [0.89-1.22] and medium fibre 1.04 [0.91-1.18] (high fibre as reference), and medium meat 0.96 [0.86-1.09] and high meat 0.94 [0.82-1.07] (low meat as reference)) or the individual diseases were not statistically significant. Conclusion: This large study did not support that a high intake of fibre and/or a low intake of meat had a high impact on the risk of late-onset CID.

Performance management in primary healthcare: Nurses' experiences.

BACKGROUND: The use of the performance management (PM) system is highly contested by public servants in South Africa, although its value as essential to the appraisal and management of staff is undeniable. OBJECTIVES: The aim of this study was to explore nurses' perceptions and experiences of the PM system at primary healthcare (PHC) facilities in relation to the current health system's reforms. METHOD: An exploratory, descriptive and qualitative design was utilised. Participants were selected through purposive sampling. A semi-structured interview tool was used to collect data from 18 nurses in four sub-districts of Dr. Kenneth Kaunda district in the North West province. Data were analysed through thematic analysis. RESULTS: The findings of this study confirmed that PM is implemented to some extent. However, various loopholes in its implementation threaten the accuracy and transparency of the system and leave it vulnerable to perceived organisational injustice and unfairness, with the objectivity of the system questioned. The limitations of the current PM system revealed by this study include (1) the lack of alignment with current health system reforms towards comprehensive and integrated care that demands person-centred care; (2) the system's usefulness for career progression, performance improvement and rewarding exceptional performance. CONCLUSION: Performance management is inadequately applied in PHC facilities at district level and needs to be realigned to include the appraisal of key attributes required for the current health system's reforms towards comprehensive and integrated care, including the provision of person-centred care, which is central for responding adequately to South Africa's changing disease profile towards multi-morbidity.

Indicators for routine monitoring of effective mental healthcare coverage in low- and middle-income settings: a Delphi study.

High-quality information to measure the need for, and the uptake, cost, quality and impact of care is essential in the pursuit of scaling up mental health care in low- and middle-income countries (LMIC). The aim of this study was to identify indicators for the measurement of effective coverage of mental health treatment. We conducted a two-round Delphi study (n = 93 experts from primarily LMIC countries Ethiopia, India, Nepal, Nigeria, South Africa and Uganda), in order to generate and prioritize a set of indicators. First, 52 unique indicators were generated (based on a total of 876 responses from participants). Second, the selected indicators were then scored for significance, relevance and feasibility. Mean priority scores were calculated per indicator (score range, 1-5). All 52 indicators had a weighted mean score that ranged from 3.20 for the lowest ranked to 4.27 for the highest ranked. The 15 highest ranked indicators cover the different domains of measuring effective mental health treatment coverage. This set of indicators is highly stable between the different groups of experts, as well as between the different participating countries. This study provides data on how mental health service and financial coverage can be assessed in LMIC. This is an important element in the move to scale-up mental health care.

Risk of Sex-Specific Cancers in Opposite-Sex and Same-Sex Twins in Denmark and Sweden.

BACKGROUND: Increasing evidence shows that some cancers originate in utero. It is hypothesized that elevated exposure to some steroid hormones might increase cancer risk and that hormone transfer between twin fetuses could result in different prenatal exposure to testosterone. METHODS: This large-scale prospective twin study compared opposite-sex (OS) and same-sex (SS) twins to test the impact of intrauterine exposures on cancer risk. On the basis of the Danish and Swedish twin and cancer registries, we calculated incidence rate ratios for OS and SS twins, whereas standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated for OS/SS twins compared with the general population. RESULTS: A total of 18,001 cancers were identified during 1943-2009. No significant differences were observed between OS and SS twins, neither for the sex-specific cancers nor for cancer at all sites. All-cause cancer was slightly reduced for OS and SS twins compared with the general population, significant for OS males (SIR, 0.95; 95% CI, 0.92-0.98) and for SS males and females (SIR, 0.97; 95% CI, 0.94-0.99). CONCLUSIONS: Our data suggest that having a male co-twin-which may entail higher exposure to prenatal testosterone-does not increase the risk of sex-specific cancers in OS females. Furthermore, the study supports that twinning per se is not a risk factor of cancer. IMPACT: Findings are reassuring, as they fail to provide evidence for the hypothesis that endocrine or other difference in the in utero milieu affects the risk of sex-specific cancers.

