Estimating the changing disease burden attributable to smoking in South Africa for 2000, 2006 and 2012.

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.

A cross-sectional observational study of endotracheal intubation and extubation practices among doctors treating adult COVID-19 and suspected COVID-19 patients in South Africa.

BACKGROUND: Patients with severe COVID-19 may require endotracheal intubation. Unique adjustments to endotracheal intubation and extubation practices are necessary to decrease the risk of SARS-CoV-2 transmission to healthcare workers (HCWs) while avoiding complications of airway management. OBJECTIVES: To investigate the practice of endotracheal intubation and extubation, resources available and complications encountered by clinicians performing endotracheal intubation and extubation of COVID-19 and suspected COVID-19 patients in South Africa (SA). METHOD: A cross-sectional observational study was conducted during the initial surge of COVID-19 cases in SA. Data were collected by means of a self-administered questionnaire completed by clinicians in the private and public healthcare sectors after performing an endotracheal intubation and/or extubation of a patient with confirmed or suspected COVID-19. RESULTS: Data from 135 endotracheal intubations and 45 extubations were collected. Anaesthetists accounted for 87.0% (n=120) of the study participants, specialist clinicians in their respective fields for 59.4% (n=82), and public HCWs for 71.0% (n=98). Cases from Gauteng Province made up 76.8% (n=106) of the database. Haemoglobin desaturation was the most frequent complication encountered during endotracheal intubation (40.0%; n=54). Endotracheal intubations performed at private healthcare institutions were associated with a significantly lower complication rate of 17.5% (n=7) compared with 52.6% (n=50) in the public healthcare sector (p<0.001). Endotracheal intubations performed in theatre had the lowest complication rate of 10.4% (n=5; p<0.001). Propofol was used in 90 endotracheal intubations (66.7%), and its use was associated with fewer complications relative to other induction agents. Minimising the number of intubation attempts (p=0.009) and the use of checklists (p=0.013) significantly reduced the frequency of complications encountered during endotracheal intubation. Intravenous induction technique, neuromuscular blocking agent used, intubating device used and time at which intubation was performed did not affect the incidence of complications. The majority of endotracheal extubations were uncomplicated (88.9%). CONCLUSIONS: The study provides valuable insight into the resources used by clinicians and complications encountered when endotracheal intubations and/or extubations were performed. Data from this study may be used to guide future clinical practice and research, especially in resource-limited settings.

SARS-CoV-2 infection prevalence in healthcare workers and administrative and support staff: The first-wave experience at three academic hospitals in the Tshwane district of Gauteng Province, South Africa.

BACKGROUND: The availability of well and functional healthcare workers (HCWs) and support staff is pivotal to a country's ability to manage the COVID-19 pandemic effectively. While HCWs have been identified as being at increased risk for acquisition of SARS-CoV-2 infection, there is a paucity of data pertaining to South African (SA) HCW-related infection rates. Global and provincial disparities in these numbers necessitate local data in order to mitigate risks. OBJECTIVES: To ascertain the overall SARS-CoV-2 infection rates and outcomes among all hospital staff at three hospitals in the Tshwane district of Gauteng Province, SA, and further determine associations with the development of severe COVID-19 disease. METHODS: This retrospective audit was conducted across three academic hospitals in the Tshwane district for the period 1 June - 31 August 2020. Deidentified data from occupational health and safety departments at each hospital were used to calculate infection rates. A more detailed analysis at one of the three hospitals included evaluation of demographics, work description, possible source of SARS-CoV-2 exposure (community or hospital), comorbidities and outcomes. RESULTS: The period prevalence of SARS-CoV-2 infections ranged from 6.1% to 15.4% between the three hospitals, with the average period prevalence being 11.1%. The highest incidence of SARS-CoV-2 infections was observed among administrative staff (2.8 cases per 1 000 staff days), followed by nursing staff (2.7 cases per 1 000 staff days). Medical doctors had the lowest incidence of 1.1 cases per 1 000 staff days. SARS-CoV-2 infections were categorised as either possibly community or possibly healthcare facility acquired for 26.6% and 73.4% of the infections, respectively. The administrative group had the highest proportion of possible community-acquired infections (41.8%), while doctors had the lowest (6.1%). The mean age of individuals with mild and severe disease was 41 years and 46.1 years, respectively (p=0.004). The presence of comorbidities was significantly associated with severity of disease (p=0.002). CONCLUSIONS: This study highlights that hospital staff, including administrative staff, are clearly at high risk for acquisition of SARS-CoV-2 infection during a surge.

