Strategies to Accelerate HIV Care and Antiretroviral Therapy Initiation After HIV Diagnosis: A Randomized Trial.

: Determine the effectiveness of strategies to increase linkage to care after testing HIV positive at mobile HIV testing in South Africa. : Unmasked randomized controlled trial. : Recruitment of adults testing HIV positive and not currently in HIV care occurred at 7 mobile HIV counseling and testing units in urban, periurban, and rural South Africa with those consenting randomized 1:1:1:1 into 1 of 4 arms. Three strategies were compared with standard of care (SOC): point-of-care CD4 count testing (POC CD4), POC CD4 plus longitudinal strengths-based counseling (care facilitation; CF), and POC CD4 plus transport reimbursement (transport). Participants were followed up telephonically and through clinic records and analyzed with an intention-to-treat analysis. : From March 2013 to October 2014, 2558 participants were enrolled, of whom 160 were excluded postrandomization. Compared with the SOC arm where 298 (50%) reported having entered care, linkage to care was 319 (52%) for POC CD4, hazard ratio (HR) 1.0 [95% confidence interval (CI): 0.89 to 1.2, P = 0.6]; 331 (55%) for CF, HR: 1.1 (95% CI: 0.84 to 1.3, P = 0.2); and 291 (49%) for transport, HR 0.97 (95% CI: 0.83 to 1.1, P = 0.7). Linkage to care verified with clinical records that occurred for 172 (29%) in the SOC arm; 187 (31%) in the POC CD4 arm, HR: 1.0 (95% CI: 0.86 to 1.3, P = 0.6); 225 (38%) in the CF arm, HR: 1.4 (95% CI: 1.1 to 1.7, P = 0.001); and 180 (31%) in the transport arm, HR: 1.1 (95% CI: 0.88 to 1.3, P = 0.5). : CF improved verified linkage to care from 29% to 38%.<br/

Leave entitlements, time off work and the household financial impacts of quarantine compliance during an H1N1 outbreak

The Australian state of Victoria, with 5.2 million residents, enforced home quarantine during a H1N1 pandemic in 2009. The strategy was targeted at school children. The objective of this study was to investigate the extent to which parents’ access to paid sick leave or paid carer’s leave was associated with (a) time taken off work to care for quarantined children, (b) household finances, and (c) compliance with quarantine recommendations.This project was funded by two NHMRC Strategic Awards: “Call for research on H1N1 influenza 09 to inform public policy” (#628962) and “Changing patterns of work: Impacts on physical and mental health and the mediating role of resilience and social capital” (#375196). JM is supported by a NHMRC Career Development Award; DS is funded by an ARC Federation Fellowship

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

TB Fast Track: a study to evaluate the effect of a point-of-care TB test-and-treat algorithm on early mortality in people with HIV accessing ART, a trial with randomisation at clinic level

Background Early mortality for HIV-positive people starting antiretroviral therapy (ART) remains high in resource-limited settings, with tuberculosis the most important cause. Existing rapid diagnostic tests for tuberculosis lack sensitivity among HIV-positive people, and consequently, tuberculosis treatment is either delayed or started empirically (without bacteriological confirmation). We developed a management algorithm for ambulatory HIV-positive people, based on body mass index and point-of-care tests for haemoglobin and urine lipoarabinomannan (LAM), to identify those at high risk of tuberculosis and mortality. We designed a clinical trial to test whether implementation of this algorithm reduces six-month mortality among HIV-positive people with advanced immunosuppression. Methods/design The TB Fast Track study is an open, pragmatic, cluster randomised superiority trial, with 24 primary health clinics randomised to implement the intervention or standard of care. Adults (aged ≥18 years) with a CD4 count of 150 cells/μL or less, who have not received any tuberculosis treatment in the last three months, or ART in the last six months, are eligible. In intervention clinics, the study algorithm is used to classify individuals as at high, medium or low probability of tuberculosis. Those classified as high probability start tuberculosis treatment immediately, followed by ART after two weeks. Medium-probability patients follow the South African guidelines for test-negative tuberculosis and are reviewed within a week, to be re-categorised as low or high probability. Low-probability patients start ART as soon as possible. The primary outcome is all-cause mortality at six months. Secondary outcomes include severe morbidity, time to ART start and cost-effectiveness. Discussion This trial will test whether a primary care-friendly management algorithm will enable nurses to identify HIV-positive patients at the highest risk of tuberculosis, to facilitate prompt treatment and reduce early mortality. There remains an urgent need for better diagnostic tests for tuberculosis, especially for people with advanced HIV disease, which may render empirical treatment unnecessary. Trial registration This trial was registered with Current Controlled Trials (identifier: ISRCTN35344604) on 12 September 2012