DCAF4, a novel gene associated with leucocyte telomere length.

BACKGROUND: Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR). RESULTS: Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10(-10)) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10(-3) and 2×10(-3), respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (p<0.05, <0.01, <0.005, <0.001) in the LTL-GWA meta-analysis, these genes were jointly over-represented for melanoma at p values ranging from 1.97×10(-169) to 3.42×10(-24). CONCLUSIONS: We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population.

An exploratory study of the socio-cultural risk influences for cigarette smoking among Southern Nigerian youth.

BACKGROUND: The increase in smoking prevalence in developing countries including Nigeria has been mainly blamed on the aggressive marketing strategies of big tobacco companies. There is a paucity of research on other socio-cultural risk factors for smoking among the youth. The main objective of this study is to explore and describe socio-cultural risk factors influencing cigarette smoking among the youth in Southern Nigeria. METHODS: A total of 27 respondents (5 community leaders, 4 political analysts and 18 young cigarette smokers) were interviewed using a semi-structured interview guide. Interpretative Phenomenological Analysis (IPA) was used to analyse the data. RESULTS: Social-cultural practices fuelling early usage and exposure of children to cigarettes and the promotional activities of tobacco companies were identified as possible factors influencing youth's smoking behaviour in Southern Nigeria. CONCLUSION: Tobacco control policies should include cultural interventions to modify current traditional practices and social norms which fuel the use of tobacco in the society. Such interventions must target specific groups, subpopulations and subcultures more exposed to the cultural risk influences for smoking.

Substance use and risky sexual behaviours among street connected children and youth in Accra, Ghana.

BACKGROUND: Research on street children and youth has shown that this population is at high risk for substance use. Though risky sexual behaviours have been investigated and widely reported among street youth in resource constrained-settings, few studies have explored the relationship between substance use and other risk behaviours. This study was therefore conducted to examine the association between substance use and risky sexual behaviours among homeless youth in Ghana. METHOD: A cross-sectional survey of a convenient sample of 227 (122 male and 105 female) street connected children and youth was conducted in Ghana in 2012. Using self-report measures, the relationship between substance use and risky sexual behaviours was examined using logistic regression. RESULTS: Substance use was relatively high as 12% and 16.2% reported daily use of alcohol and marijuana respectively. There were age and sex differences in substance use among the sample. As compared to males, more females had smoked cigarettes, used alcohol and marijuana. While alcohol use decrease with age, marijuana use on the other hand increases with age. Results from multivariate analysis revealed that having ever drunk alcohol and alcohol use in the past one month were independently associated with all the four indices of risky sexual behaviour (ever had sex, non-condom use, multiple sexual partners and survival sex). Both marijuana use and smoking of cigarettes were associated with having ever had sex, multiple sexual partners and survival sex. Other drug use was independently associated with non-condom use. CONCLUSION: Substance use seems to serve as a possible risk factor for sexual risk behaviours among homeless youth. Harm reduction interventions are needed to prevent street children and youth from engaging in substance use and risky sexual behaviours. Such programmes should pay special attention to females and younger children who are highly susceptible to the adverse conditions on the street.

Regulation of the pituitary-thyroid axis in adulthood is not related to birth weight: evidence from extremely birth weight-discordant monozygotic Danish twin pairs.

BACKGROUND: Low birth weight has been linked with changes in thyroid function in adulthood, but it is unknown whether fetal programming or underlying genetic and environmental factors explains the association. We hypothesized that birth weight influences the pituitary-thyroid set point in adults. METHODS: A total of 152 birth weight-discordant monozygotic twin pairs with a median age of 57 years (interquartile range: 33-63) were ascertained from the Danish Twin Registry in 2010. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and triiodothyronine (T3) levels were measured. Birth weights were retrieved from midwife records (individuals born before 1973) and the Danish Birth Record Registry (all other participants) RESULTS: Birth weight was inversely associated with serum levels of FT4 (ß=-0.48 pmol/[L·kg], p=0.014) and serum T3 (ß=-0.09 nmol/[L·kg], p=0.010), but not serum TSH after adjustment for age, sex, and current use of tobacco products, when the twins were investigated as singletons. Serum levels of TSH and T3 were similar in within twin-pair analyses, while serum FT4 was higher in twins with the lowest birth weight (median difference 0.3 mIU/L). When the analyses were repeated in twin pairs (n=46 pairs) characterized by extreme difference in birth weight (>0.5 kg), serum TSH, T3, and FT4 levels were similar in twins with high and low birth weight. The proportion of individuals with serum TSH level >4 mIU/L or <0.3 mIU/L was identical in both groups. CONCLUSIONS: No overall evidence of an association between birth weight and adult pituitary-thyroid axis set point, after control for genetic and environmental factors, could be demonstrated.