Modelling Representative Population Mobility for COVID-19 Spatial Transmission in South Africa.

The COVID-19 pandemic starting in the first half of 2020 has changed the lives of everyone across the world. Reduced mobility was essential due to it being the largest impact possible against the spread of the little understood SARS-CoV-2 virus. To understand the spread, a comprehension of human mobility patterns is needed. The use of mobility data in modelling is thus essential to capture the intrinsic spread through the population. It is necessary to determine to what extent mobility data sources convey the same message of mobility within a region. This paper compares different mobility data sources by constructing spatial weight matrices at a variety of spatial resolutions and further compares the results through hierarchical clustering. We consider four methods for constructing spatial weight matrices representing mobility between spatial units, taking into account distance between spatial units as well as spatial covariates. This provides insight for the user into which data provides what type of information and in what situations a particular data source is most useful.

The epidemiology of traumatic brain injuries sustained by children under 10 years of age presenting to a tertiary hospital in Soweto, South Africa.

BACKGROUND: Traumatic brain injury (TBI) in the paediatric population is a significant contributor to death and disability worldwide. In sub-Saharan Africa, death and disability from TBI are still superseded by infectious disease. Mechanisms of injury differ by region and socioeconomics, but in general, falls, road traffic collisions (RTCs), being 'struck by/against objects' and non-accidental injuries (NAIs) are responsible for most cases. OBJECTIVES: To: (i) quantify the burden of TBI in terms of demographics, causes and severity; (ii) explore resource utilisation regarding length of stay, computed tomography (CT) brain scan use and multidisciplinary participation; (iii) interrogate possible temporal patterns of injury; and (iv) thus identify potential targets for community-based prevention strategies. METHODS: In a 5-year retrospective review of all children aged <10 years admitted with TBI between September 2013 and August 2018, demographics, date of injury, mechanism of injury, severity of TBI based on the Glasgow Coma Scale, and requirement for a CT brain scan were collected for each patient. Outcomes were reported as discharge, transfer or death. Outcomes for children sustaining isolated TBI were compared with those for children sustaining TBI with polytrauma. RESULTS: A total of 2 153 patients were included, with a mean (standard deviation) age of 4.6 (2.7) years and a male/female ratio of 1.7:1. RTCs were the most frequent cause of injury at 59% (80% of these were pedestrian-vehicle collisions), followed by falls at 24%. Mild TBIs accounted for 87% of admissions, moderate injuries for 6%, and severe injuries for 7%. Polytrauma was associated with increased severity of TBI. The cohort had a 2.3% mortality. NAIs accounted for 6% of injuries and carried a 4% mortality. The median (interquartile range) duration of hospitalisation was 1 (1 - 3) days, ranging from <24 hours to 132 days. CT scans were performed on 43% of admitted patients, and 48% of patients had consultations with another medical or allied medical discipline. Injuries were more frequent during the summer months and over weekends. Infants aged <1 year were identified as a group particularly vulnerable to injury, specifically NAI. CONCLUSIONS: Paediatric TBI was demonstrated to be a resource-intensive public health concern. From the results, we identified potential primary prevention targets that could perhaps be incorporated into broader community-based intervention programmes. We also identified a need to study long-term consequences of mild TBI further in our paediatric population.

