The effect of HIV counselling and testing on HIV acquisition in sub-Saharan Africa: a systematic review

Annually, millions of people in sub-Saharan Africa (SSA) receive HIV counselling and testing (HCT), a service designed to inform persons of their HIV status and, if HIV-uninfected, reduce HIV acquisition risk. However, the impact of HCT on HIV acquisition has not been systematically evaluated. We conducted a systematic review to assess this relationship in SSA

An evaluation of the Elementary Evaluative Criteria

Thesis (Ed.M.)--Boston University, 1955. This item was digitized by the Internet Archive

Prediction of liver disease in patients whose liver function tests have been checked in primary care : model development and validation using population-based observational cohorts

This work was supported by the UK National Health Service Research & Development Programme Health Technology Assessment Programme (project number 03/38/02) and also by the Backett Weir Russell Career Development Fellowship, University of Aberdeen.OBJECTIVE: To derive and validate a clinical prediction model to estimate the risk of liver disease diagnosis following liver function tests (LFTs) and to convert the model to a simplified scoring tool for use in primary care. DESIGN: Population-based observational cohort study of patients in Tayside Scotland identified as having their LFTs performed in primary care and followed for 2 years. Biochemistry data were linked to secondary care, prescriptions and mortality data to ascertain baseline characteristics of the derivation cohort. A separate validation cohort was obtained from 19 general practices across the rest of Scotland to externally validate the final model. SETTING: Primary care, Tayside, Scotland. PARTICIPANTS: Derivation cohort: LFT results from 310 511 patients. After exclusions (including: patients under 16 years, patients having initial LFTs measured in secondary care, bilirubin >35 μmol/L, liver complications within 6 weeks and history of a liver condition), the derivation cohort contained 95 977 patients with no clinically apparent liver condition. Validation cohort: after exclusions, this cohort contained 11 653 patients. PRIMARY AND SECONDARY OUTCOME MEASURES: Diagnosis of a liver condition within 2 years. RESULTS: From the derivation cohort (n=95 977), 481 (0.5%) were diagnosed with a liver disease. The model showed good discrimination (C-statistic=0.78). Given the low prevalence of liver disease, the negative predictive values were high. Positive predictive values were low but rose to 20-30% for high-risk patients. CONCLUSIONS: This study successfully developed and validated a clinical prediction model and subsequent scoring tool, the Algorithm for Liver Function Investigations (ALFI), which can predict liver disease risk in patients with no clinically obvious liver disease who had their initial LFTs taken in primary care. ALFI can help general practitioners focus referral on a small subset of patients with higher predicted risk while continuing to address modifiable liver disease risk factors in those at lower risk.Publisher PDFPeer reviewe

Hidden costs: The ethics of cost-effectiveness analyses for health interventions in resource-limited settings

Cost-effectiveness analysis (CEA) is an increasingly appealing tool for evaluating and comparing health-related interventions in resource-limited settings. The goal is to inform decision-makers regarding the health benefits and associated costs of alternative interventions, helping guide allocation of limited resources by prioritizing interventions that offer the most health for the least money. Although only one component of a more complex decision-making process, CEAs influence the distribution of healthcare resources, directly influencing morbidity and mortality for the world’s most vulnerable populations. However, CEA-associated measures are frequently setting-specific valuations, and CEA outcomes may violate ethical principles of equity and distributive justice. We examine the assumptions and analytical tools used in CEAs that may conflict with societal values. We then evaluate contextual features unique to resource-limited settings, including the source of health-state utilities and disability weights; implications of CEA thresholds in light of economic uncertainty; and the role of external donors. Finally, we explore opportunities to help align interpretation of CEA outcomes with values and budgetary constraints in resource-limited settings. The ethical implications of CEAs in resource-limited settings are vast. It is imperative that CEA outcome summary measures and implementation thresholds adequately reflect societal values and ethical priorities in resource-limited settings

The impact of the abuse-deterrent reformulation of extended-release T OxyContin on prescription pain reliever misuse and heroin initiation

The introduction of abuse-deterrent OxyContin in 2010 was intended to reduce its misuse by making it more tamper resistant. However, some studies have suggested that this reformulation might have had unintended consequences, such as increases in heroin-related deaths. We used the 2005–2014 cross-sectional U.S. National Survey on Drug Use and Health to explore the impact of this reformulation on intermediate outcomes that precede heroin-related deaths for individuals with a history of OxyContin misuse. Our study sample consisted of adults who misused any prescription pain reliever prior to the reformulation of OxyContin (n = 81,400). Those who misused OxyContin prior to the reformulation were considered the exposed group and those who misused other prescription pain relievers prior to the reformulation were considered the unexposed group. We employed multivariate logistic regression under a difference-in-differences framework to examine the effect of the re- formulation on five dichotomous outcomes: prescription pain reliever misuse; prescription pain reliever use disorder; heroin use; heroin use disorder; and heroin initiation. We found a net reduction in the odds of pre- scription pain reliever misuse (OR:0.791, p \u3c 0.001) and heroin initiation (OR:0.422, p = 0.011) after the reformulation for the exposed group relative to the unexposed group. We found no statistically significant effects of the reformulation on prescription pain reliever use disorder (OR: 0.934, p = 0.524), heroin use (OR: 1.014p = 0.941), and heroin use disorder (OR: 1.063, p = 0.804). Thus, the reformulation of OxyContin appears to have reduced prescription pain reliever misuse without contributing to relatively greater new heroin use among those who misused OxyContin prior to the reformulation

