Estimating the burden of disease attributable to ambient air pollution (ambient PM2.5 and ambient ozone) in South Africa for 2000, 2006 and 2012.

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.

Overview.

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.

Three-dimensional microscale hanging drop arrays with geometric control for drug screening and live tissue imaging.

Existing three-dimensional (3D) culture techniques are limited by trade-offs between throughput, capacity for high-resolution imaging in living state, and geometric control. Here, we introduce a modular microscale hanging drop culture where simple design elements allow high replicates for drug screening, direct on-chip real-time or high-resolution confocal microscopy, and geometric control in 3D. Thousands of spheroids can be formed on our microchip in a single step and without any selective pressure from specific matrices. Microchip cultures from human LN229 glioblastoma and patient-derived mouse xenograft cells retained genomic alterations of originating tumors based on mate pair sequencing. We measured response to drugs over time with real-time microscopy on-chip. Last, by engineering droplets to form predetermined geometric shapes, we were able to manipulate the geometry of cultured cell masses. These outcomes can enable broad applications in advancing personalized medicine for cancer and drug discovery, tissue engineering, and stem cell research.

Cost-effectiveness of radioguided occult lesion localization using 125I seeds versus hookwire localization before breast-conserving surgery for non-palpable breast cancer.

BACKGROUND: The aim was to determine the cost-effectiveness of radioguided occult lesion localization using 125I-labelled seeds (125I seeds) versus hookwire localization in terms of incremental cost per reoperation avoided for women with non-palpable breast cancer undergoing breast-conserving surgery. METHODS: This study was based on a multicentre RCT with eight study sites comprising seven public hospitals and one private hospital. An Australian public health system perspective was taken. The primary effectiveness outcome for this study was reoperations avoided. Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to explore uncertainty. The willingness to pay (additional cost of localization using 125I seeds justified by reoperation cost avoided) was set at the weighted, top-down cost of reoperation. Costs were in 2019 Australian dollars ($1 was equivalent to €0.62). RESULTS: The reoperation rate was 13.9 (95 per cent confidence interval 10.7 to 18.0) per cent for the 125I seed group and 18.9 (14.8 to 23.8) per cent for the hookwire localization group. The ICER for 125I seed versus hookwire localization was $4474 per reoperation averted. The results were most sensitive to uncertainty around the probability of reoperation. Accounting for transition probability and cost uncertainty for 125I seed localization, there was a 77 per cent probability that using 125I seeds would be cost-effective, with a willingness to pay of $7693 per reoperation averted. CONCLUSION: Radioguided occult lesion localization using 125I seeds is likely to be cost-effective, because the marginal (additional) cost compared with hookwire localization is less than the cost of reoperations avoided.

Damage control resuscitation and surgery for indigenous combat casualties: a prospective observational study.

INTRODUCTION: Specialist units that assist indigenous forces (IF) in their strategic aims are supported by medical teams providing point of injury emergency care for casualties, including IF and civilians (Civ). We investigated the activities of a Coalition Forces far-forward medical facility, in order to inform medical providers about the facilities and resources required for medical support to IF and Civ during such operations. METHODS: A prospective observational study (June to August 2017) undertaken at a far-forward Coalition Forces medical support unit (12 rotating personnel) recorded patient details (IF or Civ), mechanism of injury (MOI), number of blood products used, damage control resuscitation (DCR) and damage control surgery (DCS), number of mass casualty (MASCAL) scenarios, resuscitative thoracotomy, resuscitative endovascular balloon occlusion of the aorta (REBOA) and whole blood emergency donor panels (EDP). RESULTS: 680 casualties included 478 IF and 202 Civ (45.5% of the Civ were paediatric). Most common MOIs were blast (n=425; 62.5%) and gunshot wound (n=200; 29.4%). Fifteen (2.2%) casualties died; 627 (92.2%) were transferred to local hospitals. DCR was used for 203 (29.9%), and DCS for 182 (26.8%) casualties. There were 23 MASCAL scenarios, 1220 transfusions and 32 EDPs. REBOA was performed eight times, and thoracotomy was performed 27 times. CONCLUSIONS: A small medical team provided high-tempo emergency resuscitative care for hundreds of IF and Civ casualties within a short space of time using state-of-the-art resuscitative modalities. DCR and DCS were undertaken with a large number of EDPs, and a high survival-to-transfer rate.