Managing multidrug-resistant tuberculosis in South Africa: a budget impact analysis.

SETTING: In South Africa prior to 2016, the standard treatment regimen for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) was 24 months long and required daily injectable aminoglycoside (IA) treatment during the first 6 months. Recent evidence supports the replacement of IA with well-tolerated oral bedaquiline (BDQ) and a shortened 9-12 month regimen.DESIGN: Using a Markov model, we analyzed the 5-year budgetary impact and cost per successful treatment outcome of four regimens: 1) IA long-course, 2) oral long-course, 3) IA short-course, and 4) oral short-course. We used the South African MDR/RR-TB case register (2013-2015) to assess treatment outcomes for the then-standard IA long-course. Data on the improvement in outcomes for BDQ-based regimens were based on the literature. Costs were estimated from the provider perspective using costs incurred to provide decentralized treatment for MDR-TB at a Johannesburg hospital.RESULTS: Based on our analysis, by 2023, the cost/successful outcome for the four regimens was respectively 1) US$7374, 2) US$7860, 3) US$5149, and 4) US$4922. The annual total cost of each regimen was US$37 million, US$43 million, US$26 million, and US$28 million.CONCLUSION: Despite the high cost of BDQ, a BDQ-based shortened regimen for the treatment of MDR/RR-TB will result in improved treatment outcomes and cost savings for South Africa.

Fasting plasma glucose and risk factor assessment: Comparing sensitivity and specificity in identifying gestational diabetes in urban black African women.

BACKGROUND: Identifying women with gestational diabetes mellitus (GDM) allows interventions to improve perinatal outcomes. A fasting plasma glucose (FPG) level ≥5.1 mmol/L is 100% specific for a diagnosis of GDM. The International Association of Diabetes and Pregnancy Study Groups acknowledges that FPG <4.5 mmol/L is associated with a low probability of GDM. OBJECTIVES: The validity of selective screening based on the presence of risk factors was compared with the universal application of FPG ≥4.5 mmol/L to identify women with GDM. FPG ≥4.5 mmol/L or the presence of one or more risk factors was assumed to indicate an intermediate to high risk of GDM and therefore the need for an oral glucose tolerance test (OGTT). METHODS: Consecutive black South African (SA) women were recruited to a 2-hour 75 g OGTT at 24 - 28 weeks' gestation in an urban community health clinic. Of 969 women recruited, 666 underwent an OGTT, and of these 589 were eligible for analysis. The glucose oxidase laboratory method was used to measure plasma glucose concentrations. The World Health Organization GDM diagnostic criteria were applied. All participants underwent a risk factor assessment. The χ2 test was used to determine associations between risk factors and a positive diagnosis of GDM. The sensitivity and specificity of a positive diagnosis of GDM were calculated for FPG ≥4.5 mmol/L, FPG ≥5.1 mmol/L, and the presence of one or more risk factors. RESULTS: The prevalence of overt diabetes mellitus and GDM was 0.5% and 7.0%, respectively. Risk factor-based selective screening indicated that 204/589 (34.6%) of participants needed an OGTT, but 18/41 (43.9%) of positive GDM diagnoses were missed. Universal screening using the FPG threshold of ≥4.5 mmol/L indicated that 152/589 (25.8%) of participants needed an OGTT, and 1/41 (2.4%) of positive diagnoses were missed. An FPG of ≥5.1 mmol/L identified 36/41 (87.8%) of GDM-positive participants. The sensitivity and specificity of the presence of one or more risk factors were 56% and 67%, respectively. The sensitivity and specificity of FPG ≥4.5 mmol/L were 98% and 80%, respectively. CONCLUSIONS: Universal screening using FPG ≥4.5 mmol/L had greater sensitivity and specificity in identifying GDM-affected women and required fewer women to undergo a resource-intensive diagnostic OGTT than risk factor-based selective screening. A universal screening strategy using FPG ≥4.5 mmol/L may be more efficient and cost-effective than risk factor-based selective screening for GDM in black SA women.

