Cytopenias among ART-naive patients with advanced HIV disease on enrolment to care and treatment services at a tertiary hospital in Tanzania: A crosssectional study

Background: HIV/AIDS causes high morbidity and mortality through both immunosuppression and complications not directly related to immunosuppression. Haematological abnormalities, including various cytopenias, occur commonly in HIV through immune and non-immune pathways. Though these complications could potentially cause serious clinical implications, published literature on the magnitude of this problem and its associated factors in Tanzania is scarce. This study aimed at determining the prevalence and risk factors of HIV-associated cytopenias among ART-naive patients enrolling for care and treatment services at Bugando Care and Treatment Centre (CTC) in Mwanza, Tanzania.Methods: This was a cross-sectional clinic-based study done between March 2015 and February 2016, involving all antiretroviral therapy (ART)-naive adult HIV positive patients enrolling for care and treatment services at Bugando CTC. Patients younger than 18 years and those with missing data were excluded. Data were analysed using Stata version 11 to determine the prevalence and risk factors of cytopenias.Results: A total of 1205 ART-naive patients were included. Median age was 41 years (interquartile range [IQR] 32 to 48). Most participants were female (n = 789; 65.6%), with a female-to-male ratio of 2:1. The median baseline CD4 count was 200 cells/μL (IQR 113 to 439). About half (49%) of the study participants had baseline CD4 counts less than 200 cells/μL. Anaemia, leucopenia, and thrombocytopenia were found in 704 (58.4%), 285 (23.6%), and 174 (14.4%) participants, respectively, and these were strongly associated with advanced HIV infection.Conclusions: The magnitude of cytopenias is high among ART-naive HIV-positive adults, and cytopenias are more marked with advanced HIV infection. Early diagnosis of HIV and timely initiation of ART could potentially reduce the number of people living with advanced HIV disease and its associated complications, including the cytopenias investigated in this study. Patients with cytopenias should undergo thorough screening for tuberculosis, which is an important and treatable correlate of cytopenia, in addition to close follow-up for any potential negative outcomes

Modeling and measuring intracellular fluxes of secreted recombinant protein in Pichia pastoris with a novel 34S labeling procedure

<p>Abstract</p> <p>Background</p> <p>The budding yeast <it>Pichia pastoris </it>is widely used for protein production. To determine the best suitable strategy for strain improvement, especially for high secretion, quantitative data of intracellular fluxes of recombinant protein are very important. Especially the balance between intracellular protein formation, degradation and secretion defines the major bottleneck of the production system. Because these parameters are different for unlimited growth (shake flask) and carbon-limited growth (bioreactor) conditions, they should be determined under "production like" conditions. Thus labeling procedures must be compatible with minimal production media and the usage of bioreactors. The inorganic and non-radioactive ³⁴S labeled sodium sulfate meets both demands.</p> <p>Results</p> <p>We used a novel labeling method with the stable sulfur isotope ³⁴S, administered as sodium sulfate, which is performed during chemostat culivations. The intra- and extracellular sulfur 32 to 34 ratios of purified recombinant protein, the antibody fragment Fab3H6, are measured by HPLC-ICP-MS. The kinetic model described here is necessary to calculate the kinetic parameters from sulfur ratios of consecutive samples as well as for sensitivity analysis. From the total amount of protein produced intracellularly (143.1 μg g^-1h^-1protein per yeast dry mass and time) about 58% are degraded within the cell, 35% are secreted to the exterior and 7% are inherited to the daughter cells.</p> <p>Conclusions</p> <p>A novel ³⁴S labeling procedure that enables <it>in vivo </it>quantification of intracellular fluxes of recombinant protein under "production like" conditions is described. Subsequent sensitivity analysis of the fluxes by using MATLAB, indicate the most promising approaches for strain improvement towards increased secretion.</p

Control of hypertension among diabetic patients in a referral hospital in Tanzania: a cross-sectional study

Background: Hypertension is common among diabetic patients. The co-existence of two conditions carries an excessive risk of severe complications and mortalities. Limited information exists on the determinants of poor hypertension control among these patients. We aimed at determining the prevalence and factors associated with poor hypertension control in these patients. Methods: Data of diabetic patients who were also hypertensive attending an outpatient clinic from 1 August 2015 to 31 December 2015 at Bugando Medical Centre were retrospectively analyzed. Uncontrolled hypertension was defined as a blood pressure of ≥130mmHg and/or ≥80mmHg systolic and diastolic respectively. A designed questionnaire was used to collect data of patients. Continuous variables were summarized by median and interquartile ranges (IQR) and categorical variables were summarized by frequency and percentage. Logistic regression was used to find the predictors of uncontrolled hypertension. Results: The majority of our study population were females, 161/295 (54.6%), and the median age was 57 years (IQR 50-64). The prevalence of hypertension was 206/295 (69.8%). A total of 174/206 (84.5%) patients had uncontrolled hypertension. This poor control was significantly associated with poor adherence to anti-hypertensives (OR 1.73[1.26-2.38] p=0.002), presence of any long-term complication (OR 3.19 [1.65-6.18] p=0.03) and overweight (BMI\u3e24.9 Vs. Conclusion: The prevalence of poor hypertension control among diabetic patients in Tanzania is alarming. Most of the factors associated with this situation can be modified. The clinicians should advocate individualized management, continuous health education and adherence to the available guidelines