Toxicological analysis of aerosols derived from three electronic nicotine delivery systems using normal human bronchial epithelial cells.

Electronic nicotine delivery systems (ENDS) are a rapidly growing global market advertised as a safer alternative to combustible cigarettes. However, comprehensive investigations of END aerosol physicochemical and toxicological properties have not been fully explored across brands to assess relative safety. In this study, we evaluated aerosols collected from three ENDS - Juul Fruit Medley (5% nicotine), Logic Power (2.4% nicotine), and Mistic (1.8% nicotine). ENDS aerosols were generated using standard machine puffing regimen and collected with a novel fluoropolymer condensation trap. Triple quadrupole-inductively coupled plasma-mass determined the presence of heavy metals in collected aerosols. The toxicological effects of ENDS aerosols on normal human bronchial epithelial cells (NHBE) were investigated using cellular viability, reactive oxygen species, oxidative stress assays, along with DNA damage assessments using the CometChip©. Results indicated the total metal concentrations within collected ENDS aerosols were higher for Mistic and Logic compared to Juul. Logic Power aerosols elicited higher reactive oxygen species levels than Mistic and Juul in NHBE after 24-h exposure. Similar dose-dependent reductions of cellular viability and total glutathione were found for each exposure. However, Logic and Juul aerosols caused greater single stranded DNA damage compared to Mistic. Our study indicates that regardless of brand, ENDS aerosols are toxic to upper airway epithelial cells and may pose a potential respiratory hazard to occasional and frequent users.

Associations of Perirenal Fat Thickness with Renal and Systemic Calcified Atherosclerosis.

BACKGROUND: We investigated associations between perirenal fat thickness and atherosclerotic calcification in six different vascular beds. METHODS: Using a community-based cohort (n=3,919), perirenal fat thickness was estimated from computed tomography scans. It was classified as Q1 (the lowest quartile) to Q4 (the highest quartile) in each sex. Calcification in the carotid arteries, coronary arteries, thoracic aorta, abdominal aorta, iliac arteries, and renal arteries was evaluated. RESULTS: Perirenal fat thickness was associated with older age (P<0.01) and a higher prevalence of obesity, hypertension, and dyslipidemia (P<0.01 for all). Perirenal fat thickness was independently associated with renal arterial calcification even after adjustment for age, sex, body mass index, hypertension, dyslipidemia, smoking history, and family history of heart diseases in first-degree relatives (odds ratio [OR] per quartile of perirenal fat thickness, 1.25; 95% confidence interval [CI], 1.09 to 1.44). Compared to Q1, the odds of renal arterial calcification in Q4 was about two times higher (OR, 2.05; 95% CI, 1.29 to 3.25). After adjustment for renal arterial calcification and atherosclerotic risk factors, the only other vascular bed where perirenal fat thickness showed a significant association with calcification was the abdominal aorta (OR, 1.11; 95% CI, 1.00 to 1.23; P=0.045). CONCLUSION: Perirenal fat thickness was independently associated with vascular calcification in the renal artery and abdominal aorta.

The association between liver fat and systemic calcified atherosclerosis.

