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Background: Pre-exposure prophylaxis (PrEP) is an emerging biomedical prevention intervention. Documenting PrEP service delivery models (SDMs) that promote linkage to and continuation of PrEP will inform guidelines and maximise roll-out., Objectives: To synthesise and appraise the effectiveness and feasibility of PrEP SDMs designed to promote linkage to PrEP care among adolescent girls and young women (AGYW) and men in sub-Saharan Africa (SSA)., Eligibility Criteria: Primary quantitative and qualitative studies published in English and conducted in SSA were included. No restrictions on the date of publication were applied., Sources of Evidence: Methodology outlined in the Joanna Briggs Institute reviewers' manual was followed. PubMed, Cochrane library, Scopus, Web of Science and online-conference abstract archives were searched., Charting Methods: Data on article, population, intervention characteristics and key outcomes was charted in REDCap., Results and Conclusion: Of the 1204 identified records, 37 (met the inclusion criteria. Health facility-based integrated models of PrEP delivery with family planning, maternal and child health or sexual and reproductive services to AGYW resulted in PrEP initiation of 16%-90%. Community-based drop-in centres (66%) was the preferred PrEP outlet for AGYW compared with public clinics (25%) and private clinics (9%). Most men preferred community-based delivery models. Among individuals who initiated PrEP, 50% were men, 62% were <35 years old and 97% were tested at health fairs compared with home testing. Integrated antiretroviral therapy (ART)-PrEP delivery was favoured among serodiscordant couples with 82.9% of couples using PrEP or ART with no HIV seroconversions. PrEP initiation within healthcare facilities was increased by perceived client-friendly services and non-judgemental healthcare workers. Barriers to PrEP initiation included distance to travel to and time spent at health facilities and perceived community stigma. PrEP SDMs for AGYW and men need to be tailored to the needs and preferences for each group. Programme implementers should promote community-based SDMs to increase PrEP initiation among AGYW and men., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Globally, a growing body of research has shown that ambient air pollution is one of the most critical environmental issues, especially in relation to human health. Exposure to ambient air pollution leads to serious health conditions such as lower respiratory infections, cancers, diabetes mellitus type 2, ischaemic heart disease, stroke and chronic obstructive pulmonary disease., Objectives: To estimate the burden of disease attributable to ambient air pollution in South Africa (SA) for the years 2000, 2006 and 2012., Methods: Comparative risk assessment method was used to determine the burden of disease due to two pollutants (particulate matter (PM2.5) and ambient ozone). Regionally optimised fully coupled climate chemistry models and surface air pollution observations were used to generate concentrations of PM2.5 and ozone for each SA Census Small Area Level, for the year 2012. For 2000 and 2006, population-weighted PM2.5and ozone were estimated, based on the 2012 results. Following the identification of disease outcomes associated with particulate matter with aerodynamic diameter <2.5 μm (PM2.5) and ozone exposure, the attributable burden of disease was estimated for 2000, 2006 and 2012. Furthermore, for the year 2012, the burden of disease attributable to ambient air pollution exposure was computed at provincial levels., Results: In 2012, approximately 97.6% of people in SA were exposed to PM2.5 at levels above the 2005 World Health Organization guideline: 10 μg/m3 annual mean. From 2000 to 2012, population-weighted annual average PM2.5 increased from 26.6 μg/m3 to 29.7 μg/m3, and ozone 6-month high 8-hour daily maximum increased from 64.4 parts per billion (ppb) to 72.1 ppb. At a national scale, in the year 2000, 15 619 (95% uncertainty interval (UI) 8 958 - 21 849) deaths were attributed to PM2.5 exposure, while 1 326 (95% UI 534 - 1 885) deaths were attributed to ozone. In 2006, an estimated 19 672 deaths (95% UI 11 526 - 27 086) were attributed to PM2.5, and a further 1 591 deaths (95% UI 651 - 2 236) to ozone exposure. In 2012, deaths attributed to PM2.5 were 19 507 (95% UI 11 318 - 27 111), and to ozone 1 734 (95% UI 727 - 2 399). Additionally, population-weighted provincial scale analysis showed that Gauteng Province had the highest number of attributable deaths due to both PM2.5 and ozone in 2012., Conclusion: The study showed that ambient air pollution exposure is an important health risk in SA, requiring both short- and long-term intervention. In the short term, the SA Ambient Air Quality Standards and industrial minimum emissions standards need to be enforced. In the longer term, to reduce air pollution and the associated disease burden, the combustion of fossil fuels as a source of energy for power generation and transportation, as well as industrial and domestic uses, needs to be replaced with clean renewable energy sources. In addition to local measures, when the southern African prevalent anticyclonic air dynamics that transport regionally emitted pollutants into SA (especially from biomass burning) are considered, it is also advisable to establish long-term regional co-operation in reducing air pollution.