Subcutaneous Administration of D-Luciferin is an Effective Alternative to Intraperitoneal Injection in Bioluminescence Imaging of Xenograft Tumors in Nude Mice

Currently, intraperitoneal (IP) injection of D-luciferin is the preferred method of providing substrate for bioluminescence imaging (BLI); however it has a failure rate of 3–10% due to accidental intestinal injection. The present study evaluates the quality of BLI after subcutaneous (SC) injection of D-luciferin and demonstrates the effectiveness of SC injection in anatomically disparate tumor models. Mice bearing luciferase-expressing tumors underwent BLI after SC or IP injection of D-luciferin. The average time to maximal luminescence was 6 min (range 5–9 min) after SC injection and 8 min (range 5–8 min) after IP injection. Within 7 minutes of injection, SC and IP routes yielded similar luminescence in subcutaneous, intracranial, tongue, and lung xenograft tumor models. In a model of combined subcutaneous and intracranial xenografts, SC injection resulted in proportional luminescence at all sites, confirming that preferential delivery of substrate does not occur. While tumors were occasionally not visualized with IP injection, all tumors were visualized reliably with SC injection. Thus, SC injection of D-luciferin is a convenient and effective alternative to IP injection for BLI in nude mice. It may be a preferable approach, particularly for tumors with weaker signals and/or when greater precision is required

The fate of indeterminate liver lesions: What proportion are precursors of hepatocellular carcinoma?

BACKGROUND: The natural history and incidence of hepatocellular carcinoma (HCC) arising from indeterminate liver lesions are not well described. We aimed to define the incidence of HCC in a cohort of patients undergoing surveillance by magnetic resonance imaging (MRI) and estimate any associations with incident HCC. METHODS: We performed a retrospective follow-up study, identifying MRI scans in which indeterminate lesions had been reported between January 2006 and January 2017. Subsequent MRI scan reports were reviewed for incident HCC arising from indeterminate lesions, data were extracted from electronic patient records and survival analysis performed to estimate associations with baseline factors. RESULTS: One hundred and nine patients with indeterminate lesions on MRI were identified. HCC developed in 19 (17%) patients over mean follow up of 4.6 years. Univariate Cox proportional hazards analysis found incident HCC to be significantly associated with baseline low platelet count (hazard ratio (HR) = 7.3 (95% confidence intervals (CI) 2.1-24.9), high serum alpha-fetoprotein level (HR = 2.7 (95% CI 1.0-7.1)) and alcohol consumption above fourteen units weekly (HR = 3.1 (95% CI 1.1-8.7)). Multivariate analysis, however, found that only low platelet count was independently associated with HCC (HR = 5.5 (95% CI 0.6-5.1)). CONCLUSIONS: HCC arises in approximately one fifth of indeterminate liver lesions over 4.6 years and is associated with a low platelet count at the time of first diagnosis of an indeterminate lesion. Incidence of HCC was more common in people with viral hepatitis and in those consuming > 14 units of alcohol per week. Our data may be used to support a strategy of enhanced surveillance in patients with indeterminate lesions

Endothelial cell activation, reduced endothelial cell reparative capacity, and impaired endothelial-dependent vasodilation after anger provocation

The experience of anger increases the acute and long-term risks of incident cardiovascular disease (CVD) events [1] and [2]. The mechanism(s) whereby anger is associated with increased CVD risk remains to be fully characterized. One promising candidate mechanism is endothelial dysfunction. Endothelial dysfunction, as evidenced by impaired endothelial-dependent vasodilation, is an early pathogenic process underlying atherosclerosis development and CVD onset. More recent investigations have elucidated the cellular pathways underlying endothelial dysfunction. Endothelial cell (EC) injury can be assessed by measuring circulating levels of EC-derived microparticles (EMPs), which are phospholipid rich, submicron particles derived and released from the membranes of activated or apoptotic ECs [3]. In addition, the discovery of circulating, bone marrow-derived endothelial progenitor cells (EPCs) capable of EC repair and regeneration [4] suggests that endothelial function represents a balance between ongoing injury and repair. We previously reported that anger provocation acutely impairs arterial vasomotion in apparently healthy individuals [5]. We conducted a study to examine the acute effects of anger provocation not only on arterial vasodilation but also on levels of EMPs and bone marrow-derived EPCs. To our knowledge, this is the first report concerning the adverse effects of anger provocation on cellular pathways underlying EC health