Craig Hansen

Spectrum of heart disease and risk factors in a black urban population in South Africa (the Heart of Soweto Study): a cohort study

BACKGROUND The Heart of Soweto Study aims to increase our understanding of the characteristics and burden imposed by heart disease in an urban African community in probable epidemiological transition. We aimed to investigate the clinical range of disorders related to cardiovascular disease in patients presenting for the first time to a tertiary-care centre. METHODS From Jan 1 to Dec 31, 2006, we recorded data for 4162 patients with confirmed cases of cardiovascular disease (1593 newly diagnosed and 2569 previously diagnosed and under treatment) who attended the cardiology unit at the Chris Hani Baragwanath Hospital in Soweto, South Africa. We developed a prospectively designed registry and gathered detailed clinical data relating to the presentation, investigations, and treatment of all 1593 patients with newly diagnosed cardiovascular disease. FINDINGS Most patients were black Africans (n=1359 [85%]), and the study population contained more women (n=939 [59%]) than men. Women were slightly younger than were men (mean 53 [SD 16] years vs 55 [15] years; p=0.031), with 399 (25%) patients younger than 40 years. Heart failure was the most common primary diagnosis (704 cases, 44% of total). Moderate to severe systolic dysfunction was evident in 415 (53%) of 844 identified cases of heart failure, 577 (68%) of which were attributable to dilated cardiomyopathy or hypertensive heart disease, or both. Black Africans were more likely to be diagnosed with heart failure than were the rest of the cohort (739 [54%] vs 105 [45%]; odds ratio [OR] 1.46, 95% CI 1.11-1.94; p=0.009) but were less likely to be diagnosed with coronary artery disease (77 [6%] vs 88 [38%]; OR 0.10, 0.07-0.14; p<0.0001). Prevalence of cardiovascular risk factors was very high, with 897 (56%) patients diagnosed with hypertension (190 [44%] of whom were also obese). Only 209 (13%) patients had no identifiable risk factors, whereas 933 (59%) had several risk factors. INTERPRETATION We noted many threats to the present and future cardiac health of Soweto, including a high prevalence of modifiable risk factors for atherosclerotic disease and a combination of infectious and non-communicable forms of heart disease, with late clinical presentations. Overall, our findings provide strong evidence that epidemiological transition in Soweto, South Africa has broadened the complexity and spectrum of heart disease in this community. This registry will enable continued monitoring of the range of heart disease.

Predominance of Heart Failure in the Heart of Soweto Study Cohort. Emerging Challenges for Urban African Communities

Background— There is a paucity of data to describe the clinical characteristics of heart failure (HF) in urban African communities in epidemiological transition. Methods and Results— Chris Hani Baragwanath Hospital services the 1.1 million black African community of Soweto, South Africa. Of 1960 cases of HF and related cardiomyopathies in 2006, we prospectively collected detailed demographic and clinical data from all 844 de novo presentations (43%). Mean age was 55±16 years, and women (479 [57%]) and black Africans (739 [88%]) predominated. Most (761 [90%]) had ≥1 cardiovascular risk. Mean left ventricular ejection fraction was 45±18%. Overall, 180 patients (23%) had isolated diastolic dysfunction, 234 (28%) tricuspid regurgitation, 121 (14%) isolated right HF, and 100 (12%) mitral regurgitation. The most common diagnoses were hypertensive HF (281 [33%]), idiopathic dilated cardiomyopathy (237 [28%]), and, surprisingly, right HF (225 [27%]). Black Africans had less ischemic cardiomyopathy (adjusted odds ratio, 0.12; 95% CI, 0.07 to 0.20) but more idiopathic and other causes of cardiomyopathy (adjusted odds ratio, 4.80; 95% CI, 2.57 to 8.93). Concurrent renal dysfunction, anemia, and atrial fibrillation were found in 172 (25%), 72 (10%), and 53 (6.3%) cases, respectively. Conclusions— These contemporary data highlight the multiple challenges of preventing and managing an increasing and complex burden of HF in urban Africa. In addition to tackling antecedent hypertension, a predominance of young women and a large component of right HF predicate the development of tailored therapeutic strategies.

Anti-tumour activity in vitro and in vivo of selective differentiating agents containing hydroxamate.

SummaryA series of hydroxamates, which are not metalloprotease inhibitors, have been found to be selectively toxic to a range of transformed and human tumour cells without killing normal cells (fibroblasts, melanocytes) at the same concentrations. Within 24 h of treatment, drug action is characterized by morphological reversion of tumour cells to a more normal phenotype (dendritic morphology), and rapid and reversible acetylation of histone H4 in both tumour and normal cells. Two hydroxamates inhibited growth of xenografts of human melanoma cells in nude mice; resistance did not develop in vivo or in vitro. A third hydroxamate, trichostatin A, was active in vitro but became inactivated and had no anti-tumour activity in vivo. Development of dendritic morphology was found to be dependent upon phosphatase activity, RNA and protein synthesis. Proliferating hybrid clones of sensitive and resistant cells remained sensitive to ABHA, indicating a dominant-negative mechanism of sensitivity. Histone H4 hyperacetylation suggests that these agents act at the chromatin level. This work may lead to new drugs that are potent, and selective anti-tumour agents with low toxicity to normal cells.

