Cost-Effectiveness of Newborn Circumcision in Reducing Lifetime HIV Risk among U.S. Males

BACKGROUND: HIV incidence was substantially lower among circumcised versus uncircumcised heterosexual African men in three clinical trials. Based on those findings, we modeled the potential effect of newborn male circumcision on a U.S. male's lifetime risk of HIV, including associated costs and quality-adjusted life-years saved. METHODOLOGY/PRINCIPAL FINDINGS: Given published estimates of U.S. males' lifetime HIV risk, we calculated the fraction of lifetime risk attributable to heterosexual behavior from 2005-2006 HIV surveillance data. We assumed 60% efficacy of circumcision in reducing heterosexually-acquired HIV over a lifetime, and varied efficacy in sensitivity analyses. We calculated differences in lifetime HIV risk, expected HIV treatment costs and quality-adjusted life years (QALYs) among circumcised versus uncircumcised males. The main outcome measure was cost per HIV-related QALY saved. Circumcision reduced the lifetime HIV risk among all males by 15.7% in the base case analysis, ranging from 7.9% for white males to 20.9% for black males. Newborn circumcision was a cost-saving HIV prevention intervention for all, black and Hispanic males. The net cost of newborn circumcision per QALY saved was $87,792 for white males. Results were most sensitive to the discount rate, and circumcision efficacy and cost. CONCLUSIONS/SIGNIFICANCE: Newborn circumcision resulted in lower expected HIV-related treatment costs and a slight increase in QALYs. It reduced the 1.87% lifetime risk of HIV among all males by about 16%. The effect varied substantially by race and ethnicity. Racial and ethnic groups who could benefit the most from circumcision may have least access to it due to insurance coverage and state Medicaid policies, and these financial barriers should be addressed. More data on the long-term protective effect of circumcision on heterosexual males as well as on its efficacy in preventing HIV among MSM would be useful

Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Hemoglobinopathies Using a Reduced-Intensity Conditioning Regimen and Third-Party Mesenchymal Stromal Cells

AbstractAllogeneic hematopoietic stem cell transplantation for patients with a hemoglobinopathy can be curative but is limited by donor availability. Although positive results are frequently observed in those with an HLA-matched sibling donor, use of unrelated donors has been complicated by poor engraftment, excessive regimen-related toxicity, and graft-versus-host disease (GVHD). As a potential strategy to address these obstacles, a pilot study was designed that incorporated both a reduced-intensity conditioning and mesenchymal stromal cells (MSCs). Six patients were enrolled, including 4 with high-risk sickle cell disease (SCD) and 2 with transfusion-dependent thalassemia major. Conditioning consisted of fludarabine (150 mg/m2), melphalan (140 mg/m2), and alemtuzumab (60 mg for patients weighing > 30 kg and .9 mg/kg for patients weighing <30 kg). Two patients received HLA 7/8 allele matched bone marrow and 4 received 4-5/6 HLA matched umbilical cord blood as the source of HSCs. MSCs were of bone marrow origin and derived from a parent in 1 patient and from an unrelated third-party donor in the remaining 5 patients. GVHD prophylaxis consisted of cyclosporine A and mycophenolate mofetil. One patient had neutropenic graft failure, 2 had autologous hematopoietic recovery, and 3 had hematopoietic recovery with complete chimerism. The 2 SCD patients with autologous hematopoietic recovery are alive. The remaining 4 died either from opportunistic infection, GVHD, or intracranial hemorrhage. Although no infusion-related toxicity was seen, the cotransplantation of MSCs was not sufficient for reliable engraftment in patients with advanced hemoglobinopathy. Although poor engraftment has been observed in nearly all such trials to date in this patient population, there was no evidence to suggest that MSCs had any positive impact on engraftment. Because of the lack of improved engraftment and unacceptably high transplant-related mortality, the study was prematurely terminated. Further investigations into understanding the mechanisms of graft resistance and development of strategies to overcome this barrier are needed to move this field forward

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Cost-Effectiveness of Pooled Nucleic Acid Amplification Testing for Acute HIV Infection after Third-Generation HIV Antibody Screening and Rapid Testing in the United States: A Comparison of Three Public Health Settings

Angela Hutchinson and colleagues conducted a cost-effectiveness analysis of pooled nucleic acid amplification testing following HIV testing and show that it is not cost-effective at recommended antibody testing intervals for high-risk persons except in very high-incidence settings

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Food venue choice, consumer food environment, but not food venue availability within daily travel patterns are associated with dietary intake among adults, Lexington Kentucky 2011

Objective The retail food environment may be one important determinant of dietary intake. However, limited research focuses on individuals’ food shopping behavior and activity within the retail food environment. This study’s aims were to determine the association between six various dietary indicators and 1) food venue availability; 2) food venue choice and frequency; and 3) availability of healthy food within food venue. Methods In Fall, 2011, a cross-sectional survey was conducted among adults (n=121) age 18 years and over in Lexington, Kentucky. Participants wore a global position system (GPS) data logger for 3-days (2 weekdays and 1 weekend day) to track their daily activity space, which was used to assess food activity space. They completed a survey to assess demographics, food shopping behaviors, and dietary outcomes. Food store audits were conducted using the Nutrition Environment Measurement Survey-Store Rudd (NEMS-S) in stores where respondents reported purchasing food (n=22). Multivariate logistic regression was used to examine associations between six dietary variables with food venue availability within activity space; food venue choice; frequency of shopping; and availability of food within food venue. Results 1) Food venue availability within activity space – no significant associations. 2) Food Venue Choice – Shopping at farmers’ markets or specialty grocery stores reported higher odds of consuming fruits and vegetables (OR 1.60 95% CI [1.21, 2.79]). Frequency of shopping - Shopping at a farmers’ markets and specialty stores at least once a week reported higher odds of consumption of fruits and vegetables (OR 1.55 95% CI [1.08, 2.23]). Yet, shopping frequently at a super market had higher odds of consuming sugar-sweetened beverages (OR 1.39 95% CI [1.03, 1.86]). 3) Availability of food within store – those who shop in supermarkets with high availability of healthy food has lower odds of consuming sugar-sweetened beverages (OR 0.65 95% CI [0.14, 0.83]). Conclusion Interventions aimed at improving fruit and vegetable intake need to consider where individuals’ purchase food and the availability within stores as a behavioral and environmental strategy