Prevalence and Characteristics of HIV-Associated Stroke in a Tertiary Hospital Setting in South Africa.

BACKGROUND AND OBJECTIVES: Antiretroviral treatment (ART) era HIV-associated stroke data from sub-Saharan Africa are limited. We determined the prevalence of HIV in patients presenting with acute symptomatic stroke and compared risk factors, clinical characteristics, and brain imaging with age-matched stroke patients without HIV. METHODS: We conducted a retrospective study of adults presenting with any type of stroke to Tygerberg Hospital in a 12-month period. Patients living with HIV (PLWH) and HIV-uninfected (HIV-) patients were matched based on age group (1:2 ratio). Patients were identified by keyword search, while HIV status was ascertained from laboratory data. Clinical and imaging data were extracted from medical records. RESULTS: Among 884 patients presenting with acute strokes, the minimum prevalence of HIV infection was 9.3% (95% CI: 7.4%-11.2%), with 496 patients (56.1%) with negative HIV status and 306 patients with unknown HIV status (34.6%). The mean age at presentation in PLWH was 46 (±11) years compared with 55 (±14) years in HIV- patients (p < 0.001). Smoking was less prevalent in PLWH with an adjusted relative risk ratio of RR = 0.58 (95% CI: 0.39-0.86). Concurrent infection was more prevalent in PLWH (25.6% vs 4.9%, p ≤ 0.001) with an adjusted relative risk ratio of RR = 2.07 (95% CI: 1.49-2.84), largely in patients with a CD4 count <200 cells/µL. PLWH with higher CD4 counts (≥200 cells/µL, 51.3%) had more traditional risk factors and less concurrent infection. Among PLWH, 68.3% were on ART, and 39.3% of them had been started or restarted on ART within the past 6 months. Basal ganglia infarcts (35.6% vs 18.3%, p = 0.014) and multiple vascular territory involvement (25.4% vs 7.7%, p = 0.002) were more common in PLWH. Clinical presentation, ischemic stroke type, and in-hospital outcomes did not differ between the groups. DISCUSSION: Stroke patients with HIV were younger, had less traditional cardiovascular risk factors, and more concurrent infections than patients without HIV, especially those with a lower CD4 count. Recent ART initiation or reinitiation rates were high. Significant differences in CT brain imaging findings were seen. Understanding the multifactorial mechanisms underlying increased stroke risk, including associated infections and potential ART-associated immune reconstitution, is crucial and needs further study.

HIV infection and anaemia do not affect HbA1c for the detection of diabetes in black South Africans: Evidence from the Durban Diabetes Study.

OBJECTIVE: South Africa has a high burden of HIV infection and anaemia. These conditions may cause HbA1c to over- or underestimate glycaemia; however, this has not been comprehensively investigated in African populations. We assessed the association of anaemia, HIV infection and antiretroviral therapy (ART) with HbA1c , and implications for the detection and diagnosis of diabetes, in a black South African population. RESEARCH DESIGN AND METHODS: In this population-based cross-sectional study in eThekwini municipality (Durban), South Africa, we assessed HbA1c and conducted oral glucose tolerance tests (OGTTs), HIV diagnostic tests and full blood count measurements among 1067 participants without a history of diabetes diagnosis. Linear regression was used to examine differences in HbA1c by anaemia (comparator: no anaemia), or HIV and ART (comparator: no HIV) status. HbA1c -based diabetes prevalence was compared with OGTT-based prevalence among individuals with anaemia and with untreated and ART-treated HIV. RESULTS: In adjusted analyses, normocytic and microcytic anaemia were associated with higher HbA1c compared with no anaemia, whereas macrocytic anaemia and ART-treated HIV were associated with lower HbA1c compared with no anaemia and no HIV, respectively. However, magnitudes of association were small (range: ß  = -3.4 mmol/mol or -0.31%, p < 0.001 [macrocytic anaemia] to ß = 2.1 mmol/mol or 0.19%, p < 0.001 [microcytic anaemia]). There was no significant difference in diabetes prevalence based on HbA1c or OGTT among individuals with anaemia (2.9% vs. 3.3%, p = 0.69), untreated HIV (1.6% vs. 1.6% p = 1.00) or ART-treated HIV (2.9% vs. 1.2%, p = 0.08). CONCLUSIONS: Our results suggest that anaemia and HIV status appear unlikely to materially affect the utility of HbA1c for diabetes detection and diagnosis in this population. Further studies are needed to examine these associations in sub-Saharan African populations.