BACKGROUND: The association of nonalcoholic fatty liver disease (NAFLD) with systemic calcified atherosclerosis, other than the coronary arteries, has not been clearly elucidated. We investigated the association between NAFLD and calcification in eight different vascular beds. METHODS: In a community-based cohort with computed tomography scans for carotid artery, coronary artery, thoracic aorta, abdominal aorta, iliac artery, renal artery, celiac trunk, and superior mesenteric artery, the association between NAFLD and arterial calcification was evaluated with adjustment for age, sex, hypertension, dyslipidemia, diabetes, obesity, current smoking status, and family history of heart disease in the first-degree relatives. RESULTS: In age- and sex-adjusted models, NAFLD was significantly associated with calcification in the coronary artery, carotid artery, thoracic aorta, celiac trunk, and superior mesenteric artery vascular beds (P < .05). However, adjustment for the traditional chronic venous disease risk factors attenuated the associations, except in the case of the thoracic aorta (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.09-1.78) and celiac trunk (OR, 2.05; 95% CI, 1.16-3.65). In addition, NAFLD was independently associated with multiarterial calcification (four or more [OR, 1.33; 95% CI, 1.01-1.74], five or more [OR, 1.46; 95% CI, 1.09-1.97], and six or more [OR, 1.58; 95% CI, 1.09-2.30] of eight evaluated arterial segments). CONCLUSIONS: The association between NAFLD and arterial calcification is mainly mediated by conventional risk factors. The independent association between NAFLD and calcification in the thoracic aorta and celiac trunk as well as in a larger number of vascular beds needs confirmation in future prospective studies in diverse populations.

For debate: on-the-person battlefield antibiotics.

Wound infection has always been an important contributor to mortality and morbidity on the battlefield. On-the-person antibiotics have long been suggested as one way to help combat this, which have already been implemented by some North Atlantic Treaty Organization partners. This paper is an up-to-date review of the evidence of the efficacy of on-the-person antibiotics and whether the British military should look to use them in the near future.

The incidence of melanoma in South Africa: An exploratory analysis of National Cancer Registry data from 2005 to 2013 with a specific focus on melanoma in black Africans.

BACKGROUND: Melanoma is an aggressive skin cancer with poor survival when diagnosed late. There are important differences in clinical and histological features of melanoma and disease outcomes in people with darker skin types. METHODS: A retrospective review of data captured by the National Cancer Registry (NCR) of South Africa (SA) was performed for 2005 - 2013. Data on patient numbers, demography, location and biological features were analysed for all records. Closer analysis of melanoma of the limbs reported in black Africans was done after manually collecting this information from original reports. RESULTS: With 11 784 invasive melanomas reported to the NCR, the overall incidence of melanoma for SA was 2.7 per 100 000. Males (51%), individuals aged ≥60 years (48%) and the anatomical sites of lower limb (36%) and trunk (27%) were most commonly affected. Melanoma incidences in the white and black populations were 23.2 and 0.5 per 100 000, respectively. Most cases were diagnosed at private pathology laboratories (73%). Superficial spreading melanoma (47%) and nodular melanoma (20%) predominated. Among 878 black Africans diagnosed in the public sector with melanoma of the limbs, females (68%) and individuals aged ≥60 years (61%) were most commonly affected. Lower-limb lesions (91%) and acral lentiginous melanoma (65%) predominated, with 74% of cases affecting the foot and 62% of cases presenting with a Breslow depth >4 mm. CONCLUSIONS: This study provides up-to-date NCR incidence and demographic data on melanoma and highlights the neglected research gaps in relation to melanoma in black Africans to provide evidence needed to address health disparities in overlooked population groups.

Neonatal, infant and child health in South Africa: Reflecting on the past towards a better future.