The response of weaned piglets to dietary valine and leucine.

Valine (Val) is considered to be the fifth-limiting amino acid in a maize-soyabean meal diet for pigs. Excess leucine (Leu) levels often occur in commercial diets, which may attenuate the effect of Val deficiency because of an increased oxidation of Val. The objective of the present experiment was to determine the effect of increasing concentrations of Leu on the response of young piglets to dietary Val. In all, 75 Large White×Landrace entire male pigs, 44 days of age and with a mean starting weight of 13.5 kg, were used. Three of these were sacrificed at the start to determine their mean initial chemical composition. A summit feed first limiting in Val was serially diluted with a non-protein diluent to produce a series of five digestible Val concentrations of 11.9, 10.1, 8.3, 6.6 and 4.8 g/kg, with a sixth treatment being added to test that the feeds were limiting in Val. Three identical Val series, each with six levels of Val, were supplemented with increasing amounts of Leu (23, 45 and 67 g/kg), thus 18 treatments in total. All pigs were killed at the end of the trial after 18 days for analysis of water, protein, lipid and ash in the carcass. The levels of Val and Leu and their interaction significantly influenced all the measurements taken in the trial. Daily gain in liveweight, water and protein, and feed conversion efficiency all increased with dietary Val content, whereas feed intake decreased as both Val and Leu contents increased. The deleterious effect of increased Leu on feed intake and growth was more marked at lower levels of Val. Supplementing the feed with the lowest Val content with additional Val largely overcame the effect of excess Leu. The efficiency of utilisation of Val for protein growth was unaffected by the level of Leu in the feed, the primary response to excess Leu being a reduction in feed intake. An intake of around 9 g Val/day yielded maximal protein growth during the period from 44 to 62 days of age in pigs of the genotype used in this trial.

Investigation of isoniazid and ethionamide cross-resistance by whole genome sequencing and association with poor treatment outcomes of multidrug-resistant tuberculosis patients in South Africa.

OBJECTIVE/BACKGROUND: Ethionamide (ETH) and isoniazid (INH) are part of the backbone regimen used for the treatment of multidrug-resistant tuberculosis (MDR-TB). Both ETH and INH are structurally similar and are activated by ethA and katG gene products. Resistance to INH among MDR-TB patients may cause ETH to be ineffective, as both target nicotinamide adenine dinucleotide-dependent enoyl-acyl carrier protein reductase inhA protein and mutations within inhA gene may lead to their cross-resistance. Furthermore, ETH resistance is caused by mutations within ethA and ethR genes forming part of the ETH drug activation pathway. Nicotinamide adenine dinucleotide is coded by the ndh gene, and its overexpresion may lead cross-resistance between INH and ETH drugs. Phenotypic drug susceptibility testing of ETH is difficult and often unreliable. We used whole genome sequencing to compare inhA, inhA promoter, ethA, ethR ndh, and katG genetic regions in serial isolates (baseline and follow-up) with treatment outcomes. METHODS: MDR-TB strains were collected from 46 patients before and during second-line drug treatment in KwaZulu-Natal and Eastern Cape between 2005 and 2009. All patients had phenotypically determined MDR-TB at baseline and had treatment outcomes documented. Unfavorable treatment outcomes were defined as death, default, and failure, while favorable outcomes were cure and treatment completion. Each strain had baseline and at least one strain collected on follow-up. From each strain, DNA was extracted from colonies grown on Löwenstein-Jensen slants, and fragment and jumping paired-end Illumina DNA libraries were constructed and sequenced on the Illumina HiSeq 2000 (Broad Institute, Cambridge, MA, USA). Sequences were aligned to H37Rv genome and Pilon was run to generate a list of SNPs. In silico spoligotyping was performed to a database 43 unique spacer sequences. Cross-resistance was defined as the presence of both inhA and either ethA or ethR mutations in clinical isolates. RESULTS: A total of 92 sequences from 46 serial isolates of MDR-TB patients from KwaZulu-Natal (29 isolates) and Eastern Cape (17 isolates) were analyzed. Most patients (29/46; 63.0%) had unfavorable outcomes, 13 (28.3%) had favorable outcomes, while four (8.7%) had unknown outcomes. Phylogenetic reconstruction revealed that primary genotype differed by province. The Beijing genotype was predominant in Eastern Cape, while EuroAmerican lineage (S, T, LAM, X) was found in KwaZulu-Natal. Whole genome analysis revealed nonsynonymous insertions and deletions within katG, ethA, ethR, ndh, and inhA and its promoter region. Among patients with treatment outcome data, mutations were detected in 92.8% in katG, 50% in inhA, 53.6% in ethA, 2.4% in ethR, and 19% in ndh. The majority of mutations causing ETH (20/29; 68.9%) and INH (18/29; 62.1%) resistance occurred among patients with unfavorable outcomes. Both inhA and either ethA or ethR mutations were detected in 16/29 (55.2%) patients with unfavorable outcomes. Cross-resistance of both INH and ETH drugs was associated with unfavorable treatment outcomes (p=0.021) in 16/29 (55.2%) patients compared with favorable treatment outcomes in 2/13 (15.4%) patients. CONCLUSION: Baseline ETH molecular resistance before second-line treatment is a concern. Unfavorable treatment outcomes of patients with ethA, ethR, and inhA mutations highlight the importance of genotypic testing before initiation of treatment containing ETH. The clinical significance of whole genome analysis for early detection of mutations predictive of treatment failure needs further investigation.