Background: Ongoing quantification of the disease burden attributable to smoking is important to monitor and strengthen tobacco control policies., Objectives: To estimate the attributable burden due to smoking in South Africa for 2000, 2006 and 2012., Methods: We estimated attributable burden due to smoking for selected causes of death in South African (SA) adults aged ≥35 years for 2000, 2006 and 2012. We combined smoking prevalence results from 15 national surveys (1998 - 2017) and smoking impact ratios using national mortality rates. Relative risks between smoking and select causes of death were derived from local and international data., Results: Smoking prevalence declined from 25.0% in 1998 (40.5% in males, 10.9% in females) to 19.4% in 2012 (31.9% in males, 7.9% in females), but plateaued after 2010. In 2012 tobacco smoking caused an estimated 31 078 deaths (23 444 in males and 7 634 in females), accounting for 6.9% of total deaths of all ages (17.3% of deaths in adults aged ≥35 years), a 10.5% decline overall since 2000 (7% in males; 18% in females). Age-standardised mortality rates (and disability-adjusted life years (DALYs)) similarly declined in all population groups but remained high in the coloured population. Chronic obstructive pulmonary disease accounted for most tobacco-attributed deaths (6 373), followed by lung cancer (4 923), ischaemic heart disease (4 216), tuberculosis (2 326) and lower respiratory infections (1 950). The distribution of major causes of smoking-attributable deaths shows a middle- to high-income pattern in whites and Asians, and a middle- to low-income pattern in coloureds and black Africans. The role of infectious lung disease (TB and LRIs) has been underappreciated. These diseases comprised 21.0% of deaths among black Africans compared with only 4.3% among whites. It is concerning that smoking rates have plateaued since 2010., Conclusion: The gains achieved in reducing smoking prevalence in SA have been eroded since 2010. An increase in excise taxes is the most effective measure for reducing smoking prevalence. The advent of serious respiratory pandemics such as COVID-19 has increased the urgency of considering the role that smoking cessation/abstinence can play in the prevention of, and post-hospital recovery from, any condition.

Background: South Africa (SA) faces multiple health challenges. Quantifying the contribution of modifiable risk factors can be used to identify and prioritise areas of concern for population health and opportunities for health promotion and disease prevention interventions., Objective: To estimate the attributable burden of 18 modifiable risk factors for 2000, 2006 and 2012., Methods: Comparative risk assessment (CRA), a standardised and systematic approach, was used to estimate the attributable burden of 18 risk factors. Risk exposure estimates were sourced from local data, and meta-regressions were used to model the parameters, depending on the availability of data. Risk-outcome pairs meeting the criteria for convincing or probable evidence were assessed using relative risks against a theoretical minimum risk exposure level to calculate either a potential impact fraction or population attributable fraction (PAF). Relative risks were sourced from the Global Burden of Disease, Injuries, and Risk Factors (GBD) study as well as published cohort and intervention studies. Attributable burden was calculated for each risk factor for 2000, 2006 and 2012 by applying the PAF to estimates of deaths and years of life lost from the Second South African National Burden of Disease Study (SANBD2). Uncertainty analyses were performed using Monte Carlo simulation, and age-standardised rates were calculated using the World Health Organization standard population., Results: Unsafe sex was the leading risk factor across all years, accounting for one in four DALYs (26.6%) of the estimated 20.6 million DALYs in 2012. The top five leading risk factors for males and females remained the same between 2000 and 2012. For males, the leading risks were (in order of descending rank): unsafe sex; alcohol consumption; interpersonal violence; tobacco smoking; and high systolic blood pressure; while for females the leading risks were unsafe sex; interpersonal violence; high systolic blood pressure; high body mass index; and high fasting plasma glucose. Since 2000, the attributable age-standardised death rates decreased for most risk factors. The largest decrease was for household air pollution (-41.8%). However, there was a notable increase in the age-standardised death rate for high fasting plasma glucose (44.1%), followed by ambient air pollution (7%)., Conclusion: This study reflects the continued dominance of unsafe sex and interpersonal violence during the study period, as well as the combined effects of poverty and underdevelopment with the emergence of cardiometabolic-related risk factors and ambient air pollution as key modifiable risk factors in SA. Despite reductions in the attributable burden of many risk factors, the study reveals significant scope for health promotion and disease prevention initiatives and provides an important tool for policy makers to influence policy and programme interventions in the country.

Background: A high body mass index (BMI) is associated with several cardiovascular diseases, diabetes and chronic kidney disease, cancers, and other selected health conditions., Objectives: To quantify the deaths and disability-adjusted life years (DALYs) attributed to high BMI in persons aged ≥20 years in South Africa (SA) for 2000, 2006 and 2012., Methods: The comparative risk assessment (CRA) methodology was followed. Meta-regressions of the BMI mean and standard deviation from nine national surveys spanning 1998 - 2017 were conducted to provide estimates by age and sex for adults aged ≥20 years. Population attributable fractions were calculated for selected health outcomes using relative risks identified by the Global Burden of Disease Study (2017), and applied to deaths and DALY estimates from the second South African National Burden of Disease Study to estimate the burden attributed to high BMI in a customised Microsoft Excel workbook. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. BMI was assumed to follow a log-normal distribution, and the theoretical minimum value of BMI below which no risk was estimated was assumed to follow a uniform distribution from 20 kg/m2 to 25 kg/m2., Results: Between 2000 and 2012, mean BMI increased by 6% from 27.7 kg/m2 (95% confidence interval (CI) 27.6 - 27.9) to 29.4 kg/m2 (95% CI 29.3 - 29.5) for females, and by 3% from 23.9 kg/m2 (95% CI 23.7 - 24.1) to 24.6 kg/m2 (95% CI 24.5 - 24.8) for males. In 2012, high BMI caused 58 757 deaths (95% uncertainty interval (UI) 46 740 - 67 590) or 11.1% (95% UI 8.8 - 12.8) of all deaths, and 1.42 million DALYs (95% UI 1.15 - 1.61) or 6.9% (95% UI 5.6 - 7.8) of all DALYs. Over the study period, the burden in females was ~1.5 - 1.8 times higher than that in males. Type 2 diabetes mellitus became the leading cause of death attributable to high BMI in 2012 (n=12 382 deaths), followed by hypertensive heart disease (n=12 146), haemorrhagic stroke (n=9 141), ischaemic heart disease (n=7 499) and ischaemic stroke (n=4 044). The age-standardised attributable DALY rate per 100 000 population for males increased by 6.6% from 3 777 (95% UI 2 639 - 4 869) in 2000 to 4 026 (95% UI 2 831 - 5 115) in 2012, while it increased by 7.8% for females from 6 042 (95% UI 5 064 - 6 702) to 6 513 (95% UI 5 597 - 7 033)., Conclusion: Average BMI increased between 2000 and 2012 and accounted for a growing proportion of total deaths and DALYs. There is a need to develop, implement and evaluate comprehensive interventions to achieve lasting change in the determinants and impact of overweight and obesity, particularly among women.

