728 research outputs found

    A Comparison of Miltefosine and Sodium Stibogluconate for Treatment of Visceral Leishmaniasis in an Ethiopian Population with High Prevalence of HIV Infection.

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    BACKGROUND: Antimonials are the mainstay of visceral leishmaniasis (VL) treatment in Africa. The increasing incidence of human immunodeficiency virus (HIV) coinfection requires alternative safe and effective drug regimens. Oral miltefosine has been proven to be safe and effective in the treatment of Indian VL but has not been studied in Africa or in persons with HIV and VL coinfection. METHODS: We compared the efficacy of miltefosine and sodium stibogluconate (SSG) in the treatment of VL in persons in Ethiopia. A total of 580 men with parasitologically and/or serologically confirmed VL were randomized to receive either oral miltefosine (100 mg per day for 28 days) or intramuscular SSG (20 mg/kg per day for 30 days). RESULTS: The initial cure rate was 88% in both treatment groups. Mortality during treatment was 2% in the miltefosine group, compared with 10% in the SSG group. Initial treatment failure was 8% in the miltefosine group, compared with 1% in the SSG group. Among the 375 patients (65%) who agreed to HIV testing, HIV seroprevalence was 29%. Among patients not infected with HIV, initial cure, mortality, and initial treatment failure rates were not significantly different (94% vs. 95%, 1% vs. 3%, and 5% vs. 1% for the miltefosine and SSG groups, respectively). Initial treatment failure with miltefosine occurred in 18% of HIV-coinfected patients, compared with treatment failure in 5% of non-HIV-infected patients. At 6 months after treatment, 174 (60%) of the 290 miltefosine recipients and 189 (65%) of the 290 SSG recipients experienced cure; 30 (10%) of 290 in the miltefosine group and 7 (2%) of 290 in the SSG group experienced relapse, and the mortality rate was 6% in the miltefosine group, compared with 12% in the SSG group. HIV-infected patients had higher rates of relapse (16 [25%] of 63 patients), compared with non-HIV-infected patients (5 [5%] of 131). CONCLUSIONS: Treatment with miltefosine is equally effective as standard SSG treatment in non-HIV-infected men with VL. Among HIV-coinfected patients, miltefosine is safer but less effective than SSG

    Conservation and “land grabbing” in rangelands: Part of the problem or part of the solution?

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    Large-scale land acquisitions have increased in scale and pace due to changes in commodity markets, agricultural investment strategies, land prices, and a range of other policy and market forces. The areas most affected are the global “commons” – lands that local people traditionally use collectively — including much of the world’s forests, wetlands, and rangelands. In some cases land acquisition occurs with environmental objectives in sight – including the setting aside of land as protected areas for biodiversity conservation. On the other hand, current trends and patterns of commercial land acquisition present a major and growing threat not just to local livelihoods and human rights, but also to conservation objectives. There is a potential opportunity here for greater collaboration between conservation interests, and local communities’ land rights interests with their supporters amongst human rights and social justice movements. This Issue Paper documents experiences from the rangelands of Mongolia, Kenya, India, Ethiopia, and other countries, which were presented at a Conference on Conservation and Land Grabbing held in London in 2013

    MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer : The hOrmone and Diet in the ETiology of breast cancer prospective study

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    report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR- 513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk

    Factors in the suboptimum performance of rural water supply systems in the Ethiopian highlands

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    Access to safe drinking water services in the Ethiopian Highlands is one of lowest worldwide due to failure of water supply services shortly after construction. Over hundred water supply systems were surveyed to find the underlying causes of failure and poor performance throughout the Amhara Regional State. The results show generally that systems with decision-making power at the community level during design and construction remained working longer than when the decisions were made by a central authority. In addition, the sustainability was better for water systems that were farther away from alternative water resources and contributed more cash and labour. The results of this study of the importance of decision-making at the local level in contrast to the central authority is directly applicable to the introduction of rain water management systems as shown by earlier efforts of installing rain water harvesting systems in the Ethiopian highlands