A comparison of the leaf gel extracts of Aloe ferox and Aloe vera in the topical treatment of atopic dermatitis in Balb/c mice.

Aloe vera gel is widely used in the treatment of an array of disturbances, especially skin disorders. The wound-healing effects have been attributed to its moisturizing and anti-inflammatory effects as well as its beneficial effect on the maturation of collagen. The aim of the present study is to compare the effects of topically applied extracts of Aloe ferox with that of Aloe vera on the symptoms as well as IgE levels of a mouse model of atopic dermatitis (AD). Mice were sensitized and challenged with 2,4-dinitrochlorobenzene and treated afterwards for 10 consecutive days with the gels of either A. ferox or A. vera applied topically to the affected areas. A placebo gel was used for the control mice. Blood was collected at the beginning and end of the treatment period to measure serum IgE levels. Although the gels of both the Aloe species inhibited the cutaneous inflammatory response as well as serum IgE levels in the rats, the extracts of A. ferox were superior to that of A. vera in reducing IgE levels. The gels of A. ferox and A. vera, applied topically, may be a safe and useful alternative to antihistamines and topical corticosteroids, for the treatment of patients suffering from recurring chronic AD.

Antiviral efficacy of entecavir in nucleos(t)ide-naïve patients of Black/African descent with chronic hepatitis B.

This single-arm, open-label, descriptive study assessed the efficacy and safety of entecavir (ETV) in nucleos(t)ide-naïve Black/African American patients with chronic hepatitis B (CHB), a patient population underrepresented in ETV registration trials. Forty patients with HBeAg(+) or HBeAg(-) compensated CHB of self-described Black/African American race received ETV 0.5 mg daily for 52 weeks; 37 patients completed 52 weeks of treatment. At Week 48, 29/40 (72.5%, noncompleter = failure) patients achieved the primary endpoint of HBV DNA <50 IU/mL. Rates for HBeAg loss (11/22; 50%) and HBeAg seroconversion (9/22; 41%) were high, possibly due to the high HBV genotype A prevalence (70%). No patient experienced virological breakthrough. Samples for resistance testing were available in 6/8 patients with HBV DNA >50 IU/mL at Week 48 or last on-treatment visit. No ETV resistance was detected. The safety profile of ETV was consistent with that observed in ETV registration trials. This study shows that in Black/African American patients with CHB, ETV was well tolerated and demonstrated comparable antiviral efficacy to that observed in White and Asian patients in ETV Phase III studies.