Age and gender effects on DNA strand break repair in peripheral blood mononuclear cells.

Exogenous and endogenous damage to DNA is constantly challenging the stability of our genome. This DNA damage increase the frequency of errors in DNA replication, thus causing point mutations or chromosomal rearrangements and has been implicated in aging, cancer, and neurodegenerative diseases. Therefore, efficient DNA repair is vital for the maintenance of genome stability. The general notion has been that DNA repair capacity decreases with age although there are conflicting results. Here, we focused on potential age-associated changes in DNA damage response and the capacities of repairing DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) in human peripheral blood mononuclear cells (PBMCs). Of these lesions, DSBs are the least frequent but the most dangerous for cells. We have measured the level of endogenous SSBs, SSB repair capacity, γ-H2AX response, and DSB repair capacity in a study population consisting of 216 individuals from a population-based sample of twins aged 40-77 years. Age in this range did not seem to have any effect on the SSB parameters. However, γ-H2AX response and DSB repair capacity decreased with increasing age, although the associations did not reach statistical significance after adjustment for batch effect across multiple experiments. No gender differences were observed for any of the parameters analyzed. Our findings suggest that in PBMCs, the repair of SSBs is maintained until old age, whereas the response to and the repair of DSBs decrease.

Genetic and environmental influences on odor identification ability in the very old.

Odor identification ability and cognition were measured in a population-based cohort of 1,222 very old twins and singletons, including 91 centenarians. Heritability for identifying odors was low, in contrast to that for cognition. Common genes were found to contribute to both olfaction and cognition. In a multiple regression model, sex, age, cognitive function, and smoking, but not APOEε4 status, were significant predictors of the olfactory test scores (all ps < 0.001). This study, along with data from other studies, suggests that indices of heritability for odor identification decline with age, likely reflecting adverse environmental influences on the smell system.

[Interdisciplinary geriatric intervention among nursing home residents with hip fracture reduces mortality]. / Tvaerfaglig geriatrisk postoperativ intervention hos aeldre i plejebolig med hoftenaer fraktur reducerer mortalitet.

INTRODUCTION: Nursing home residents represent the majority of hip fracture hospitalisation cases. Quick discharge to nursing homes after surgery is common practice. A previous study indicates an increased risk of death immediately after discharge. MATERIAL AND METHODS: A total of 211 residents, hospitalised from nursing homes for hip fracture surgery, were selected for a retrospective follow-up study. The orthopaedic ward's geriatric team (GO-team) visited the residents no later than one day after discharge. The number of visits depended on the need for treatment and rehabilitation. Intervention was, among others, focussed on: nutrition, fluid therapy and blood transfusion. RESULTS: Intensive geriatric intervention reduced the 30-day mortality (odds ratio (OR) = 0.08; 95% confidence interval (CI): 0.01; 0.52) and reduced 3-month mortality (OR = 0.03; 95% CI: 0.003; 0.25). Fluid therapy and nutritional support were associated with reduced probability of death (OR = 0.12; 95% CI: 0.02; 0.67)/(OR = 0.23; 95% CI: 0.07; 0.79). Non-elective readmissions were reduced (OR = 0.20; 95% CI: 0.04; 0.91). Post-surgical blood transfusion was associated with improved functional ability (beta = 8.22; 95% CI: 1.44; 15.0). CONCLUSION: Geriatric interdisciplinary intervention among residents in nursing homes has a positive effect and improves survival and reduces non-elective readmission within three months. Still, there is uncertainty about the effect of fluid therapy and blood transfusions and further investigations are needed.