    A randomized controlled trial of the effects of a prudent diet on cardiovascular risk factors, gene expression, and DNA methylation - the Diet and Genetic Intervention (DIGEST) Pilot study

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    Background Risk of cardiovascular disease (CVD) can be increased by single-nucleotide polymorphisms (SNPs) in the 9p21 region of the genome. However, observational studies have shown that the deleterious effect of 9p21 SNPs on CVD might be offset by consuming a diet rich in fresh fruits and vegetables. This association may be driven by diet-influenced modifications in epigenetic and gene expression profiles. In this pilot study, we aimed to: i. test the feasibility of provision of a ‘Prudent’ and ‘Western’ diet outside of a specialized clinic, ii. assess the impact of each diet on cardiovascular risk factors. Methods A single centre, parallel two-arm, pilot randomized controlled trial (RCT) with food provision was conducted in a university teaching hospital outpatient clinic (McMaster university, Hamilton, ON, Canada). The aim was to recruit 80 participants, which allowed for a 10 % dropout. The actual study consisted of 84 apparently healthy participants (69 % women, 18 to 77 years) at low cardiovascular risk. Participants were randomly assigned to follow one of two weight-maintaining diets: ‘Prudent’ or ‘Western’ for 2-weeks. The Prudent diet provided 92 % of provided food consumed). The Prudent diet was 48 % more palatable than the Western diet (P < 0.05). Participants receiving the Prudent diet showed a trend toward reduced systolic (-4 mmHg; P = 0.10) and diastolic (-3 mmHg; P = 0.07) blood pressure, and total cholesterol (-0.24 mmol/L; P = 0.08), compared to individuals receiving the Western diet. Data collection from all randomized participants was completed within 18 months. Conclusions Recruitment, and retention of apparently healthy, normotensive adults into a feeding study for a 2-week duration is feasible outside of specialized dietary clinic, and modest diet-related changes in biomarkers begin to appear after two weeks

    Multicentre validation of the bedside paediatric early warning system score: a severity of illness score to detect evolving critical illness in hospitalised children

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    Abstract Introduction The timely provision of critical care to hospitalised patients at risk for cardiopulmonary arrest is contingent upon identification and referral by frontline providers. Current approaches require improvement. In a single-centre study, we developed the Bedside Paediatric Early Warning System (Bedside PEWS) score to identify patients at risk. The objective of this study was to validate the Bedside PEWS score in a large patient population at multiple hospitals. Methods We performed an international, multicentre, case-control study of children admitted to hospital inpatient units with no limitations on care. Case patients had experienced a clinical deterioration event involving either an immediate call to a resuscitation team or urgent admission to a paediatric intensive care unit. Control patients had no events. The scores ranged from 0 to 26 and were assessed in the 24 hours prior to the clinical deterioration event. Score performance was assessed using the area under the receiver operating characteristic (AUCROC) curve by comparison with the retrospective rating of nurses and the temporal progression of scores in case patients. Results A total of 2,074 patients were evaluated at 4 participating hospitals. The median (interquartile range) maximum Bedside PEWS scores for the 12 hours ending 1 hour before the clinical deterioration event were 8 (5 to 12) in case patients and 2 (1 to 4) in control patients (P < 0.0001). The AUCROC curve (95% confidence interval) was 0.87 (0.85 to 0.89). In case patients, mean scores were 5.3 at 20 to 24 hours and 8.4 at 0 to 4 hours before the event (P < 0.0001). The AUCROC curve (95% CI) of the retrospective nurse ratings was 0.83 (0.81 to 0.86). This was significantly lower than that of the Bedside PEWS score (P < 0.0001). Conclusions The Bedside PEWS score identified children at risk for cardiopulmonary arrest. Scores were elevated and continued to increase in the 24 hours before the clinical deterioration event. Prospective clinical evaluation is needed to determine whether this score will improve the quality of care and patient outcomes
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