Background: Household air pollution (HAP) due to the use of solid fuels for cooking is a global problem with significant impacts on human health, especially in low- and middle-income countries. HAP remains problematic in South Africa (SA). While electrification rates have improved over the past two decades, many people still use solid fuels for cooking owing to energy poverty., Objectives: To estimate the disease burden attributable to HAP for cooking in SA over three time points: 2000, 2006 and 2012., Methods: Comparative risk assessment methodology was used. The proportion of South Africans exposed to HAP was assessed and assigned the estimated concentration of particulate matter with a diameter <2.5 μg/m3 (PM2.5) associated with HAP exposure. Health outcomes and relative risks associated with HAP exposure were identified. Population-attributable fractions and the attributable burden of disease due to HAP exposure (deaths, years of life lost, years lived with disability and disability-adjusted life years (DALYs)) for SA were calculated. Attributable burden was estimated for 2000, 2006 and 2012. For the year 2012, we estimated the attributable burden at provincial level., Results: An estimated 17.6% of the SA population was exposed to HAP in 2012. In 2012, HAP exposure was estimated to have caused 8 862 deaths (95% uncertainty interval (UI) 8 413 - 9 251) and 1.7% (95% UI 1.6% - 1.8%) of all deaths in SA, respectively. Loss of healthy life years comprised 208 816 DALYs (95% UI 195 648 - 221 007) and 1.0% of all DALYs (95% UI 0.95% - 1.0%) in 2012, respectively. Lower respiratory infections and cardiovascular disease contributed to the largest proportion of deaths and DALYs. HAP exposure due to cooking varied across provinces, and was highest in Limpopo (50.0%), Mpumalanga (27.4%) and KwaZulu-Natal (26.4%) provinces in 2012. Age standardised burden measures showed that these three provinces had the highest rates of death and DALY burden attributable to HAP., Conclusion: The burden of disease from HAP due to cooking in SA is of significant concern. Effective interventions supported by legislation and policy, together with awareness campaigns, are needed to ensure access to clean household fuels and improved cook stoves. Continued and enhanced efforts in this regard are required to ensure the burden of disease from HAP is curbed in SA.

Background: National estimates of childhood undernutrition display uncertainty; however, it is known that stunting is the most prevalent deficiency. Child undernutrition is manifest in poor communities but is a modifiable risk factor. The intention of the study was to quantify trends in the indicators of child undernutrition to aid policymakers., Objectives: To estimate the burden of diseases attributable to stunting, wasting and underweight and their aggregate effects in South African (SA) children under the age of 5 years during 2000, 2006 and 2012., Methods: The study applied comparative risk assessment methodology. Data sources for estimates of prevalence and population distribution of exposure in children under 5 years were the National Food Consumption surveys and the SA National Health and Nutrition Examination Survey conducted close to the target year of burden. Childhood undernutrition was estimated for stunting, wasting and underweight and their combined 'aggregate effect' using the World Health Organization (WHO) 2006 standard. Population-attributable fractions for the disease outcomes of diarrhoea, lower respiratory tract infections, measles and protein-energy malnutrition were applied to SA burden of disease estimates of deaths, years of life lost, years lived with a disability and disability-adjusted life years for 2000, 2006 and 2012., Results: Among children aged under 5 years between 1999 and 2012, the distribution of anthropometric measurements <‒2 standard deviations from the WHO median showed little change for stunting (28.4% v. 26.6%), wasting (2.6% v. 2.8%) and underweight (7.6% v. 6.1%). In the same age group in 2012, attributable deaths due to wasting and aggregated burden accounted for 21.4% and 33.2% of the total deaths, respectively. Attributable death rates due to wasting and aggregate effects decreased from ~310 per 100 000 in 2006 to 185 per 100 000 in 2012., Conclusion: The study shows that reduction of childhood undernutrition would have a substantial impact on child mortality. We need to understand why we are not penetrating the factors related to nutrition of children that will lead to reducing levels of stunting.