'Mental health is everybody's business': roles for an intersectoral approach in South Africa.

Intersectoral action is increasingly recognized as necessary to address the social determinants of mental health. This study aims to assess South Africa's progress in intersectoral collaboration for mental health, and provide recommendations for intersectoral collaboration, to generate lessons for other low- and middle-income countries. We conducted a survey of the existing mental health system in South Africa using the World Health Organization Assessment Instrument for Mental Health Systems. We also conducted 96 semi-structured interviews and 12 focus group discussions with a range of stakeholders at national, provincial and district level. Data were analysed thematically to understand the roles and responsibilities of different sectors in realizing the right to mental health. A range of key sectors were identified as having roles in mental health promotion, illness prevention and service delivery. In discussing South Africa's progress, respondents gave several suggestions about how to formulate an intersectoral response in this context, including increasing high level political commitment, and using leadership from the health sector. We outline roles and responsibilities for various sectors and lessons that can be learnt from this context. These include the importance of developing programmes alongside legislation, employing targeted awareness-raising to engage sectors, and developing a structured approach to intersectoral action.

Genetic and environmental influences on plasma homocysteine: results from a Danish twin study.

BACKGROUND: Increased plasma homocysteine has been linked to many clinical conditions including atherosclerosis and ischemic stroke. We assessed the genetic and environmental influences on homocysteine in adult twins and tested the influence of 3 candidate polymorphisms. METHODS: Homocysteine was analyzed in 1206 healthy twins, who were genotyped for 3 polymorphisms: MTHFR 677C>T, MTR 2756A>G, and NNMT (dbSNP: rs694539). To perform quantitative trait linkage analysis of the MTHFR locus, the genotyping was supplemented with 2 genetic markers localized on each site of the MTHFR locus. The twin data were analyzed using biometric structural equation models as well as a combined association and linkage analysis in 2 age cohorts. RESULTS: Age, sex, and MTHFR genotype have a significant impact on homocysteine concentrations, whereas the other genotypes were not associated with homocysteine concentrations. The variance in homocysteine could be solely ascribed to additive genetic and nonshared environmental factors, with an estimated additive genetic proportion of total variation at age 18-39 years of 0.63 (95% CI, 0.53-0.71) and at age 40-65 years of 0.27 (95% CI, 0.10-0.41). The impact of the MTHFR locus is estimated to explain 53% (95% CI, 0.07-0.67) of the total phenotypic variation in persons 18-39 years old and 24% (95% CI, 0.00-0.39) in persons 40-65 years old, i.e., almost all additive genetic variance. CONCLUSIONS: Homocysteine concentrations have a high heritability that decreases with age. The MTHFR gene locus is responsible for almost all the variation attributable to genetic factors, leaving very little influence of other genetic variations.

Influence of environmental factors on facial ageing.

BACKGROUND: A recent twin study has shown that 'looking old for one's age' is associated with increased mortality. Approximately 40% of the variation in perceived age is due to non-genetic factors. OBJECTIVE: To examine environmental factors influencing perceived age controlling for diseases. DESIGN: A twin study. SETTING: In the 2001 wave of the population-based survey--the Longitudinal Study of Aging Danish Twins--participants provided information on a wide range of exposures and health indicators. Additionally, they were asked to have a face photograph taken. SUBJECTS: A total of 1826 elderly (70+) twins who had a high-quality face photograph taken. METHODS: Ten nurses assessed the visual age of each twin from the face photograph. The mean of the nurses' age estimates for each twin was used as the twin's perceived age. Multivariate linear regression and intrapair comparison (for intact twin pairs) were used for analyses. RESULTS: Statistically significant determinants of facial ageing associated with high perceived age for men were smoking (P = 0.01), sun exposure (P = 0.02) and low body mass index (BMI) (P<0.005), while for women they were low BMI (P = 0.05) and low social class (P<0.005). The number of children (men) and marital status (P = 0.08) and depression symptomatology score (women) were borderline significantly associated with facial ageing. CONCLUSION: Our study confirms previous findings of a negative influence of sun exposure, smoking and a low BMI on facial ageing. Furthermore, our study indicates that high social status, low depression score and being married are associated with a younger look, but the strength of the associations varies between genders.