RET promoter variations in familial African degenerative leiomyopathy (ADL): first report of a possible genetic-environmental interaction.

African degenerative leiomyopathy (ADL, DL, Bantu pseudo-Hirschsprung's disease) is a distinctive visceral myopathy, of unknown etiology, occurring in Africa. It has a classical clinical and histologic picture in young indigenous African children. It presents as intestinal pseudo-obstruction with a massive megacolon due to degeneration of smooth muscle without aganglionosis. Because of its late presentation and geographical and ethnic distribution, it is thought to be an acquired degenerative hollow visceral myopathy. Only one previous report of familial recurrence exists. The main Hirschsprung susceptibility gene RET is a potential candidate gene in this condition, because of its role in the development of the intrinsic innervation and ganglia of the smooth muscle layers of the gastro-intestinal tract. We report a second case of familial ADL recurrence and explore possible etiologic causes including variations of the RET gene. Multiple variations in the RET promoter were identified in this case which leads to the possibility of a genetic-environmental predisposition for this condition. We therefore hypothesize that RET may play a modulating role in ADL susceptibility (and possibly other visceral myopathies). It is possible that subtle malformations in the ENS may result from RET dysfunction which then predisposes the individual to environmental influences which initiate the later onset of muscle degeneration.

Randomised clinical trial: sustained response to PPI treatment of symptoms resembling functional dyspepsia and irritable bowel syndrome in patients suffering from an overlap with erosive gastro-oesophageal reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease (GERD), functional dyspepsia (FD) and irritable bowel syndrome (IBS) are highly prevalent gastrointestinal conditions with accumulating evidence of overlap in patients. Despite availability of a vast body of research related to individual disorders, major pharmacological breakthrough in treatment of the overlap condition is still lacking. AIM: To assess sustainability of GERD healing and whether known beneficial effects of proton pump inhibitor treatment on GERD also extend to symptoms suggestive of FD and IBS. METHODS: A total of 626 patients with reflux oesophagitis were treated with pantoprazole for up to 16 weeks depending on healing of GERD, followed by an observational phase of up to 6 months without treatment. Rates of patients suffering from GERD, FD or IBS were assessed at baseline, and at last visits of treatment and observational phase. RESULTS: Rates of patients with reflux oesophagitis and concomitantly with reflux symptoms, FD or IBS were each significantly lower after pantoprazole treatment (P < 0.0001). While rates of patients with reflux signs or symptoms increased again during observational phase, rates of FD and IBS were maintained at the low level after cessation of medication (P < 0.0001). CONCLUSIONS: Pantoprazole is efficacious in the treatment of patients suffering from signs and symptoms suggesting an overlap of GERD, FD and/or IBS, providing a sustained response post-treatment in FD and IBS symptom categories. Mechanisms underlying the beneficial effects of improvement in reflux oesophagitis on symptoms suggestive of FD or IBS still need to be determined.

Improvement of non-steroidal anti-inflammatory drug-induced gastrointestinal symptoms during proton pump inhibitor treatment: are G-protein ß3 subunit genotype, Helicobacter pylori status, and environmental factors response modifiers?