Tuberculosis Prevention in South Africa

Background South Africa has one of the highest per capita rates of tuberculosis (TB) incidence in the world. In 2012, the South African government produced a National Strategic Plan (NSP) to control the spread of TB with the ambitious aim of zero new TB infections and deaths by 2032, and a halving of the 2012 rates by 2016. Methods We used a transmission model to investigate whether the NSP targets could be reached if immediate scale up of control methods had happened in 2014. We explored the potential impact of four intervention portfolios; 1) “NSP” represents the NSP strategy, 2) “WHO” investigates increasing antiretroviral therapy eligibility, 3) “Novel Strategies” considers new isoniazid preventive therapy strategies and HIV “Universal Test and Treat” and 4) “Optimised” contains the most effective interventions. Findings We find that even with this scale-up, the NSP targets are unlikely to be achieved. The portfolio that achieved the greatest impact was “Optimised”, followed closely by “NSP”. The “WHO” and “Novel Strategies” had little impact on TB incidence by 2050. Of the individual interventions explored, the most effective were active case finding and reductions in pre-treatment loss to follow up which would have a large impact on TB burden. Conclusion Use of existing control strategies has the potential to have a large impact on TB disease burden in South Africa. However, our results suggest that the South African TB targets are unlikely to be reached without new technologies. Despite this, TB incidence could be dramatically reduced by finding and starting more TB cases on treatment

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2–69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m−2 i.v. day 1 and gemcitabine 1000 mg m−2 i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20–46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life

Current and potential geographical distribution of Platymeris biguttatus (Linnaeus, 1767) with description of nymphs

Background: The description of Platymeris biguttatus (Linnaeus 1767) nymphal instars as well as the prediction of the potentially suitable ecological niche was the main goal of this study. Our research was based on 258 specimens of P. biguttatus species of museum collections. A set of 23 environmental predictor variables covering Africa was used at ecological niche modeling - a method performed using the Maxent software to prepare potential distribution maps for this species. Results: The results suggested the most suitable areas seen as potentially suitable ecological niche for P. biguttatus in Africa. A jackknife test showed that temperature seasonality and percentage of tree cover were among the most important environmental variables affecting the distribution of the species. The analysis of climate preferences shows that most of the potentially suitable niches for this species were located in the area of tropical savanna climate, with a small participation of tree vegetation. Conclusions: P. biguttatus was only known to be widely distributed in the tropical part of continental Africa. Thanks to the ecological niche modeling methods and the museum data on the occurrence of the species, we introduced new information about potentially suitable ecological niches and the possible range of distribution

What causes symptoms suggestive of tuberculosis in HIV-positive people with negative initial investigations?

OBJECTIVE: To identify the causes of symptoms suggestive of tuberculosis (TB) among people living with the human immunodeficiency virus (PLHIV) in South Africa. METHODS: A consecutive sample of HIV clinic attendees with symptoms suggestive of TB (1 of cough, weight loss, fever or night sweats) at enrolment and at 3 months, and negative initial TB investigations, were systematically evaluated with standard protocols and diagnoses assigned using standard criteria. TB was 'confirmed' if Mycobacterium tuberculosis was identified within 6 months of enrolment, and 'clinical' if treatment started without microbiological confirmation. RESULTS: Among 103 participants, 50/103 were pre-antiretroviral therapy (ART) and 53/103 were on ART; respectively 68% vs. 79% were female; the median age was 35 vs. 45 years; the median CD4 count was 311 vs. 508 cells/mm³. Seventy-two (70%) had 5% measured weight loss and 50 (49%) had cough. The most common final diagnoses were weight loss due to severe food insecurity (n = 20, 19%), TB (n = 14, 14%: confirmed n = 7; clinical n = 7), other respiratory tract infection (n = 14, 14%) and post-TB lung disease (n = 9, 9%). The basis for TB diagnosis was imaging (n = 7), bacteriological confirmation from sputum (n = 4), histology, lumbar puncture and other (n = 1 each). CONCLUSION: PLHIV with persistent TB symptoms require further evaluation for TB using all available modalities, and for food insecurity in those with weight loss

Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer

<p>Abstract</p> <p>Background</p> <p>Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs.</p> <p>Methods</p> <p>To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected.</p> <p>Results</p> <p>For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN.</p> <p>Conclusions</p> <p>Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.</p