Pre-treatment mortality and loss-to-follow-up in HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients eligible for antiretroviral therapy in The Gambia, West Africa

<p>Abstract</p> <p>Background</p> <p>High early mortality rate among HIV infected patients following initiation of antiretroviral therapy (ART) in resource limited settings may indicate high pre-treatment mortality among ART-eligible patients. There is dearth of data on pre-treatment mortality in ART programmes in sub-Sahara Africa. This study aims to determine pre-treatment mortality rate and predictors of pre-treatment mortality among ART-eligible adult patients in a West Africa clinic-based cohort.</p> <p>Methods</p> <p>All HIV-infected patients aged 15 years or older eligible for ART between June 2004 and September 2009 were included in the analysis. Assessment for eligibility was based on the Gambia ART guideline. Survival following ART-eligibility was determined by Kaplan-Meier estimates and predictors of pre-treatment mortality determined by Cox proportional hazard models.</p> <p>Result</p> <p>Overall, 790 patients were assessed as eligible for ART based on their clinical and/or immunological status among whom 510 (64.6%) started treatment, 26 (3.3%) requested transfer to another health facility, 136 (17.2%) and 118 (14.9%) were lost to follow-up and died respectively without starting ART. ART-eligible patients who died or were lost to follow-up were more likely to be male or to have a CD4 T-cell count < 100 cells/μL, while patients in WHO clinical stage 3 or 4 were more likely to die without starting treatment. The overall pre-treatment mortality rate was 21.9 deaths per 100 person-years (95% CI 18.3 - 26.2) and the rate for the composite end point of death or loss to follow-up was 47.1 per 100 person-years (95% CI 41.6 - 53.2). Independent predictors of pre-treatment mortality were CD4 T-cell count <100 cells/μL (adjusted Hazard ratio [AHR] 3.71; 95%CI 2.54 - 5.41) and WHO stage 3 or 4 disease (AHR 1.91; 95% CI 1.12 - 3.23). Forty percent of ART-eligible patients lost to follow-up seen alive at field visit cited difficulty with the requirement of disclosing their HIV status as reason for not starting ART.</p> <p>Conclusion</p> <p>Approximately one third of ART-eligible patients did not start ART and pre-treatment mortality rate was found high among HIV infected patients in our cohort. CD4 T-cell count <100 cells/μL is the strongest independent predictor of pre-treatment mortality. The requirement to disclose HIV status as part of ART preparation counselling constitutes a huge barrier for eligible patients to access treatment.</p

Unpredictability dictates quality of maternal and newborn care provision in rural Tanzania-A qualitative study of health workers' perspectives.

BACKGROUND: Health workers are the key to realising the potential of improved quality of care for mothers and newborns in the weak health systems of Sub Saharan Africa. Their perspectives are fundamental to understand the effectiveness of existing improvement programs and to identify ways to strengthen future initiatives. The objective of this study was therefore to examine health worker perspectives of the conditions for maternal and newborn care provision and their perceptions of what constitutes good quality of care in rural Tanzanian health facilities. METHODS: In February 2014, we conducted 17 in-depth interviews with different cadres of health workers providing maternal and newborn care in 14 rural health facilities in Tandahimba district, south-eastern Tanzania. These facilities included one district hospital, three health centres and ten dispensaries. Interviews were conducted in Swahili, transcribed verbatim and translated into English. A grounded theory approach was used to guide the analysis, the output of which was one core category, four main categories and several sub-categories. RESULTS: 'It is like rain' was identified as the core category, delineating unpredictability as the common denominator for all aspects of maternal and newborn care provision. It implies that conditions such as mothers' access to and utilisation of health care are unreliable; that availability of resources is uncertain and that health workers have to help and try to balance the situation. Quality of care was perceived to vary as a consequence of these conditions. Health workers stressed the importance of predictability, of 'things going as intended', as a sign of good quality care. CONCLUSIONS: Unpredictability emerged as a fundamental condition for maternal and newborn care provision, an important determinant and characteristic of quality in this study. We believe that this finding is also relevant for other areas of care in the same setting and may be an important defining factor of a weak health system. Increasing predictability within health services, and focusing on the experience of health workers within these, should be prioritised in order to achieve better quality of care for mothers and newborns

The use of fluorescent probes to characterize conformational changes in the interaction between vitronectin and plasminogen activator inhibitor-1

Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue-type plasminogen activator and urokinase, is known to convert readily to a latent form by insertion of the reactive center loop into a central β- sheet. Interaction with vitronectin stabilizes PAI-1 and decreases the rate of conversion to the latent form, but conformational effects of vitronectin on the reactive center loop of PAI-1 have not been documented. Mutant forms of PAI-1 were designed with a cysteine substitution at either position P1\u27 or P9 of the reactive center loop. Labeling of the unique cysteine with a sulfhydryl-reactive fluorophore provides a probe that is sensitive to vitronectin binding. Results indicate that the scissile P1-P1\u27 bond of PAI-1 is more solvent exposed upon interaction with vitronectin, whereas the N- terminal portion of the reactive loop does not experience a significant change in its environment. These results were complemented by labeling vitronectin with an arginine-specific coumarin probe which compromises heparin binding but does not interfere with PAI-1 binding to the protein. Dissociation constants of approximately 100 nM are calculated for the vitronectin/PAI-1 interaction from titrations using both fluorescent probes. Furthermore, experiments in which PAI-1 failed to compete with heparin for binding to vitronectin argue for separate binding sites for the two ligands on vitronectin

Study protocol: the effects of air pollution exposure and chronic respiratory disease on pneumonia risk in urban Malawian adults - the Acute Infection of the Respiratory Tract Study (The AIR Study)

Background Pneumonia is the 2nd leading cause of years of life lost worldwide and is a common cause of adult admissions to hospital in sub-Saharan Africa. Risk factors for adult pneumonia are well characterised in developed countries, but are less well described in sub-Saharan Africa where HIV is a major contributing factor. Exposure to indoor and outdoor air pollution is high, and tobacco smoking prevalence is increasing in sub-Saharan Africa, yet the contribution of these factors to the burden of chronic respiratory diseases in sub-Saharan Africa remains poorly understood. Furthermore, the extent to which the presence of chronic respiratory diseases and exposure to air pollution contribute to the burden of pneumonia is not known. Design The Acute Infection of the Respiratory Tract Study (The AIR Study) is a case–control study to identify preventable risk factors for adult pneumonia in the city of Blantyre, Malawi. Cases will be adults admitted with pneumonia, recruited from Queen Elizabeth Central Hospital, the largest teaching hospital in Malawi. Controls will be adults without pneumonia, recruited from the community. The AIR Study will recruit subjects and analyse data within strata defined by positive and negative HIV infection status. All participants will undergo thorough assessment for a range of potential preventable risk factors, with an emphasis on exposure to air pollution and the presence of chronic respiratory diseases. This will include collection of questionnaire data, clinical samples (blood, urine, sputum and breath samples), lung function data and air pollution monitoring in their home. Multivariate analysis will be used to identify the important risk factors contributing to the pneumonia burden in this setting. Identification of preventable risk factors will justify research into the effectiveness of targeted interventions to address this burden in the future. Discussion The AIR Study is the first study of radiologically confirmed pneumonia in which air pollution exposure measurements have been undertaken in this setting, and will contribute important new information about exposure to air pollution in urban SSA. Through identification of preventable risk factors, the AIR Study aims to facilitate future research and implementation of targeted interventions to reduce the high burden of pneumonia in SSA

Use of an electronic medical record to monitor efficacy of diabetes care in out-patients in a central hospital in Malawi: Patterns of glycaemic control and lessons learned

The Malawian health sector has a strong tradition of systematic data collection for monitoring and evaluation of large-scale services. A highly successful adapted Directly Observed Treatment, Short course “DOTS” framework, based on patient registers and paperbased mastercards was introduced to facilitate the management and monitoring of the scale up of antiretroviral therapy. Subsequently, a simple, touch-screen based electronic medical record system (EMRs) was effectively introduced at high burden ART sites. Based on this model, in 2010, a diabetes specific EMRs was introduced in the diabetes clinic at Queen Elizabeth Central Hospital. In this paper we report on the first 3 years experience with the diabetes EMRs. We highlight the strengths and weaknesses of the diabetes EMRs and present data on glycaemic control recorded in the system

Household air pollution, chronic respiratory disease and pneumonia in Malawian adults: A case-control study