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with significant upper and lower gastrointestinal (GI) morbidity. AIM: To determine the efficacy and safety of pantoprazole versus placebo in controlling GI symptoms during treatment with NSAIDs and to evaluate the influence of potential response modifiers. METHODS: 800 patients with GI complaints during NSAID treatment were randomized to pantoprazole 20 mg once daily or placebo for 4 weeks in this double-blind, multicenter trial. Assessments included the difference in cumulated overall symptom load of any GI complaint during treatment (primary endpoint), proportion of days without GI symptoms, and influence of risk factors such as gender, age, alcohol consumption, smoking, Helicobacter pylori status, and GNB3 genotype SNP rs5443 (825C>T) on symptom load. RESULTS: At 4 weeks, cumulated overall symptom load was significantly lower in pantoprazole than placebo recipients [p < 0.0001; intent-to-treat (ITT)]; the effect was statistically significant after 7 days' treatment. Pantoprazole versus placebo recipients had 54 versus 29% of days without GI symptoms (p < 0.0001; ITT). Neither common risk factors nor GNB3 genotype were significantly associated with therapeutic response, while GNB3 825TT versus CT was associated with a significantly higher baseline symptom load (p < 0.05). CONCLUSION: In the population studied, treatment with the proton pump inhibitor pantoprazole significantly improves GI symptoms during NSAID therapy, irrespective of the risk factors investigated or GNB3 genotype.

Non-alcoholic fatty liver disease (NAFLD) in the Western Cape: a descriptive analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in Western countries, but the disease profile has not yet been described in South Africa. NAFLD affects all spheres of society, especially the poorest and least educated. Aim. To investigate the demographics and clinical and biochemical features of South African patients diagnosed with non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH) in the Western Cape, South Africa. DESIGN/METHOD: Overweight/obese subjects were screened by ultrasound and those with fatty liver/hepatomegaly were included. Liver biochemistry, insulin resistance (using the insulin resistance homeostasis model assessment method for insulin resistance, HOMA-IR) and body mass index were assessed and liver biopsies were performed on patients older than 45 years with persistently abnormal liver function and/or hepatomegaly. RESULTS: We screened 233 patients: 69% coloured, 25% Caucasian, 5% black and 1% Asian. The majority (73%) were female. NAFLD was confirmed histologically in 111 patients, of whom 36% had NASH and 17% advanced liver fibrosis. No black patient had advanced fibrosis. Subjects with NASH had higher mean triglyceride (p=0.03) and cholesterol (p=0.01) levels than subjects with NAFL. All patients were insulin resistant/diabetic. HOMA-IR and not the degree of obesity was strongly associated with advanced fibrosis (p=0.09). CONCLUSION: This study is the first to describe the clinical characteristics of NAFLD in South Africa, albeit only in the Western Cape population. Insulin resistance was the universal factor present. The degree of obesity was not associated with severity of disease. The role of genetic risk factors in disease development and severity remains to be defined.

DDT residues in water, sediment, domestic and indigenous biota from a currently DDT-sprayed area.

DDT is used for indoor residual spraying (IRS) in Limpopo Province, northern South Africa to control malaria. Through IRS, DDT may reach the outdoor environment via dust and air and from possible spillages during application. In this area the local people consume domestic chickens, wild fish or birds. Fish from the river catchment and impoundments seem to be the major source of protein intake. Water, sediment and tissue samples from two such fish species, domestic chickens and wild birds (terrestrial and aquatic) from this DDT-sprayed area were analysed for DDT and metabolite residues. The samples contained p,p'-DDT, p,p'-DDD and p,p'-DDE residues, with the latter the most ubiquitous and in the highest concentrations. These findings raise concern that both water and food may be major routes of human exposure to DDT and metabolites, thereby posing possible adverse human health implications to the local communities.

The anti-tumour properties and biodistribution (as determined by the radiolabeled equivalent) of Au-compounds intended as potential chemotherapeutics.