Background: Low intake of fruit and vegetables is associated with an increased risk of various non-communicable diseases, including major causes of death and disability such as cardiovascular disease, diabetes mellitus and cancers. Diets low in fruit and vegetables are prevalent in the South African (SA) population, and average intake is well below the internationally recommended threshold., Objectives: To estimate the burden of disease attributable to a diet low in fruit and vegetables by sex and age group in SA for the years 2000, 2006 and 2012., Methods: We followed World Health Organization and Global Burden of Disease Study comparative risk assessment methodology. Population attributable fractions - calculated from fruit and vegetable intake estimated from national and local surveys and relative risks for health outcomes based on the current literature - were applied to the burden estimates from the second South African National Burden of Disease Study (SANBD2). Outcome measures included deaths and disability-adjusted life years (DALYs) lost from ischaemic heart disease, stroke, type 2 diabetes, and five categories of cancers., Results: Between 2000 and 2012, the average intake of fruit of the SA adult population (≥25 years) declined by 7%, from 48.5 g/d (95% uncertainty interval (UI) 46.6 - 50.5) to 45.2 g/d (95% UI 42.7 - 47.6). Vegetable intake declined by 25%, from 146.9 g/d (95% UI 142.3 - 151.8) to 110.5 g/d (95% UI 105.9 - 115.0). In 2012, these consumption patterns are estimated to have caused 26 423 deaths (95% UI 24 368 - 28 006), amounting to 5.0% (95% UI 4.6 - 5.3%) of all deaths in SA, and the loss of 514 823 (95% UI 473 508 - 544 803) healthy life years or 2.5% (95% UI 2.3 - 2.6%) of all DALYs. Cardiovascular disease comprised the largest proportion of the attributable burden, with 83% of deaths and 84% of DALYs. Age-standardised death rates were higher for males (145.1 deaths per 100 000; 95% UI 127.9 - 156.2) than for females (108.0 deaths per 100 000; 95% UI 96.2 - 118.1); in both sexes, rates were lower than those observed in 2000 (-9% and -12%, respectively)., Conclusion: Despite the overall reduction in standardised death rates observed since 2000, the absolute burden of disease attributable to inadequate intake of fruit and vegetables in SA remains of significant concern. Effective interventions supported by legislation and policy are needed to reverse the declining trends in consumption observed in most age categories and to curb the associated burden.

Background: Worldwide, higher-than-optimal fasting plasma glucose (FPG) is among the leading modifiable risk factors associated with all- cause mortality and disability-adjusted life years (DALYs) due to the direct sequelae of diabetes and the increased risk for cardiovascular and chronic kidney disease., Objectives: To report deaths and DALYs of health outcomes attributable to high FPG by age and sex for South Africa (SA) for 2000, 2006 and 2012., Methods: Comparative risk assessment methodology was used to estimate the burden attributable to high FPG. A meta-regression analysis was performed using data from national and small-area studies to estimate the population distribution of FPG and diabetes prevalence. Attributable fractions were calculated for selected health outcomes and applied to local burden estimates from the second South African National Burden of Disease Study (SANBD2). Age-standardised rates were calculated using World Health Organization world standard population weights., Results: We estimated a 5% increase in mean FPG from 5.31 (95% confidence interval (CI) 5.18 - 5.43) mmol/L to 5.57 (95% CI 5.41 - 5.72) mmol/L and a 75% increase in diabetes prevalence from 7.3% (95% CI 6.7 - 8.3) to 12.8% (95% CI 11.9 - 14.0) between 2000 and 2012. The age-standardised attributable death rate increased from 153.7 (95% CI 126.9 - 192.7) per 100 000 population in 2000 to 203.5 (95% CI 172.2 - 240.8) per 100 000 population in 2012, i.e. a 32.4% increase. During the same period, age-standardised attributable DALY rates increased by 43.8%, from 3 000 (95% CI 2 564 - 3 602) per 100 000 population in 2000 to 4 312 (95% CI 3 798 - 4 916) per 100 000 population in 2012. In each year, females had similar attributable death rates to males but higher DALY rates. A notable exception was tuberculosis, with an age-standardised attributable death rate in males double that in females in 2000 (14.3 v. 7.0 per 100 000 population) and 2.2 times higher in 2012 (18.4 v. 8.5 per 100 000 population). Similarly, attributable DALY rates were higher in males, 1.7 times higher in 2000 (323 v. 186 per 100 000 population) and 1.6 times higher in 2012 (502 v. 321 per 100 000 population). Between 2000 and 2012, the age-standardised death rate for chronic kidney disease increased by 98.3% (from 11.7 to 23.1 per 100 000 population) and the DALY rate increased by 116.9% (from 266 to 578 per 100 000 population)., Conclusion: High FPG is emerging as a public health crisis, with an attributable burden doubling between 2000 and 2012. The consequences are costly in terms of quality of life, ability to earn an income, and the economic and emotional burden on individuals and their families. Urgent action is needed to curb the increase and reduce the burden associated with this risk factor. National data on FPG distribution are scant, and efforts are warranted to ensure adequate monitoring of the effectiveness of the interventions.

Background: The incidence of diarrhoeal disease is closely linked to socioeconomic and environmental factors, household practices and access to health services. South African (SA) district health information and national survey data report wide variation in the incidence and prevalence of diarrhoeal episodes in children under 5 years of age. These differentials indicate potential for reducing the disease burden through improvements in provision of water and sanitation services and changes in hygiene behaviour., Objectives: To estimate the burden of disease attributed to unsafe water, sanitation and hygiene (WASH) by province, sex and age group for SA in 2000, 2006 and 2012., Methods: Comparative risk assessment methodology was used to estimate the disease burden attributable to an exposure by comparing the observed risk factor distribution with a theoretical lowest possible population distribution. The study adapts the original World Health Organization scenario-based approach for estimating diarrhoeal disease burden from unsafe WASH, by assigning different standards of household water and sanitation-specific geographical classification to capture SA living conditions in rural, urban and informal settlements., Results: SA experienced an improvement in water and sanitation supply in eight of the nine provinces between 2001 and 2011, with the exception of Northern Cape Province. In 2011, 41% of South Africans lived with poor water and sanitation conditions; however, wide provincial inequalities exist. In 2012, it was estimated that 84.1% of all deaths due to diarrhoeal disease were attributable to unsafe WASH; this equates to 13 757 deaths (95% uncertainty interval (UI) 13 015 - 14 300). Of these diarrhoeal disease deaths, 48.2% occurred in children under 5 years of age, accounting for 13.9% of all deaths in this age group (95% UI 13.1 - 14.4). Between 2000 and 2012, the proportion of deaths attributable to diarrhoea reduced from 3.6% to 2.6%. Gauteng and Western Cape provinces experienced much lower WASHattributable death rates than the more rural, poorer provinces., Conclusion: Unsafe WASH remains an important risk factor for disease in SA, especially in children. High priority needs to be given to the provision of safe and sustainable sanitation and water facilities and promoting safe hygiene behaviours. The COVID-19 pandemic has reinforced the critical importance of clean water for preventing and containing disease.