Age at diagnosis as a prognostic factor in South African children with neuroblastoma.

PURPOSE: Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point. METHODS: Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests. RESULTS: The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis. CONCLUSION: The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa.

Incident tuberculosis disease in patients receiving biologic therapies in the Western Cape, South Africa from 2007 to 2018.

BACKGROUND: South Africa has one of the highest tuberculosis incidence rates. Biologic disease-modifying anti-rheumatic drugs are associated with an increased risk of tuberculosis. The objective of this study was to describe the tuberculosis disease incidence rate among public sector patients receiving biologic therapies in the Western Cape Province. METHODS: A retrospective, descriptive analysis was undertaken using routine health data collated by the Provincial Health Data Centre from January 2007 (first use of biologic therapy in the Western Cape) to September 2018. RESULTS: We identified 609 patients treated with tumour necrosis factor-alpha (TNF-α) or non-TNF-α biologic therapies. Thirty-seven (37) patients developed tuberculosis after biologic therapy exposure, of whom the majority (78%) had an immune mediated inflammatory disease and the remainder (22%) a haematologic malignancy. The incidence rate of tuberculosis per 100,000 person-years was 2227 overall [95% confidence interval (CI): 1591, 3037]. Patients treated with TNF-α inhibitors and non-TNF-α inhibitors had estimated incidence rates of 2819 [95% CI: 1669, 4480] and 1825 [95% CI: 1131, 2797], respectively (p = 0.10). CONCLUSION: Patients exposed to both TNF-α and non-TNF-α biologic therapies may have a higher incidence of tuberculosis disease compared to the background risk of 681 cases per 100,000 per year in the Western Cape.

The Etiology of Intraocular Inflammation in HIV Positive and HIV Negative Adults at a Tertiary Hospital in Cape Town, South Africa.

PURPOSE: To describe the patterns of uveitis in South Africa. METHODS: Prospective cross-sectional study. RESULTS: One hundred and six patients were enrolled and 37.7% had human immune-deficiency virus (HIV) infection. Anterior and panuveitis occurred most frequently. Infectious, non-infectious and idiopathic uveitis were diagnosed in 66.0%, 17.0% and 17.0% of all cases, respectively. Eighty percent of HIV+ cases had infectious uveitis. Overall, intraocular tuberculosis (IOTB), herpetic and syphilitic uveitis were the commonest infectious causes. Sarcoidosis and HLA-B27-associated uveitis were the commonest non-infectious causes. In anterior uveitis, HIV+ cases most frequently had probable IOTB, syphilitic or idiopathic uveitis while HIV- cases had possible IOTB, idiopathic or HLA-B27-associated uveitis. In panuveitis, HIV+ cases mostly had syphilis, probable IOTB, toxoplasma and varicella-zoster virus whereas HIV- cases mostly had possible IOTB, sarcoidosis and idiopathic uveitis. CONCLUSION: Infectious uveitis is common in South Africa, especially amongst HIV+ patients. Causes of anterior and panuveitis differ between HIV+ and HIV- patients.

Polymerase Chain Reaction and Goldmann-Witmer Coefficient Testing in the Diagnosis of Infectious Uveitis in HIV-Positive and HIV-Negative Patients in South Africa.