Although the neonatal mortality rate in South Africa (SA) has remained stagnant at 12 deaths per 1 000 live births, the infant and under-5 mortality rates have significantly declined since peaking in 2003. Policy changes that have influenced this decline include policies to prevent vertical HIV transmission, earlier treatment of children living with HIV, expanded immunisation policies, strengthening breastfeeding practices, and health policies to contain tobacco and sugar use. The Sustainable Development Goals (2016 - 2030) have shifted the focus from keeping children alive, as expressed in the Millennium Development Goals (1990 - 2015), to achieving optimal health through the 'Survive, thrive and transform' global agenda. This paper focuses on important remaining causes of childhood mortality and morbidity in SA, specifically respiratory illness, environmental pollution, tuberculosis, malnutrition and vaccine-preventable conditions. The monitoring of maternal and child health (MCH) outcomes is crucial, and has improved in SA through both the District Health Information and Civil Registration and Vital Statistics systems, although gaps remain. Intermittent surveys and research augment the routinely collected data. However, availability and use of local data to inform quality and effectiveness of care is critical, and this requires ownership at the collection point to facilitate local redress. Potential game changers to improve MCH outcomes include mobile health and community-based interventions. In SA, improved MCH remains a crucial factor for human capital development. There is a pressing need to focus beyond childhood mortality and to ensure that each child thrives.

Association between Degree of Anaplasia and Degree of Inflammation with the Expression of COX-2 in Feline Injection Site Sarcomas.

Feline injection site sarcomas (FISSs) are mesenchymal neoplasms that develop at the sites of delivery of vaccines or other injectable products. Vaccine adjuvants can trigger an intense and persistent inflammatory response that may lead to neoplastic transformation. The proinflammatory role of cyclo-oxygenase (COX)-2 is well known and its overexpression has prognostic value in multiple neoplastic processes. One hundred and seventeen FISSs were evaluated for the degree of inflammation and anaplasia. Immunohistochemistry was used to determine the expression of COX-2 in these sarcomas. There was a significant association between the degree of inflammation and the expression of COX-2 by neoplastic cells. COX-2 expression was lower in tumours with higher degrees of anaplasia. These findings may be useful in predicting the sensitivity of FISSs to treatment with COX-2 inhibitors. The potential therapeutic use of such agents could then be restricted to tumours with lower degrees of anaplasia.

Assessing a portable, real-time display handheld meter with UV-A and UV-B sensors for potential application in personal sun exposure studies.

BACKGROUND: Observing accurate real-time measurements of solar ultraviolet radiation (UVR) levels is important since personal excess sun exposure is associated with skin cancers. Handheld measurement devices may be helpful but their accuracy is unknown. We compare a portable, science-grade solar UVR monitoring device against two fixed, science-grade solar UVR instruments. METHODS: Instruments were (1) a fixed Solar Light 501 UV-B biometer to measure UV-B; (2) a fixed Kipp and Zonen radiometer used to measure UV-A and UV-B; and (3) Goldilux ultraviolet probes which are commercially available portable devices. Two different probes were used, one measured UV-A and the other UV-B radiation. The Goldilux probes were levelled and secured next to the UV-B biometer. Between 10:00 and 14:40 UTC+2, the UV-B biometer was set to record at 10-minute intervals and measurements by the Goldilux probes were manually taken simultaneously. Results were compared for all data and by solar zenith angle (SZA) ranges. RESULTS: The Goldilux UV-B probe measured UV-B relatively well in its diurnal pattern, however, its readings were ~77% higher than those made by the UV-B biometer. While UV-A measurements from the Goldilux UV-A probe and those from the radiometer were in relatively good agreement in pattern, the radiometer read ~47% higher than the Goldilux UV-A probe. UV-B data from Goldilux UV-B probe had a moderately strong correlation with UV-B biometer data for small SZAs; conversely, for UV-A, the Goldilux UV-A probe had a strong correlation with the UV-A radiometer data for large SZAs. CONCLUSION: Handheld devices may be useful to provide real-time readings of solar UVR patterns, however, to achieve synchronicity in the magnitude of readings to those made by science-grade fixed instruments, devices may need to be used during certain times of the day and in clear-sky conditions which may not be practical in personal exposure studies.

Superior mesenteric artery calcification is associated with cardiovascular risk factors, systemic calcified atherosclerosis, and increased mortality.