Background: Worldwide, iron deficiency, and consequent iron-deficiency anaemia, remains the most common nutritional disorder. Iron-deficiency anaemia mostly affects young children and women of reproductive age, especially in Asia and Africa. Iron deficiency may contribute to disability directly or indirectly as a risk factor for other causes of death, and may rarely contribute to death., Objectives: To estimate the changing burden of disease attributable to iron deficiency in males and females (all ages) for the years 2000, 2006 and 2012 in South Africa (SA)., Methods: The comparative risk assessment methodology developed by the World Health Organization (WHO) and the Global Burden of Diseases, Injuries, and Risk Factors Studies was used to estimate the burden attributable to iron deficiency in SA for the years 2000, 2006 and 2012. We attributed 100% of the estimated iron-deficiency anaemia burden across all age groups by sex to iron deficiency. For maternal conditions, the attributable burden to iron deficiency was calculated using the counterfactual method and applied to all women of reproductive age. The population attributable fraction calculated for these selected health outcomes was then applied to local burden estimates from the Second SA National Burden of Disease Study (SANBD2). Age-standardised rates were calculated using WHO world standard population weights and SA mid-year population estimates., Results: There was a slight decrease in the prevalence of iron-deficiency anaemia in women of reproductive age from ~11.9% in 2000 to 10.0% in 2012, although the prevalence of anaemia fluctuated over time (25.5% - 33.2%), with a peak in 2006. There has been a gradual decline in the number of deaths from maternal conditions attributable to iron deficiency in SA between 2000 (351 deaths (95% uncertainty interval (UI) 248 - 436)) and 2012 (307 deaths (95% UI 118 - 470)), with a peak in 2006 (452 deaths (95% UI 301 - 589)). Furthermore, our analysis showed a 26% decrease between 2000 and 2012 in the age-standardised burden rates from maternal conditions (truncated to 15 - 49 years) attributable to iron deficiency. Between 2000 and 2012, the age-standardised disability-adjusted life year (DALY) rate from iron-deficiency anaemia attributable to iron deficiency markedly decreased by 33% in males, and increased by 3% in females of all ages. Approximately 1.1 - 1.4% of all DALYs in SA from 2000 to 2012 were attributable to iron deficiency., Conclusion: Iron-deficiency anaemia prevalence can be markedly reduced if iron deficiency is eliminated. Hence it is essential to encourage, reappraise and strengthen the measures that have been put in place to address iron deficiency, especially in women of reproductive age and children.

Introduction: Tobacco smoking and alcohol consumption during pregnancy are particularly prevalent in low socioeconomic status populations, with an adverse association with birth outcomes and cardiometabolic risk factors. However, the direct and indirect effects of prenatal cigarette smoking and alcohol consumption during pregnancy on cardiometabolic risk in offspring have been rather inconsistent. This may be attributed to multiple factors, such as the amount and timing of exposure to tobacco smoking and alcohol during pregnancy; the influence of maternal, environmental and socioeconomic factors; or how risk factors were defined by individual researchers and studies. Therefore, this review aims to provide a summary of the most recent evidence on birth outcomes and cardiometabolic risk in children associated with alcohol and/or tobacco exposure in utero., Methods and Analysis: PubMed, Scopus and Web of Science will be searched to identify published articles from 1 January 2001. Clinical studies that investigate the association between maternal cigarette smoking or alcohol consumption and birth weight and cardiometabolic risk factors in infants, children and adolescents will be included. Prospective cohort, case-control studies and birth cohort studies will be eligible for inclusion. Grey literature will be searched including conference proceedings, Google Scholar and the ProQuest Dissertation and Theses database. Only studies published in English will be included, with no restrictions regarding country, race or gender. Two independent reviewers will conduct the literature search and article screening. Eligibility criteria will be based on the population (infants, children, adolescents), exposure (maternal cigarette smoking, alcohol consumption or both), comparator (control group with no exposure during pregnancy) and outcomes (birth weight and cardiometabolic risk factors). Quality assessment and risk of bias will be assessed using a risk of bias tool for observational studies, and data will be extracted for analysis using a researcher-generated data extraction form. A meta-analysis will be performed to estimate pooled effect sizes if there are sufficient good-quality studies available. Sources of heterogeneity will be explored using subgroup analysis., Ethics and Dissemination: Ethical clearance will not be required as this review will extract publicly available secondary data. Findings from this review will be disseminated via publication in a peer-review journal., Prospero Registration Number: CRD42021286630., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To review prevalence studies of multimorbidity in South Africa to identify prevalence estimates, common disease clusters and factors associated with multimorbidity., Design: Systematic review., Setting: South Africa (general community and healthcare facilities)., Data Sources: Articles were retrieved from electronic databases (PubMed, Web of Science, Scopus, CINAHL, Science Direct and JSTOR)., Eligibility Criteria: Studies addressing the prevalence of multimorbidity in South Africa were eligible for inclusion. A systematic search was done in various databases up to December 2020. A risk of bias assessment was conducted for each article using a modified checklist., Study Selection: Two researchers independently screened titles and abstracts; assessed the risk of bias of each study and extracted data. Included studies were described using a narrative synthesis., Results: In total, 1407 titles were retrieved; of which 10 articles were included in the narrative synthesis. Six studies had a low risk of bias and three had a moderate risk of bias. One study was not assessed for risk of bias, because there was no criteria that apply to routine health information systems. Three of the included studies were