Background: Four million people die each year from diseases caused by exposure to household air pollution. There is an association between exposure to household air pollution and pneumonia in children (half a million attributable deaths a year); however, whether this is true in adults is unknown. We conducted a case-control study in urban Malawi to examine the association between exposure to household air pollution and pneumonia in adults. Methods: Hospitalized patients with radiologically confirmed pneumonia (cases) and healthy community controls underwent 48 hours of ambulatory and household particulate matter (µg/m3) and carbon monoxide (ppm) exposure monitoring. Multivariate logistic regression, stratified by HIV status, explored associations between these and other potential risk factors with pneumonia. Results: 145 (117 HIV-positive; 28 HIV-negative) cases and 253 (169 HIV-positive; 84 HIV-negative) controls completed follow up. We found no evidence of association between household air pollution exposure and pneumonia in HIV-positive (e.g. ambulatory particulate matter adjusted odds ratio [aOR] 1.00 [95% CI 1.00–1.01, p=0.141]) or HIV-negative (e.g. ambulatory particulate matter aOR 1.00 [95% CI 0.99–1.01, p=0.872]) participants. Chronic respiratory disease was associated with pneumonia in both HIV-positive (aOR 28.07 [95% CI 9.29–84.83, p<0.001]) and HIV-negative (aOR 104.27 [95% CI 12.86–852.35, p<0.001]) participants. Conclusions: We found no evidence that exposure to household air pollution is associated with pneumonia in Malawian adults. In contrast, chronic respiratory disease was strongly associated with pneumonia

Seroprevalence of hepatitis B and C virus in HIV-1 and HIV-2 infected Gambians

BACKGROUND: The prevalence of HIV/hepatitis co-infection in sub-Saharan Africa is not well documented, while both HIV and HBV are endemic in this area. OBJECTIVE: The aim of this study is to determine the seroprevalence of HBV and HCV virus in HIV-infected subjects in the Gambia. METHODS: Plasma samples from HIV infected patients (190 individuals with clinically defined AIDS and 382 individuals without AIDS) were tested retrospectively for the presence of HBV sero-markers and for serum HBV DNA, screened for HCV infection by testing for anti-HCV antibody and HCV RNA. RESULTS: HBsAg prevalence in HIV-positive individuals is 12.2%. HIV/HBV co-infected individuals with CD4 count of <200 cells µL⁻¹ have a higher HBV DNA viral load than patients with higher CD4 count (log 4.0 vs. log 2.0 DNA copies/ml, p < 0.05). Males (OR = 1.8, 95% CI: 1.0, 3.2) were more likely to be HBsAg positive than female. HCV seroprevalence was 0.9% in HIV-positive individuals. CONCLUSION: The prevalence of HBsAg carriage in HIV- infected Gambians is similar to that obtained in the general population. However co-infected individuals with reduced CD4 levels, indicative of AIDS had higher prevalence of HBeAg retention and elevated HBV DNA levels compared to non-AIDS patients with higher CD4 count

The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression

Mutations in the gene autoimmune regulator (AIRE) cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. AIRE is expressed in thymic medullary epithelial cells, where it promotes the expression of tissue-restricted antigens. By the combined use of biochemical and biophysical methods, we show that AIRE selectively interacts with histone H3 through its first plant homeodomain (PHD) finger (AIRE–PHD1) and preferentially binds to non-methylated H3K4 (H3K4me0). Accordingly, in vivo AIRE binds to and activates promoters containing low levels of H3K4me3 in human embryonic kidney 293 cells. We conclude that AIRE–PHD1 is an important member of a newly identified class of PHD fingers that specifically recognize H3K4me0, thus providing a new link between the status of histone modifications and the regulation of tissue-restricted antigen expression in thymus

Grazing and No-Till Cropping Impacts on Nitrogen Retention in Dryland Agroecosystems

As the world\u27s population increases, marginal lands such as drylands are likely to become more important for food production. One proven strategy for improving crop production in drylands involves shifting from conventional tillage to no-till to increase water use efficiency, especially when this shift is coupled with more intensive crop rotations. Practices such as no-till that reduce soil disturbance and increase crop residues may promote C and N storage in soil organic matter, thus promoting N retention and reducing N losses. By sampling soils 15 yr after a N tracer addition, this study compared long-term soil N retention across several agricultural management strategies in current and converted shortgrass steppe ecosystems: grazed and ungrazed native grassland, occasionally mowed planted perennial grassland, and three cropping intensities of no-till dryland cropping. We also examined effects of the environmental variables site location and topography on N retention. Overall, the long-term soil N retention of \u3e18% in these managed semiarid ecosystems was high compared with published values for other cropped or grassland ecosystems. Cropping practices strongly influenced long-term N retention, with planted perennial grass systems retaining \u3e90% of N in soil compared with 30% for croplands. Grazing management, topography, and site location had smaller effects on long-term N retention. Estimated 15-yr N losses were low for intact and cropped systems. This work suggests that semiarid perennial grass ecosystems are highly N retentive and that increased intensity of semiarid land management can increase the amount of protein harvested without increasing N losses

Response to “prognostic biomarkers in oral leukoplakia”

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152757/1/odi13185.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152757/2/odi13185_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152757/3/odi13185-sup-0001-AppendixS1.pd