PURPOSE: To use polymerase chain reaction (PCR) and Goldmann-Witmer coefficient (GWC) calculation to diagnose infectious uveitis. METHODS: Prospective cross-sectional study. RESULTS: Twenty-seven of 106 patients had positive PCR and/or GWC results on aqueous humor (AH) sampling and 15 of 27 (55.6%) were HIV-positive. Patients with non-anterior uveitis (NAU) were more likely to be HIV+ (p = 0.005). More than 1 possible pathogen was identified in 9 of 27 patients of whom 7 were HIV+. The final clinical diagnosis was discordant with AH findings in 9 of 27 cases. A positive EBV PCR result was associated with a discordant diagnosis (p = 0.001). All cases of herpetic anterior uveitis (42.9% HIV+) tested PCR-/GWC+ while all cases of herpetic NAU tested PCR+/GWC- (83.3% HIV+). All rubella virus cases were PCR+/GWC+. CONCLUSION: PCR is useful to diagnose herpetic NAU in HIV+ patients while GWC is useful to diagnose herpetic anterior uveitis.

Patient satisfaction and treatment adherence of stable human immunodeficiency virus-positive patients in antiretroviral adherence clubs and clinics.

BACKGROUND: South Africa has experienced a substantial increase in access to antiretroviral treatment (ART) in recent years. Effective strategies to manage access to treatment need to be incorporated into and implemented in ART programmes. Antiretroviral treatment adherence clubs are a new strategy that is being implemented in various parts of South Africa. AIM: The aim of the study was to investigate treatment adherence and patient satisfaction of stable human immunodeficiency virus (HIV) patients on ART in ART adherence clubs and clinics. SETTING: The study was conducted in the Eden district of the Western Cape, South Africa. METHODS: A cross-sectional analytical study was conducted to examine the relationships between patient satisfaction and treatment adherence in ART adherence clubs and clinics in the Eden district, Western Cape province, South Africa. Validated questionnaires were used to measure patient satisfaction and self-reported treatment adherence. RESULTS: The study included 320 participants (98 club and 222 clinic) from 13 primary health care clinics. The analyses showed that higher levels of satisfaction could be predicted with club participants compared to clinic participants (p = 0.05). There was no significant difference between clinic and club participants with regards to treatment adherence. However, being adherent was more likely in participants who were satisfied (odds ratio = 3.18, 95% confidence interval [1.14-7.11], p < 0.01). CONCLUSION: Antiretroviral treatment adherence clubs provide a service that patients are more satisfied with although they are not more adherent to treatment. This strategy may be effective for the delivery of long-term care for patients on ART.

Correction: The Influence of Second-Hand Cigarette Smoke Exposure during Childhood and Active Cigarette Smoking on Crohn's Disease Phenotype Defined by the Montreal Classification Scheme in a Western Cape Population, South Africa.

[This corrects the article DOI: 10.1371/journal.pone.0139597.].

Perioperative patient outcomes in the African Surgical Outcomes Study: a 7-day prospective observational cohort study.

BACKGROUND: There is a need to increase access to surgical treatments in African countries, but perioperative complications represent a major global health-care burden. There are few studies describing surgical outcomes in Africa. METHODS: We did a 7-day, international, prospective, observational cohort study of patients aged 18 years and older undergoing any inpatient surgery in 25 countries in Africa (the African Surgical Outcomes Study). We aimed to recruit as many hospitals as possible using a convenience sampling survey, and required data from at least ten hospitals per country (or half the surgical centres if there were fewer than ten hospitals) and data for at least 90% of eligible patients from each site. Each country selected one recruitment week between February and May, 2016. The primary outcome was in-hospital postoperative complications, assessed according to predefined criteria and graded as mild, moderate, or severe. Data were presented as median (IQR), mean (SD), or n (%), and compared using t tests. This study is registered on the South African National Health Research Database (KZ_2015RP7_22) and ClinicalTrials.gov (NCT03044899). FINDINGS: We recruited 11 422 patients (median 29 [IQR 10-70]) from 247 hospitals during the national cohort weeks. Hospitals served a median population of 810 000 people (IQR 200 000-2 000 000), with a combined number of specialist surgeons, obstetricians, and anaesthetists totalling 0·7 (0·2-1·9) per 100 000 population. Hospitals did a median of 212 (IQR 65-578) surgical procedures per 100 000 population each year. Patients were younger (mean age 38·5 years [SD 16·1]), with a lower risk profile (American Society of Anesthesiologists median score 1 [IQR 1-2]) than reported in high-income countries. 1253 (11%) patients were infected with HIV, 6504 procedures (57%) were urgent or emergent, and the most common procedure was caesarean delivery (3792 patients, 33%). Postoperative complications occurred in 1977 (18·2%, 95% CI 17·4-18·9]) of 10 885 patients. 239 (2·1%) of 11 193 patients died, 225 (94·1%) after the day of surgery. Infection was the most common complication (1156 [10·2%] of 10 970 patients), of whom 112 (9·7%) died. INTERPRETATION: Despite a low-risk profile and few postoperative complications, patients in Africa were twice as likely to die after surgery when compared with the global average for postoperative deaths. Initiatives to increase access to surgical treatments in Africa therefore should be coupled with improved surveillance for deteriorating physiology in patients who develop postoperative complications, and the resources necessary to achieve this objective. FUNDING: Medical Research Council of South Africa.