population-based surveys, four were community-based cohorts and three cross-sectional studies of health facility data. The prevalence of multimorbidity was low to moderate (3%-23%) in studies that included younger people or had a wide range of selected age groups; and moderate to high (30%-87%) in studies of older adults. The common disease clusters were hypertension and diabetes, hypertension and HIV, and TB and HIV., Conclusion: All studies indicated that multimorbidity is a norm in South Africa, especially among older adults. Hypertension is the main driver of multimorbidity. Research on multimorbidity in South Africa needs to be strengthened with high-quality study designs., Prospero Registration Number: CRD42020196895., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Multimorbidity has increased globally over the past two decades, due to ageing populations and increased burden of non-communicable diseases (NCDs). In a country like South Africa, with a growing burden of NCDs and a high prevalence of HIV, information on multimorbidity can improve planning for healthcare delivery and utilisation, and reduce costs in the context of constrained health resources. This review aims to synthesise prevalence studies on multimorbidity, and identify dominant clusters and trends of multimorbidity in South Africa., Methods and Analysis: We will search electronic bibliographic databases (PubMed, Scopus, JSTOR, POPLINE, PsycINFO, ScienceDirect, Web of Science and CINAHL), and the reference lists of included articles. Two researchers will independently screen title and abstracts, and then full text to identify studies published before and in 2020 that report on prevalence of multimorbidity in South Africa. Risk of bias assessments will be done for each study. Information on the prevalence of multimorbidity and disease clusters will be extracted from each study. Where possible, prevalence of specific clusters of multimorbidity will be pooled using a random effects meta-analysis to account for variability between studies. The I 2 statistic will be used to establish the extent of heterogeneity due to variation in prevalence estimates rather than due to chance. The systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses., Ethics and Dissemination: Only published journal articles will be included in the systematic review. This review received ethics approval as part of a larger project by the University of the Western Cape Biomedical Science Research Ethics Committee (BM20/5/8). The findings from this research will be used to estimate the prevalence of multimorbidity in South Africa and will contribute to the design of future research projects. The findings will be disseminated in a peer-reviewed journal article., Prospero Registration Number: CRD42020196895., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Postpartum constipation, with symptoms, such as pain or discomfort, straining, and hard stool, is a common condition affecting mothers. Haemorrhoids, pain at the episiotomy site, effects of pregnancy hormones, and haematinics used in pregnancy can increase the risk of postpartum constipation. Eating a high-fibre diet and increasing fluid intake are usually encouraged. Although laxatives are commonly used in relieving constipation, the effectiveness and safety of available interventions for preventing postpartum constipation should be ascertained. This is an update of a review first published in 2015., Objectives: To evaluate the effectiveness and safety of interventions for preventing postpartum constipation., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, and two trials registers ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 October 2019), and screened reference lists of retrieved trials., Selection Criteria: We considered all randomised controlled trials (RCTs) comparing any intervention for preventing postpartum constipation versus another intervention, placebo, or no intervention in postpartum women. Interventions could include pharmacological (e.g. laxatives) and non-pharmacological interventions (e.g. acupuncture, educational and behavioural interventions). Quasi-randomised trials and cluster-RCTs were eligible for inclusion; none were identified. Trials using a cross-over design were not eligible., Data Collection and Analysis: Two review authors independently screened the results of the search to select potentially relevant trials, extracted data, assessed risk of bias, and the certainty of the evidence, using the GRADE approach. We did not pool results in a meta-analysis, but reported them per study., Main Results: We included five trials (1208 postpartum mothers); three RCTs and two quasi-RCTs. Four trials compared a laxative with placebo; one compared a laxative plus a bulking agent versus the same laxative alone, in women who underwent surgical repair of third degree perineal tears. Trials were poorly reported, and four of the five trials were published over 40 years ago. We judged the risk of bias to be unclear for most domains. Overall, we found a high risk of selection and attrition bias. Laxative versus placebo We included four trials in this comparison. Two of the trials examined the effects of laxatives that are no longer used; one has been found to have carcinogenic properties (Danthron), and the other is not recommended for lactating women (Bisoxatin acetate); therefore, we did not include their results in our main findings. None of the trials included in this comparison assessed our primary outcomes: pain or straining on defecation, incidence of postpartum constipation, or quality of life; or many of our secondary outcomes. A laxative (senna) may increase the number of women having their first bowel movement within 24 hours after delivery (risk ratio (RR) 2.90, 95% confidence interval (CI) 2.24 to 3.75; 1 trial, 471 women; low-certainty evidence); may have little or no effect on the number of women having their first bowel movement on day one after delivery (RR 0.94, 95% CI 0.72 to 1.22; 1 trial, 471 women; very low-certainty evidence); may reduce the number of women having their first bowel movement on day two (RR 0.23, 95% CI 0.11 to 0.45; 1 trial, 471 women; low-certainty evidence); and day three (RR 0.05, 95% CI 0.00 to 0.89; 1 trial, 471 women; low-certainty evidence); and may have little or no effect on the number of women having their first bowel movement on day four after delivery (RR 0.22, 95% CI 0.03 to 1.87; 1 trial, 471 women; very low-certainty evidence), but some of the evidence is very uncertain. Adverse effects were poorly