The effect of ambient air pollution during early pregnancy on fetal ultrasonic measurements during mid-pregnancy

Background Over the past decade there has been mounting evidence that ambient air pollution during pregnancy influences fetal growth. Objectives This study was designed to examine possible associations between fetal ultrasonic measurements collected from 15,623 scans (13–26 weeks gestation) and ambient air pollution during early pregnancy. Methods We calculated mothers’ average monthly exposures over the first 4 months of pregnancy for the following pollutants: particulate matter < 10 μm aerodynamic diameter (PM10), ozone, nitrogen dioxide, and sulfur dioxide. We examined associations with fetal femur length (FL), biparietal diameter (BPD), head circumference (HC), and abdominal circumference (AC). Final analyses included scans from only those women within 2 km of an air pollution monitoring site. We controlled for long-term trend, season, temperature, gestation, mother’s age, socioeconomic status, and fetal sex. Results A reduction in fetal AC was associated with O3 during days 31–60 [−1.42 mm; 95% confidence interval (CI), −2.74 to −0.09], SO2 during days 61–90 (−1.67 mm; 95% CI, −2.94 to −0.40), and PM10 during days 91–120 (−0.78 mm; 95% CI, −1.49 to −0.08). Other results showed a reduction in BPD (−0.68 mm; 95% CI, −1.09 to −0.27) associated with SO2 during days 0–30, a reduction in HC (−1.02 mm; 95% CI, −1.78 to −0.26) associated with PM10 during days 91–120, and a reduction in FL associated with PM10 during days 0–30 (−0.28 mm; 95% CI, −0.48 to −0.08) and 91–120 (−0.23; 95% CI, −0.42 to −0.04). Conclusion We found strong effects of ambient air pollution on ultrasound measures. Future research, including more individually detailed data, is needed to confirm our results.

How good are skin cancer clinics at melanoma detection? Number needed to treat variability across a national clinic group in Australia.

BACKGROUND The number needed to treat (NNT) is a key measure of the quality of melanoma diagnosis. There are few data on this measure from primary care skin cancer clinics in Australia. OBJECTIVE We sought to report the NNT from a large pathology database and examine several patient characteristics. METHODS We calculated NNT by doctor and clinic among 10,612 lesions, 6796 patients, 57 doctors, and 15 clinics from a pathology database. NNT was calculated with and without seborrheic keratoses. RESULTS Overall NNT was 30 (with seborrheic keratoses) and 23 (without seborrheic keratoses). Excluding the 4 doctors with NNT greater than 60, total NNT decreased from 30 to 21 and from 23 to 15, respectively (with and without seborrheic keratoses). NNT was higher for female patients and younger patients (<30 years). NNT varied by doctor from 0 to 192 and 117, respectively (with and without seborrheic keratoses). LIMITATIONS Given the retrospective design, we were unable to examine doctor characteristics such as age, sex, medical training, and patient pressure to excise. CONCLUSIONS Substantial variability in individual doctor NNT produced an overall NNT similar to that reported from mainstream general practice, and higher than specialist practice.

The clinical consequences and challenges of hypertension in urban-dwelling black Africans: Insights from the Heart of Soweto Study

BACKGROUND There is a paucity of data to describe advanced forms of cardiovascular disease (CVD) in urban black Africans with hypertension (HT). METHODS Chris Hani Baragwanath Hospital services the black African community of 1.1 million people in Soweto, South Africa. We prospectively collected detailed demographic and clinical data from all de novo presentations to the hospitals Cardiology Unit in 2006. RESULTS Overall, 761 black African patients (56% of de novo cases) presented with a diagnosis of HT with more women (63%, aged 58.5±14.9 years) than men (aged 58.0±15.6 years). On presentation, 396 women (82%) versus 187 men (67%) had dizziness, palpitations and/or chest pain (OR 1.23, 95% 1.12-1.34: p<0.0001). HT was the primary diagnosis in 266 cases (35%). In the rest (n=495), non-ischaemic forms of heart failure were common (54% of total) while only 6.2% had coronary artery disease. Concurrent left ventricular hypertrophy, renal dysfunction and anaemia were present in 39%, 24% and 11% of cases, respectively, with a similar age-adjusted pattern of co-morbidity according to sex. However, men were more likely to present with impaired systolic function (OR 2.13, 95% CI 1.50 to 3.00; p<0.0001). CONCLUSIONS In the absence of effective primary and secondary prevention strategies, these unique data highlight the potentially devastating impact of advanced forms of hypertensive heart disease in urban black African communities with more women than men affected.