The Role of QuantiFERON®-TB Gold and Tuberculin Skin Test as Diagnostic Tests for Intraocular Tuberculosis in HIV-Positive and HIV-Negative Patients in South Africa.

PURPOSE: To compare QuantiFERON®-TB Gold and tuberculin skin testing as diagnostic tests for intraocular tuberculosis in HIV positive and negative patients. METHODS: A prospective study evaluating two different tests to help diagnose intraocular tuberculosis. RESULTS: Thirty-five of 106 patients (33.0%) were diagnosed with intraocular tuberculosis including 11 (31.4%) with HIV infection. Patients were 6.95 times more likely to have intraocular tuberculosis if TST alone was positive (p < 0.001) versus 2.19 times more likely if Quantiferon alone was positive (p = 0.04). Tuberculin skin testing showed superior specificity (60.3% vs 33.3%) (p = 0.001) but similar sensitivity (90.3% vs 85.7%), positive (54.9% vs 40.5%) and negative predictive values (92.1% vs 81.5%) compared to Quantiferon. Specificity did not increase significantly if both skin testing and Quantiferon were positive. CONCLUSIONS: In South Africa, with its high HIV burden and limited public health resources, Quantiferon testing should not replace tuberculin skin testing as it provides little additional diagnostic information.

Burkitt's Lymphoma and B-Cell Lymphoma Unclassifiable With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt's Lymphoma in Patients With HIV: Outcomes in a South African Public Hospital.

PURPOSE: Burkitt's lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (BL/DLBCL) also occurs in HIV infection. Outcomes of HIV-infected patients with BL or BL/DLBCL in a resource-constrained setting are not defined. METHODS: We performed a retrospective study of HIV-positive patients with BL or BL/DLBCL treated from 2004 to 2012 with curative intent at a publically funded academic medical center in South Africa. Differences between BL and BL/DLBCL, survival outcomes, and factors associated with survival were analyzed. RESULTS: There were 35 patients with either HIV-associated BL (24) or BL/DLBCL (11) who met study criteria. Median CD4+ T-lymphocyte count at lymphoma diagnosis was 188 cells/µL (range, 10 to 535 cells/µL). Patients with BL/DLBCL were significantly older and had less bone marrow involvement and lower baseline serum lactase dehydrogenase than patients with BL. Eighty-nine percent of patients presented with advanced disease, and 25% had baseline CNS involvement. Chemotherapy regimens consisted of cytoreduction with low-dose cyclophosphamide, vincristine, and prednisone followed by induction with vincristine, methotrexate, cyclophosphamide, doxorubicin and prednisone (LMB 86; 57%); hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine (hyper-CVAD; 20%); cyclophosphamide, doxorubicin, vincristine, and prednisone and high-dose methotrexate with leucovorin rescue on day 10 with accompanying prophylactic IT chemotherapy (Stanford regimen; 14%); and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-like; 9%) regimens. Twenty-three patients received CNS treatment or prophylaxis, and 31 received concurrent combination antiretroviral therapy. Two-year overall survival was 38% (95% CI, 22% to 54%) and 2-year event-free survival was 23% (95% CI, 11% to 38%), with no difference between histologic subtypes. Common causes of death were infection (41%) and CNS disease progression or systemic relapse (41%). CONCLUSION: Cure of HIV-associated BL and BL/DLBCL with intensive regimens is possible in resource-limited settings, but lower toxicity regimens, improved CNS prophylaxis, and increased resources for supportive care are required.