Risk factors for mortality among tuberculosis patients on treatment at Bugando Medical Centre in north-western Tanzania: a retrospective cross-sectional study

 Background: Tuberculosis (TB) is still an important cause of morbidity and mortality worldwide. Though it can effectively be treated, still a significant proportion of patients die on the course of their treatment. The objective of this study was to determine the outcome and risk factors of mortality among patients diagnosed with TB in a tertiary hospital in north-western Tanzania.Methods: A retrospective cross sectional study was done among all patients diagnosed with TB between January and December 2015 at Bugando Medical Centre. Information of demographic characteristics, smear positivity, haemoglobin concentration, HIV status, CD4 counts for HIV positive patients and treatment outcomes were collected and analysed. TB treatment outcomes as dead or alive were calculated and logistic regression was done to determine the factors associated with increased risk of death of patients on anti-TB treatment.Results: In total 701 patients were diagnosed with TB during the study period. Of these, 361 (51.5%) were males with a median age of 38 (IQR 27- 47) and 421 (60.06%) were younger than 40 years. Majority of the participants 409 (58.35%) had smear positive pulmonary tuberculosis and about half of patients (51.07%) tested positive for HIV. Of the enrolled patients 610 (87.02%) were alive at the end of TB treatment while 91 (12.98%) died in the course of treatment. The odds of deaths of patients on anti-TB treatment were strongly associated with male sex, HIV co infection and severe anaemia.Conclusion: The proportion of patients who die from TB treatment at BMC is high, with an increased risk of death among HIV co-infected, older than 40 years and severely anaemic patients. Improvement of strategies for early diagnosis and prompt treatment of TB patients will potentially improve treatment outcome

COST-EFFECTIVENESS ANALYSIS IN THE MANAGEMENT OF STROKE

Objective: Stroke is one of the leading causes of death and disabilities worldwide. Cost-effectiveness analysis helps identify neglected opportunities by highlighting interventions that are relatively inexpensive, yet have the potential to reduce the disease burden substantially. In India, there are wide social and economic disparities. Socioeconomic environment influences occupation, lifestyle, and nutrition of social classes which in turn would influence the prevalence and profile of stroke. By reduction of delays in access to hospital and improving provision of affordable treatments can reduce morbidity and mortality in patients with stroke in India. This study is designed to measure and compare the costs (resources consumed) and consequences (clinical, economic, and humanistic) of pharmaceutical products and services and their impact on individuals, healthcare systems and society.Methods: The purpose of this study is to analyze and conduct a cost-effectiveness analysis for the treatment of stroke in Guntur City Hospitals. The patients were treated either with aspirin or clopidogrel. The health outcomes were measured using Modified Rankin Scale, A prominent risk assessment scale for stroke. The pharmacoeconomic data were computed from the patient data collection forms.Result: The incremental cost-effectiveness ratio of aspirin and clopidogrel were calculated to be Rs. 8046.2/year.Conclusion: The study concludes that aspirin has the increased socioeconomic impact when compared to Clopidogrel and we can see that the earlier therapy has supported discharge, home-based rehabilitation along with reduced hospital stay and hence preferable

Prevalence and Risk Factors of Delayed Sputum Conversion among Patients Treated for Smear Positive PTB in Northwestern Rural Tanzania: A Retrospective Cohort Study

Introduction. Smear positive TB carries high morbidity and mortality. The TB treatment aims at sputum conversion by two months of antituberculous. Patients who delay sputum conversion remain potentially infectious, with risk of treatment failure, drug resistance, and mortality. Little is known about the magnitude of this problem in our setting. This study was designed to determine the prevalence and risk factors of delayed sputum conversion in northwestern rural part of Tanzania. Methods. This was a retrospective cohort study involving smear positive TB patients at Sengerema DDH in 2015. Demographic data, HIV status, and sputum results at TB diagnosis and on TB treatment were collected and analyzed using STATA 11. Results. In total, 156 patients were studied. Males were 97 (62%); the median age was 39 [30–51] years. Fifty-five (35.3%) patients were HIV coinfected and 13 (8.3%) patients had delayed sputum conversion which was strongly associated with male gender (OR=8.2, p=0.046), age >50 years (OR=6.7, p=0.003), and AFB 3+ (OR=8.1, p=0.008). Conclusions. Delayed sputum conversion is prevalent in this study. These patients can potentially fail on treatment, develop drug resistance, and continue spreading TB. Strategies to reduce the rate of delayed sputum conversion could also reduce these potential unfavorable outcomes

Liver Fibrosis and Hepatitis B Coinfection among ART Naïve HIV-Infected Patients at a Tertiary Level Hospital in Northwestern Tanzania: A Cross-Sectional Study