reported. Low-certainty evidence suggests that the laxative (senna) may increase the number of women experiencing abdominal cramps (RR 4.23, 95% CI 1.75 to 10.19; 1 trial, 471 women). Very low-certainty evidence suggests that laxatives taken by the mother may have little or no effect on loose stools in the baby (RR 0.62, 95% CI 0.16 to 2.41; 1 trial, 281 babies); or diarrhoea (RR 2.46, 95% CI 0.23 to 26.82; 1 trial, 281 babies). Laxative plus bulking agent versus laxative only Very low-certainty evidence from one trial (147 women) suggests no evidence of a difference between these two groups of women who underwent surgical repair of third degree perineal tears; only median and range data were reported. The trial also reported no evidence of a difference in the incidence of postpartum constipation (data not reported), but did not report on quality of life. Time to first bowel movement was reported as a median (range); very low-certainty evidence suggests little or no difference between the two groups. A laxative plus bulking agent may increase the number of women having any episode of faecal incontinence during the first 10 days postpartum (RR 1.81, 95% CI 1.01 to 3.23; 1 trial, 147 women; very low-certainty evidence). The trial did not report on adverse effects of the intervention on babies, or many of our secondary outcomes., Authors' Conclusions: There is insufficient evidence to make general conclusions about the effectiveness and safety of laxatives for preventing postpartum constipation. The evidence in this review was assessed as low to very low-certainty evidence, with downgrading decisions based on limitations in study design, indirectness and imprecision. We did not identify any trials assessing educational or behavioural interventions. We identified four trials that examined laxatives versus placebo, and one that examined laxatives versus laxatives plus stool bulking agents. Further, rigorous trials are needed to assess the effectiveness and safety of laxatives during the postpartum period for preventing constipation. Trials should assess educational and behavioural interventions, and positions that enhance defecation. They should report on the primary outcomes from this review: pain or straining on defecation, incidence of postpartum constipation, quality of life, time to first bowel movement after delivery, and adverse effects caused by the intervention, such as: nausea or vomiting, pain, and flatus., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

In this systematic review, we assessed the effectiveness of systemic antibiotics as an adjunctive therapy to mechanical debridement in improving inflammatory systemic biomarkers, as compared to mechanical debridement alone, among adults with chronic periodontitis. We searched relevant electronic databases for eligible randomized controlled trials. Two review authors independently screened, extracted data, and assessed risk of bias. We conducted meta-analysis, assessed heterogeneity, and assessed certainty of evidence using GRADEPro software. We included 19 studies (n = 1350 participants), representing 18 randomized controlled trials and found very little or no impact of antibiotics on inflammatory biomarkers. A meta-analysis of eight studies demonstrated a mean reduction of 0.26 mm in the periodontal pockets at three months (mean difference [MD] -0.26, 95%CI: -0.36 to -0.17, n = 372 participants, moderate certainty of evidence) in favor of the antibiotics. However, results from five studies reporting clinical attachment level (mm) yielded little or no difference at three months (MD -0.16, 95% CI: -0.35 to 0.03, n = 217 participants) between antibiotic and placebo groups. There is little or no evidence that adjunctive systemic antibiotics therapy improves inflammatory systemic biomarkers, compared to mechanical debridement alone, among adults with chronic periodontitis.

Background: Postpartum constipation, with symptoms such as pain or discomfort, straining, and hard stool, is a common condition affecting mothers. Haemorrhoids, pain at the episiotomy site, effects of pregnancy hormones and haematinics used in pregnancy can increase the risk of postpartum constipation. Eating a high-fibre diet and increasing fluid intake is usually encouraged, although laxatives are commonly used in relieving constipation. The effectiveness and safety of available interventions for preventing postpartum constipation needs to be ascertained., Objectives: To evaluate the effectiveness and safety of interventions for preventing postpartum constipation., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2015), Stellenbosch University database, ProQuest Dissertation and Theses database, World Health Organization International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov (30 April 2015) and reference lists of included studies., Selection Criteria: All randomised controlled trials (RCTs) comparing any intervention for preventing postpartum constipation versus another intervention, placebo or no intervention. Interventions could include pharmacological (e.g. laxatives) and non-pharmacological interventions (e.g. acupuncture, educational and behavioural interventions).We included quasi-randomised trials. Cluster-RCTs were eligible for inclusion but none were identified. Studies using a cross-over design were not eligible for inclusion in this review., Data Collection and Analysis: Two review authors independently screened the results of the search to select potentially relevant studies, extracted data and assessed risk of bias. Results were pooled in a meta-analysis only where there was no substantial statistical heterogeneity., Main Results: We included five trials (1208 postpartum mothers); four compared a laxative with placebo and one compared a laxative alone versus the same laxative plus a bulking agent in women who underwent surgical repair of third degree perineal tears. Trials were poorly reported and risk of bias was unclear for most domains. Overall, there was a high risk of selection and attrition bias. Laxative versus placeboNone of the four trials included in this comparison assessed any of our pre-specified primary outcomes (pain or straining on defecation, incidence of postpartum constipation or changes in quality of life).All four trials reported time to first bowel movement (not pre-specified in our protocol). In one trial, more women in the laxative group had their first bowel movement less than 24 hours after delivery compared to women in the placebo group (risk ratio (RR) 2.90, 95% confidence interval (CI) 2.24 to 3.75, 