A cross-sectional, facility based study of comorbid non-communicable diseases among adults living with HIV infection in Zimbabwe.

BACKGROUND: Increased antiretroviral therapy uptake in sub-Saharan Africa has resulted in improved survival of the infected. Opportunistic infections are declining as leading causes of morbidity and mortality. Though comprehensive data are lacking, concern has been raised about the rapid emergence of non-communicable diseases (NCDs) in the African HIV care setting. We therefore set out to characterise the NCD/HIV burden among adults living and ageing with HIV infection in Zimbabwe. METHODS: We conducted a cross-sectional study among patients receiving care in a public sector facility. We reviewed patient records and determined the prevalence of comorbid and multi-morbid NCDs. Associations with patient characteristics were evaluated using univariate and multi-variate logistic regression modelling. Significance testing was done using 2-sided p values and 95 % confidence intervals calculated. RESULTS: We recruited 1033 participants. 31 % were men. Significant gender differences included: older median age, more advanced disease at baseline, and greater use of stavudine and protease inhibitor containing regimens in men compared to women. The prevalence of comorbidity and multi-morbidity were, respectively, 15.3 % (95 % CI 13.3-17.7 %) and 4.5 % (95 % CI 3.4-6.0 %). Women had higher rates than men of both co-morbidity and multi-morbid ity: 21.8 vs. 14.9 %; p = 0.010 and 5.3 vs. 2.9 %; p = 0.025 respectively. The commonly observed individual NCDs were hypertension [10.2 %; (95 % CI 8.4-12.2 %)], asthma [4.3 % (95 % CI 3.1-5.8 %)], type 2 diabetes mellitus [2.1 % (95 % CI 1.3-3.2 %)], cancer [1.8 % (95 % CI 1.1-2.8 %)], and congestive cardiac failure [1.5 % (95 % CI 0.9-2.5 %)]. After adjusting for confounding, only age categories 45-≤55 years (AOR 2.25; 95 % CI 1.37-3.69) and >55 years (AOR 5.42; 95 % CI 3.17-9.26), and female gender (AOR 2.12; 95 % CI 1.45-3.11) remained significantly and strongly associated with comorbidity risk. CONCLUSIONS: We found a substantial burden of comorbid non-communicable diseases among HIV infected patients in a high HIV and low-income setting. Integrating non-communicable diseases care, including active screening, with HIV care is recommended.

The Influence of Second-Hand Cigarette Smoke Exposure during Childhood and Active Cigarette Smoking on Crohn's Disease Phenotype Defined by the Montreal Classification Scheme in a Western Cape Population, South Africa.

BACKGROUND: Smoking may worsen the disease outcomes in patients with Crohn's disease (CD), however the effect of exposure to second-hand cigarette smoke during childhood is unclear. In South Africa, no such literature exists. The aim of this study was to investigate whether disease phenotype, at time of diagnosis of CD, was associated with exposure to second-hand cigarette during childhood and active cigarette smoking habits. METHODS: A cross sectional examination of all consecutive CD patients seen during the period September 2011-January 2013 at 2 large inflammatory bowel disease centers in the Western Cape, South Africa was performed. Data were collected via review of patient case notes, interviewer-administered questionnaire and clinical examination by the attending gastroenterologist. Disease phenotype (behavior and location) was evaluated at time of diagnosis, according to the Montreal Classification scheme. In addition, disease behavior was stratified as 'complicated' or 'uncomplicated', using predefined definitions. Passive cigarette smoke exposure was evaluated during 3 age intervals: 0-5, 6-10, and 11-18 years. RESULTS: One hundred and ninety four CD patients were identified. Cigarette smoking during the 6 months prior to, or at time of diagnosis was significantly associated with ileo-colonic (L3) disease (RRR = 3.63; 95% CI, 1.32-9.98, p = 0.012) and ileal (L1) disease (RRR = 3.54; 95% CI, 1.06-11.83, p = 0.040) compared with colonic disease. In smokers, childhood passive cigarette smoke exposure during the 0-5 years age interval was significantly associated with ileo-colonic CD location (RRR = 21.3; 95% CI, 1.16-391.55, p = 0.040). No significant association between smoking habits and disease behavior at diagnosis, whether defined by the Montreal scheme, or stratified as 'complicated' vs 'uncomplicated', was observed. CONCLUSION: Smoking habits were associated with ileo-colonic (L3) and ileal (L1) disease at time of diagnosis in a South African cohort.

