Safety and Adherence to Intermittent Pre-Exposure Prophylaxis (PrEP) for HIV-1 in African Men Who Have Sex with Men and Female Sex Workers

Background Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). Methods/Principal Findings MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a onemonth recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63–92] for daily dosing and 55% [IQR:28–78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14–50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. Conclusions/Significance Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens</p

A comparison of four fibrosis indexes in chronic HCV: Development of new fibrosis-cirrhosis index (FCI)

<p>Abstract</p> <p>Background</p> <p>Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers.</p> <p>Methods</p> <p>We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)].</p> <p>Results</p> <p>Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%.</p> <p>Conclusions</p> <p>The fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.</p

Alternative Interleukin 17A/F Locus Haplotypes Are Associated With Increased Risk to Hip and Knee Osteoarthritis

We studied the genetic epidemiology of primary large‐joint (hip and knee) osteoarthritis (OA), in order to find disease risk factors by a candidate‐gene approach. We used case–control study in the Croatian Caucasian population. We genotyped 500 OA patients (260 hip, 240 knee; both with total joint replacements) and 597 healthy individuals for single‐nucleotide polymorphisms (SNPs) in interleukin 17A (IL17A) (rs2275913) and IL17F (rs763780 and rs1889570) genes. On the basis of our population and allelic and genotypic frequencies haplotypes were predicted by PHASE software and compared between patients and controls. The three‐SNP haplotype (rs2275913–rs763780–rs1889570) G–C–A confers predisposition to hip (p < 0.005) but not knee OA. The three‐SNP haplotype having opposed nucleotides A–T–G was found significantly associated with 2.6 times higher risk for developing knee (p < 0.02) but not hip OA. The haplotype G–T (IL17A–IL17F; rs2275913–rs763780) is associated with protection to the disease in hip OA (p < 0.01). Our analyses show that two disparate haplotypes within the IL17A‐F gene locus are associated with higher risk to developing hip and knee OA in the Croatian population. The data might suggest a difference in the etiology of hip OA from that of the knee OA, perhaps due to an unknown dissimilarity in vulnerability of these joints to the actions of IL17. Alternatively, other differences in genetic factors like the long non‐ protein coding region LINCMD1 and/or microRNA species like miR133b and miR206 found in the vicinity of the IL17 locus might be involved in the observed risk

Beliefs and Expectations of Women Under 50 Years Old Regarding Screening Mammography: A Qualitative Study

OBJECTIVE: Because shared decision making has been recommended for screening mammography by women under age 50, we studied women's decision-making process regarding the procedure. DESIGN: Qualitative research design using in-depth semi-structured interviews. PATIENTS: Sixteen white and African-American women aged 38 to 45 receiving care at a large New England medical practice. MEASUREMENTS AND MAIN RESULTS: We identified the following content areas in women's decision-making process: intentions for screening, motivating factors to undergo screening, attitudes toward screening mammography, attitudes toward breast cancer, and preferences for information and shared decision making. In our sample, all women had or intended to have a screening mammogram before age 50. They were motivated by the awareness of the recommendation to begin screening at age 40, knowing others with breast cancer, and a sense of personal responsibility for their health. Participants feared breast cancer and thought the benefits of screening mammography far outweighed its risks. Women's preferences for involvement in decision making varied from wanting full responsibility for screening decisions to deferring to their medical providers. All preferred the primary care provider to be the main source of information, yet the participants stated that their own providers played a limited role in educating them about the risks and benefits of screening and the mammography procedure itself. Most of their information was derived from the media. CONCLUSIONS: The women in this study demonstrated little ambivalence in their desire for mammography screening prior to age 50. They reported minimal communication with their medical providers about the risks and benefits of screening. Better information flow regarding mammography screening is necessary. Given the lack of uncertainty among women's perceptions regarding screening mammography, shared decision making in this area may be difficult to achieve

TBL1Y: a new gene involved in syndromic hearing loss

Hereditary hearing loss (HHL) is an extremely heterogeneous disorder with autosomal dominant, recessive, and X-linked forms. Here, we described an Italian pedigree affected by HHL but also prostate hyperplasia and increased ratio of the free/total PSA levels, with the unusual and extremely rare Y-linked pattern of inheritance. Using exome sequencing we found a missense variant (r.206A>T leading to p.Asp69Val) in the TBL1Y gene. TBL1Y is homologous of TBL1X, whose partial deletion has described to be involved in X-linked hearing loss. Here, we demonstrate that it has a restricted expression in adult human cochlea and prostate and the variant identified induces a lower protein stability caused by misfolded mutated protein that impairs its cellular function. These findings indicate that TBL1Y could be considered a novel candidate for HHL