The anti-tumour activity of the Au (I) phosphine complex [Au(dppe(2)]Cl was first discovered in the mid 1980s although promising results were obtained it did not pass clinical studies because of its toxicity to organs such as the liver and heart. The aim of this study was to determine whether the two novel gold compounds (MM5 and MM6), selected for this study, have higher selectivity for cancer cells with less toxicity towards normal cells than [Au(dppe)(2)]Cl, and also to determine whether they have improved bio distribution compared to [Au(dppe)(2)]Cl. The Au-compounds as potential chemotherapeutic drugs were evaluated by using radioactive tracers in the in vitro and in vivo studies. Results obtained from these experiments showed that the uptake of these experimental compounds was dependent on their octanol/water partition coefficient. However; the inhibition of cell growth did not correlate with the uptake of these compounds by the cells that were tested. In terms of the total uptake it was found that the compounds that were less lipophilic (MM5, MM6) were taken up less efficiently in cells than those that are more lipophilic. Therefore hydrophilic drugs are expected to have a limited biodistribution compared to lipophilic drugs. This might imply a more selective tumour uptake.

Clinical trial: intravenous pantoprazole vs. ranitidine for the prevention of peptic ulcer rebleeding: a multicentre, multinational, randomized trial.

BACKGROUND: Controlled pantoprazole data in peptic ulcer bleeding are few. AIM: To compare intravenous (IV) pantoprazole with IV ranitidine for bleeding ulcers. METHODS: After endoscopic haemostasis, 1256 patients were randomized to pantoprazole 80 mg+8 mg/h or ranitidine 50 mg+13 mg/h, both for 72 h. Patients underwent second-look endoscopy on day 3 or earlier, if clinically indicated. The primary endpoint was an overall outcome ordinal score: no rebleeding, rebleeding without/with subsequent haemostasis, surgery and mortality. The latter three events were also assessed separately and together. RESULTS: There were no between-group differences in overall outcome scores (pantoprazole vs. ranitidine: S0: 91.2 vs. 89.3%, S1: 1.5 vs. 2.5%, S2: 5.4 vs. 5.7%, S3: 1.7 vs. 2.1%, S4: 0.19 vs. 0.38%, P = 0.083), 72-h clinically detected rebleeding (2.9% [95% CI 1.7, 4.6] vs. 3.2% [95% CI 2.0, 4.9]), surgery (1.9% [95% CI 1.0, 3.4] vs. 2.1% [95% CI 1.1, 3.5]) or day-3 mortality (0.2% [95% CI 0, 0.09] vs. 0.3% [95% CI 0, 1.1]). Pantoprazole significantly decreased cumulative frequencies of events comprising the ordinal score in spurting lesions (13.9% [95% CI 6.6, 24.7] vs. 33.9% [95% CI 22.1, 47.4]; P = 0.01) and gastric ulcers (6.7% [95% CI 4, 10.4] vs. 14.3% [95% CI 10.3, 19.2], P = 0.006). CONCLUSIONS: Outcomes amongst pantoprazole and ranitidine-treated patients were similar; pantoprazole provided benefits in patients with arterial spurting and gastric ulcers.

Brown coal derived humate inhibits contact hypersensitivity; an efficacy, toxicity and teratogenicity study in rats.

OBJECTIVES: The effects of two humate products were compared to that of prednisolone on a contact hypersensitivity rat model. METHODS: Rats, sensitized with dinitrofluorobenzene (DNFB), were placed on a daily oral treatment of 61 mg/kg BW of humate derived from either leonardite or bituminous coal or on prednisolone at one mg/kg BW and challenged 6 days later with a topical application of DNFB to the right ear. The inflamed ears were measured daily. In a toxicity study rats were exposed to daily oral treatment of leonardite humate at 1,000 mg/kg BW for 1 month. A teratogenicity study was done where pregnant rats were treated with 500 mg/kg BW on days 5 to 17 of pregnancy. RESULTS: Only the leonardite humate compared favourably with prednisolone in suppressing contact hypersensitivity. No signs of toxicity were observed and weight gain was normal during the 6-day and 1 month treatments and during the teratogenicity study with the leonardite humate. However, the rats on the other two products experienced slower weight gain. CONCLUSION: The identification of a naturally occurring nontoxic compound with anti-inflammatory activity is exciting and merits further evaluation in the treatment of patients suffering from inflammatory conditions.