Childhood cancer survival rates in two South African units.

INTRODUCTION: Childhood cancer is relatively rare, but there is a very good chance of cure. While overall survival rates of >70% are reported from developed countries, survival is much less likely in developing countries and unknown in many countries in Africa. OBJECTIVE: To analyse survival rates of childhood cancers in two South African paediatric oncology units. METHODS: This retrospective review included all children (0 - 15 years) admitted with a malignancy at two paediatric oncology units (Universitas Hospital Academic Complex in Bloemfontein, Free State, and Tygerberg Hospital in Cape Town, Western Cape) between 1987 and 2011. The protocols used in the units were similar, and all the diagnoses were confirmed histologically. RESULTS: There were 3 241 children, 53.5% of whom were males. Median follow-up was 17 months. The most common cancers were leukaemia (25.0%), brain tumours (19.5%), lymphoma (13.0%) and nephroblastoma (10.0%). The prevalences of neuroblastoma and retinoblastoma were similar at 5.8% and 5.7%, respectively. Overall survival was calculated to be 52.1%. Lymphoma and nephroblastoma had the highest survival rates at 63.9% and 62.6%, respectively. Brain tumours had the lowest survival rate at 46.4%. A comparison between ethnic groups showed white children to have the highest survival rate (62.8%); the rate for children of mixed racial origin was 53.8% and that for black children 48.5%. CONCLUSIONS: Overall survival rates for children admitted to two paediatric cancer units in South Africa were lower than data published from developed countries, because many children presented with advanced disease. New strategies to improve cancer awareness are urgently required.

Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial.

IMPORTANCE: Behavioral approaches and pharmacotherapy are of proven benefit in assisting smokers to quit, but it is unclear whether combining nicotine replacement therapy (NRT) with varenicline to improve abstinence is effective and safe. OBJECTIVE: To evaluate the efficacy and safety of combining varenicline and a nicotine patch vs varenicline alone in smoking cessation. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, placebo-controlled clinical trial with a 12-week treatment period and a further 12-week follow-up conducted in 7 centers in South Africa from April 2011 to October 2012. Four hundred forty-six generally healthy smokers were randomized (1:1); 435 were included in the efficacy and safety analyses. INTERVENTIONS: Nicotine or placebo patch treatment began 2 weeks before a target quit date (TQD) and continued for a further 12 weeks. Varenicline was begun 1 week prior to TQD, continued for a further 12 weeks, and tapered off during week 13. MAIN OUTCOMES AND MEASURES: Tobacco abstinence was established and confirmed by exhaled carbon monoxide measurements at TQD and at intervals thereafter up to 24 weeks. The primary end point was the 4-week exhaled carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 of treatment, ie, the proportion of participants able to maintain complete abstinence from smoking for the last 4 weeks of treatment, as assessed using multiple imputation analysis. Secondary end points included point prevalence abstinence at 6 months, continuous abstinence rate from weeks 9 through 24, and adverse events. Multiple imputation also was used to address loss to follow-up. RESULTS: The combination treatment was associated with a higher continuous abstinence rate at 12 weeks (55.4% vs 40.9%; odds ratio [OR], 1.85; 95% CI, 1.19-2.89; P = .007) and 24 weeks (49.0% vs 32.6%; OR, 1.98; 95% CI, 1.25-3.14; P = .004) and point prevalence abstinence rate at 6 months (65.1% vs 46.7%; OR, 2.13; 95% CI, 1.32-3.43; P = .002). In the combination treatment group, there was a numerically greater incidence of nausea, sleep disturbance, skin reactions, constipation, and depression, with only skin reactions reaching statistical significance (14.4% vs 7.8%; P = .03); the varenicline-alone group experienced more abnormal dreams and headaches. CONCLUSIONS AND RELEVANCE: Varenicline in combination with NRT was more effective than varenicline alone at achieving tobacco abstinence at 12 weeks (end of treatment) and at 6 months. Further studies are needed to assess long-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01444131.