Background. Liver fibrosis which is a common complication of chronic hepatitis B infection is rarely diagnosed in low-resource countries due to limited capacity to perform biopsy studies. Data on the utilization of noninvasive techniques which are feasible for diagnosis of liver fibrosis in these settings among HIV-infected patients is scarce. The objective of this study was to establish the magnitude of liver fibrosis by using both aspartate-aminotransferase-to-platelets ratio and fibrosis-4 scores with associated hepatitis B coinfection among antiretroviral therapy naïve HIV-infected patients. Methods. We reviewed data of 743 adult patients attending HIV clinic with available hepatitis B surface antigen test results. Baseline clinical information was recorded and aspartate-aminotransferase-to-platelet ratio and fibrosis-4 scores were calculated. The cut-off values of 1.5 and 3.25 were used for diagnosis of significant fibrosis by aspartate-aminotransferase-to-platelets ratio and fibrosis-4 scores, respectively. Results. The prevalence of liver fibrosis was 3.5% when aspartate-aminotransferase-to-platelet score was used and 4.6% with fibrosis-4 score and they were both significantly higher among patients with hepatitis B coinfection. Younger patients with HIV advanced disease and elevated liver transaminases had increased risk of having hepatitis B coinfection. Conclusion. A remarkable number of HIV-infected patients present with liver fibrosis, predominantly those with hepatitis B infection

Participant understanding of informed consent in a multidisease community-based health screening and biobank platform in rural South Africa.

BACKGROUND: In low- and middle-income settings, obtaining informed consent for biobanking may be complicated by socio-economic vulnerability and context-specific power dynamics. We explored participants experiences and perceptions of the research objectives in a community-based multidisease screening and biospecimen collection platform in rural KwaZulu-Natal, South Africa. METHODS: We undertook semi-structured in-depth interviews to assess participant understanding of the informed consent, research objectives and motivation for participation. RESULTS: Thirty-nine people participated (individuals who participated in screening/biospecimen collection and those who did not and members of the research team). Some participants said they understood the information shared with them. Some said they participated due to the perceived benefits of the reimbursement and convenience of free healthcare. Most who did not participate said it was due to logistical rather than ethical concerns. None of the participants recalled aspects of biobanking and genetics from the consent process. CONCLUSIONS: Although most people understood the study objectives, we observed challenges to identifying language appropriate to explain biobanking and genetic testing to our target population. Engagement with communities to adopt contextually relevant terminologies that participants can understand is crucial. Researchers need to be mindful of the impact of communities' socio-economic status and how compensation can be potentially coercive

Seroprevalence of hepatitis B virus infection, anti-HCV antibodies and HIV and knowledge among people who use drugs attending methadone therapy clinic in Tanzania; a cross-sectional study

Background Methadone therapy clinics have been recently introduced in Tanzania, aiming at reducing risk behaviors and infection rates of viral hepatitis and HIV among people who use drugs. The objective of this study was to estimate the prevalence, associated factors and knowledge level of these conditions among people who use drugs attending a methadone clinic in Tanzania. Methods We enrolled 253 People who using drugs receiving Methadone therapy. Clinical data was retrospectively collected from the medical records and face-to face interviews were conducted to determine the behavioral risk factors and respondents’ knowledge on viral hepatitis and HIV. Results An overall seroprevalence of viral hepatitis (either hepatitis B surface antigen or anti-hepatitis C virus) was 6.3%, while that of hepatitis B virus mono infection was 3.5% and anti-hepatitis C antibodies was 3.5%. Seroprevalence of HIV was 12.6%. Viral hepatitis was strongly predicted by advanced age (\u3e 35 years) (p = 0.02) and staying at Kirumba area (p = 0.004), and HIV infection was predicted by increased age (\u3e 37 years) (p = 0.04) and female sex (p \u3c 0.001). Regarding the knowledge of viral hepatitis, majority of the respondents were unaware of the transmission methods and availability of hepatitis B virus vaccines and only 17% were classified as well informed (provided ≥4 correct answers out of 7 questions). Good knowledge was highly predicted by higher education level of the individual (p = 0.001). Conclusions Despite the efforts to curb viral hepatitis and HIV infections through Methadone clinics, infection rates among people who use drugs are still high and the general knowledge on preventive measures is inadequate

Ubiquitous Aberration in Cholesterol Metabolism Across Pancreatic Ductal Adenocarcinoma

Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired by PC cells. Nevertheless, the significance of the de novo cholesterol synthesis pathway has been controversial in PC, indicating the need to reassess this pathway in PC. We utilized preclinical models and clinical specimens of PC patients and cell lines and utilized mass spectrometry-based sterol analysis. Further, we also performed in silico analysis to corroborate the significance of de novo cholesterol synthesis pathway in PC. Our results demonstrated alteration in free sterol levels, including free cholesterol, across in vitro, in vivo, and clinical specimens of PC. Especially, our sterol analyses established consistent alterations in free cholesterol across the different PC models. Overall, this study demonstrates the significance and consistency in deviation of cholesterol synthesis pathway in PC while showing the aberrations in sterol metabolite intermediates and the related genes using preclinical models, in silico platforms, and the clinical specimens