BACKGROUND: Atherosclerosis is a major risk factor for morbidity and mortality. However, epidemiologic data are sparse regarding risk factors for superior mesenteric artery calcification (SMAC), the association between SMAC and disease in other arterial beds, or the independent contribution of SMAC to risk of mortality. The objective of this study was to test the hypothesis that presence and extent of SMAC are associated with cardiovascular disease (CVD) risk factors, calcification in other arterial beds, and both cardiovascular and all-cause mortality, independent of classic risk factors and calcification in other arterial beds. METHODS: Arterial calcification in the superior mesenteric artery, celiac trunk, coronaries, thoracic aorta, abdominal aorta, and iliac arteries was evaluated by computed tomography in adults with no known CVD. Multiple logistic regression models examined risk factor associations for SMAC and SMAC as a risk factor for calcification in other arterial beds. Cox models were used to examine the association between SMAC and mortality. RESULTS: The average age of subjects was 56 years; 43.7% (1877/4300) were women, and 6.7% (290) had SMAC. Age (odds ratio [OR], 1.09; 95% confidence interval, 1.06-1.11), male sex (OR, 1.79; 95% CI, 1.08-3.03), dyslipidemia (OR, 1.38; 95% CI, 1.01-1.88), and any smoking (OR, 1.60; 95% CI, 1.20-2.14) were associated with SMAC presence. Notably, body mass index, body fat percentage, hypertension, diabetes, and family history of coronary heart disease were not significant risk factors for the presence of SMAC. SMAC presence was associated with calcification in all five other arterial beds (OR, 6.02; 95% CI, 3.76-9.66). During a median follow-up time of 9.4 years, there were 234 deaths, 76 of which were CVD related. SMAC extent (represented as per-unit increase in log [SMAC score + 1]; OR, 1.31; 95% CI, 1.01-1.71) was significantly associated with CVD mortality after full adjustment for risk factors and calcification in other arterial beds. SMAC presence (OR, 1.52; 95% CI, 1.10-2.12) and extent (OR, 1.25; 95% CI, 1.06-1.48) were also both significantly associated with all-cause mortality after full adjustment. CONCLUSIONS: SMAC is associated with specific CVD risk factors as well as with calcification in all other arterial beds. SMAC extent was significantly associated with incident cardiovascular mortality, whereas both SMAC presence and extent were significantly associated with all-cause mortality, even after adjustment for risk factors and calcification in other arterial beds. Further studies are needed to determine whether SMAC is simply a marker for advanced and systemic disease or whether it confers increased mortality risk through an independent mechanism.

Occupational burnout among radiation therapists in Australia: Findings from a mixed methods study.

INTRODUCTION: Evidence demonstrates that health care professionals in the palliative care context are more burned out than other health professionals. The aims of this study were to examine: (1) occupational burnout levels among radiation therapists in Australia, (2) association between demographic factors on burnout and (3) radiation therapists' perceptions of burnout. METHODS: A cross-sectional online survey including the Maslach Burnout Inventory was administered to Radiation Therapists in Australia. Data were analysed using SPSS Ver 20 and open ended comments were analysed thematically using Nvivo 10. RESULTS: A total of 200 radiation therapists participated in the survey. RTs had a high mean (±SD) burnout score for emotional exhaustion (38.5 ± 8.2), depersonalisation (17.5 ± 4.7) and personal achievement (30.5.3 ± 4.3) compared to RTs and health workers in other studies. High levels of emotional exhaustion, depersonalisation and low levels of personal achievement were present in 93% (186/200), 87% (174/200) and 61% (122/200) of participants respectively. RTs identified high workload and staff shortages, interpersonal conflict and technology as key sources of stress in the RT work environment. CONCLUSION: Australian RTs' level of burnout on all three stages of burnout exceed previously reported burnout levels for similar cohorts both locally and internationally. It is important that future interventions aimed at minimising or preventing stressors are identified and implemented in the radiation therapy work environment.