Factors contributing to incomplete excision of nonmelanoma skin cancer by Australian general practitioners

OBJECTIVE To study rates of incomplete excision of basal (BCC) and squamous (SCC) cell cancer by Australian general practitioners with a special interest. DESIGN Records review. SETTING A network of 15 primary care skin cancer clinics across Australia. PARTICIPANTS Fifty-seven physicians performing excisions of 9417 BCCs and SCCs in a single network of 15 primary care skin cancer clinics across Australia between 2005 and 2007. MAIN OUTCOME MEASURES Rates of incomplete excision according to physician, clinic, anatomic location of the lesion, and whether a previous biopsy had been performed. RESULTS Four hundred forty-three of 6881 BCCs (6.4%) and 159 of 2536 SCCs (6.3%) were excised incompletely. Incomplete BCC and SCC excisions were more frequent on the head and neck (282 of 2872 excisions [9.8%] and 97 of 861 [11.3%], respectively) than elsewhere. Ears (74 of 388 excisions [19.1%]) and nose (78 of 546 [14.3%]) had the highest rates of incompletely excised BCCs, and ears (26 of 144 excisions [18.1%]) and forehead (20 of 157 [12.7%]) had the highest rates of incompletely excised SCCs. Of all BCC excisions, 67.3% were once-off excisions with no previous biopsy, and these excisions were more likely to be incomplete (odds ratio, 1.73; 95% confidence interval, 1.36-2.20) than those with a previous biopsy. There was, however, substantial variation in frequency of incomplete excision between clinics for BCC (ranging from 3.3% to 24.7%) and SCC (ranging from 0% to 17.2%) and between physicians within clinics (BCC ranging from 0% to 31.1%, and SCC ranging from 0% to 23.5%). CONCLUSIONS Overall frequency of incomplete excision is low and similar to that in other reports. However, high frequency in high-risk sites, low rates of previous biopsy, and substantial variation in performance between physicians and clinics suggests there is significant opportunity to further improve health outcomes.

Increased traffic exposure and negative birth outcomes: a prospective cohort in Australia

BackgroundPregnant women exposed to traffic pollution have an increased risk of negative birth outcomes. We aimed to investigate the size of this risk using a prospective cohort of 970 mothers and newborns in Logan, Queensland.MethodsWe examined two measures of traffic: distance to nearest road and number of roads around the home. To examine the effect of distance we used the number of roads around the home in radii from 50 to 500 metres. We examined three road types: freeways, highways and main roads.ResultsThere were no associations with distance to road. A greater number of freeways and main roads around the home were associated with a shorter gestation time. There were no negative impacts on birth weight, birth length or head circumference after adjusting for gestation. The negative effects on gestation were largely due to main roads within 400 metres of the home. For every 10 extra main roads within 400 metres of the home, gestation time was reduced by 1.1% (95% CI: -1.7, -0.5; p-value = 0.001).ConclusionsOur results add weight to the association between exposure to traffic and reduced gestation time. This effect may be due to the chemical toxins in traffic pollutants, or because of disturbed sleep due to traffic noise.

Measuring performance in skin cancer practice: The SCARD initiative

Background  The Skin Cancer College of Australia and New Zealand (SCCANZ) has developed a unique project named SCARD – the Skin Cancer Audit and Research Database. Designed initially as a self‐audit tool for primary care skin cancer practitioners, SCARD acts as a tracking tool to enhance practice safety, and it also creates practice performance reports. Pooling of de‐identified data enables participating practitioners to confidentially compare their own practice to that of their peers. Additionally, this creates a large database with significant research potential, as SCARD records for every lesion de‐identified practitioner and patient data, and extensive details of location, provisional and histological diagnosis, and the procedure(s) performed in its treatment.

Exposure to mobile source air pollution in early life and childhood asthma incidence: The Kaiser Air Pollution and Pediatric Asthma Study

Background: Early-life exposure to traffic-related air pollution exacerbates childhood asthma, but it is unclear what role it plays in asthma development. Methods: The association between exposure to primary mobile source pollutants during pregnancy and during infancy and asthma incidence by ages 2 through 6 was examined in the Kaiser Air Pollution and Pediatric Asthma Study, a racially diverse birth cohort of 24,608 children born between 2000 and 2010 and insured by Kaiser Permanente Georgia. We estimated concentrations of mobile source fine particulate matter (PM2.5, µg/m3), nitrogen oxides (NOX, ppb), and carbon monoxide (CO, ppm) at the maternal and child residence using a Research LINE source dispersion model for near-surface releases. Asthma was defined using diagnoses and medication dispensings from medical records. We used binomial generalized linear regression to model the impact of exposure continuously and by quintiles on asthma risk. Results: Controlling for covariates and modeling log-transformed exposure, a 2.7-fold increase in first year of life PM2.5 was associated with an absolute 4.1% (95% confidence interval, 1.6%, 6.6%) increase in risk of asthma by age 5. Quintile analysis showed an increase in risk from the first to second quintile, but similar risk across quintiles 2–5. Risk differences increased with follow-up age. Results were similar for NOX and CO and for exposure during pregnancy and the first year of life owing to high correlation. Conclusions: Results provide limited evidence for an association of early-life mobile source air pollution with childhood asthma incidence with a steeper concentration–response relationship observed at lower levels of exposure.