471 women). Individual trials also reported inconsistent results for days one, two and three after delivery. Pooled results of two trials showed that fewer women in the laxative group were having their first bowel movement at day four compared with controls (average RR 0.36, 95% CI 0.21 to 0.61, 671 women).Regarding secondary outcomes, no trials reported on stool consistency using the Bristol stool form scale orrelief of abdominal pain/discomfort . One trial reported the number of women having loose or watery stools and there were more women who experienced this in the laxative group compared to the placebo group (RR 26.96, 95% CI 3.81 to 191.03, 106 women). One trial found no clear difference in the number of enemas between groups (RR 0.63, 95% CI 0.38 to 1.05, 244 women). One trial reported more women having more than two bowel movements per day in the laxative compared to the placebo group (RR 26.02, 95% CI 1.59 to 426.73, 106 women). Adverse effects were poorly reported; two trials reported the number of women having abdominal cramps, but their results could not be pooled in a meta-analysis due to substantial statistical heterogeneity. In one trial, more women in the laxative group had abdominal cramps compared to the placebo group (RR 4.23, 95% CI 1.75 to 10.19, 471 women), while the other trial showed no difference between groups (RR 0.25, 95% CI 0.03 to 2.20, 200 women). With regards to adverse effects of the intervention on the baby , one trial found no difference in the incidence of loose stools (RR 0.62, 95% CI 0.16 to 2.41, 281 women) or diarrhoea (RR 2.46, 95% CI 0.23 to 26.82, 281 women) between the two groups. Laxative versus laxative plus bulking agentOnly one trial was included in this comparison and reported on pain or straining on defecation in women who underwent surgical repair of third degree perineal tears; there was no reported difference between groups (median (range) data only). No difference was reported in the incidence of postpartum constipation (data not reported) and the outcome changes in quality of life was not mentioned.Time to first bowel movement was reported as a median (range) with no difference between the two groups. In terms of adverse effects , women in the laxative plus stool-bulking group were reported to be at a greater risk of faecal incontinence during the immediate postpartum period (median (range) data only). However the number of women having any episode of faecal incontinence during first 10 days postpartum was reported with no clear difference between the two groups (14/77 (18.2%) versus 23/70 (32.9%), RR 0.55, 95% CI 0.31 to 0.99, 147 women). The trial did not report on adverse effects of the intervention on the babies.The trial reported none of the following pre-specified secondary outcomes: stool consistency using Bristol stool form scale , use of alternative products , laxative agents , enemas , relief of abdominal pain/discomfort and stool frequency ., Authors' Conclusions: We did not identify any trials assessing educational or behavioural interventions. We identified four trials that examined laxatives versus placebo and one that examined laxatives versus laxatives plus stool bulking agents. Results from trials were inconsistent and there is insufficient evidence to make general conclusions about the effectiveness and safety of laxatives.Further rigorous trials are needed to assess the effectiveness and safety of laxatives during the postpartum period for preventing constipation. Trials assessing educational and behavioural interventions and positions that enhance defecation are also needed. Future trials should report on the following important outcomes: pain or straining on defecation; incidence of postpartum constipation, quality of life, time to first bowel movement after delivery, and adverse effects caused by the intervention such as: nausea or vomiting, pain and flatus.

Background: Constipation is a functional bowel disorder that can reduce quality of life in the puerperium period. The diagnosis of postpartum constipation is both subjective and objective. It is characterised by symptoms such as pain or discomfort, straining, hard lumpy stools and a sense of incomplete bowel evacuation. Haemorrhoids, pain at the episiotomy site, effects of pregnancy hormones and hematinics used in pregnancy can increase the risk of postpartum constipation. Although a high fibre diet and increased fluid intake is encouraged to assist defecation in the puerperium, pain-relieving drugs and laxatives are common drugs of choice to alleviate constipation. However, the effectiveness and safety of laxatives on the nursing mother need to be ascertained., Objectives: To evaluate the effectiveness of interventions for treating postpartum constipation., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 March 2014), the metaRegister of Controlled Trials, the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov), the Australian New Zealand Clinical Trials Registry (ANZCTR), the World Health Organization International Clinical Trials Registry platform (ICTRP), the ProQuest database, Stellenbosch University database and Google Scholar (28 March 2014). We also searched the reference lists of potentially relevant studies identified by the search, reviewed articles for relevant trials and contacted experts to identify any additional published or unpublished trials (10 April 2014)., Selection Criteria: All randomised controlled trials comparing any intervention for the treatment of postpartum constipation to another intervention, placebo or no intervention.Interventions could include laxatives, surgery, as well as educational and behavioural interventions., Data Collection and Analysis: Two review authors independently screened the results of the search to select potentially relevant studies using pre-designed eligibility inclusion criteria. Discrepancies were resolved through discussion. We did not identify any studies for inclusion., Main Results: We did not identify any studies that met our inclusion criteria. We excluded nine studies., Authors' Conclusions: We could not make explicit conclusions on interventions for treating postpartum constipation because we found no studies for inclusion in this review. Rigorous and well-conducted large randomised controlled trials aimed at treating postpartum women diagnosed with constipation would be beneficial. These trials should also address the criteria for administering the intervention (time and stage of a diagnosis of postpartum constipation), and the safety and effectiveness of such interventions.