Characteristics, management and outcome of primary hyperparathyroidism in South Africa: a single-centre experience.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterised by hypercalcaemia and elevated parathyroid hormone (PTH) levels. However, it remains a relatively underdiagnosed disease in the developing world primarily due to a lack of routine blood chemistry screening. The aim of this analysis was to evaluate the characteristics, management and outcome of patients with PHPT at a tertiary referral clinic in South Africa. METHODS: A retrospective analysis was undertaken on all patients with a diagnosis of PHPT attending the endocrinology clinic at a tertiary referral hospital in Durban, South Africa, between January 2003 and June 2009. Information on clinical presentation, past medical history, biochemistry, radiology, histology and surgical notes were recorded. Patients with multiple endocrine neoplasia were excluded. RESULTS: A total of 28 case records of PHPT were reviewed. The mean age at presentation was 60±14.5 years with a female preponderance (78.6%). The mode of presentation included referral for investigation of an abnormal serum calcium (n: 23), referral from urologist with nephrolithiasis (n: 3) and for investigation of bone disease (n: 2). Symptomatic disease was found in 26 patients (92.9%), including bone pain (75%), fatigue (46.4%) and abdominal pain (32.1%). Mean serum calcium was 3.0+0.39 (normal 2.08-2.65) mmol/L, serum intact PTH 34.7±41.5 (normal 1.2-8.5) pmol/L and serum alkaline phosphatase 206.3±340.2 (normal 53-141) mIU/L. Sestamibi scan was performed on 24 patients and an adenoma was identified in 83.3%. Of the 19 (68%) patients who had parathyroidectomy, an adenoma was identified as the cause in all cases where histology was available (n:18). Surgery was successful in 18 patients with only one patient requiring repeat parathyroidectomy for persistent hypercalcaemia. Postoperative hypocalcaemia developed in eight patients (42.1%) including four patients who required intravenous calcium infusion for symptomatic hypocalcaemia. CONCLUSIONS: PHPT is a treatable disorder with good surgical success. Asymptomatic disease was uncommon in this group of patients. This is compatible with the symptomatic pattern of presentation reported in other developing countries.

Effect of GB virus C co-infection on response to generic HAART in African patients with HIV-1 clade C infection.

In 38 African AIDS patients initiating generic HAART, GB virus C (GBV-C) RNA-positive patients retained GBV-C viraemia during 52 weeks of HAART, had a faster decline in HIV viral load (P = 0.03), fewer opportunistic infections (14.3 versus 50%, P = 0.18), and suffered no serious adverse events (none versus 61%, P = 0.008) compared with patients without GBV-C. GBV-C co-infection may be associated with a beneficial effect on African AIDS patients treated with generic HAART.

Generic antiretroviral efficacy in AIDS-associated Kaposi's sarcoma in sub-Saharan Africa.

Generic antiretroviral drugs are pivotal in the implementation of WHO's '3 by 5' programme. However, clinical experience with generics in sub-Saharan Africa is insufficiently documented. We report on 50 patients with HIV-associated Kaposi's sarcoma treated with generic fixed-dose highly active antiretroviral therapy. At 52 weeks, 74% achieved an undetectable viral load of < 50 copies/ml, 86% achieved < 400 copies/ml, and a 3.1 log10 decline from baseline. Side-effects were minimal. The outcomes support the use of generic antiretroviral therapy.