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BACKGROUNDApproximately 15% of HIV-infected men who have sex with men (MSM) engaged in HIV primary care have been diagnosed as having a sexually transmitted infection (STI) in the past year, yet STI testing frequency remains low. METHODSWe sought to quantify STI testing frequencies at a large, urban HIV care clinic, and to identify patient- and provider-related barriers to increased STI testing. We extracted laboratory data in aggregate from the electronic medical record to calculate STI testing frequencies (defined as the number of HIV-infected MSM engaged in care who were tested at least once over an 18-month period divided by the number of MSM engaged in care). We created anonymous surveys of patients and providers to elicit barriers. RESULTSExtragenital gonorrhea and chlamydia testing was low (29%–32%), but the frequency of syphilis testing was higher (72%). Patients frequently reported high-risk behaviors, including drug use (16.4%) and recent bacterial STI (25.5%), as well as substantial rates of recent testing (>60% in prior 6 months). Most (72%) reported testing for STI in HIV primary care, but one-third went elsewhere for “easier” (42%), anonymous (21%), or more frequent (16%) testing. HIV primary care providers lacked testing and treatment knowledge (25%–32%) and cited lack of time (68%), discomfort with sexual history taking and genital examination (21%), and patient reluctance (39%) as barriers to increased STI testing. CONCLUSIONSexually transmitted infection testing in HIV care remains unacceptably low. Enhanced education of providers, along with strategies to decrease provider time and increase patient ease and frequency of STI testing, is needed.

Although many rare variants have been reportedly associated with Parkinson’s disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants. We assessed a total of 27,590 PD cases, 6701 PD proxies, and 3,106,080 controls from three data sets: 23andMe, Inc., UK Biobank, and AMP-PD. Based on well-known PD genes, 834 variants of interest were selected from the ClinVar annotated 23andMe dataset. We performed a meta-analysis using summary statistics of all three studies. The meta-analysis resulted in five significant variants after Bonferroni correction, including variants in GBA1 and LRRK2 . Another eight variants are strong candidate variants for their association with PD. Here, we provide the largest rare variant meta-analysis to date, providing information on confirmed and newly identified variants for their association with PD using several large databases. Additionally we also show the complexities of studying rare variants in large-scale cohorts.

Objective To examine the associations of LRRK2 p.G2019S, GBA1 p.N409S, polygenic risk scores (PRS), and APOE E4 on PD penetrance, risk, and symptoms. Methods We conducted a US‐based observational case–control study using data from the 23andMe Inc. and Fox Insight Genetic Substudy (FIGS) databases. The total cohort included 7,586,842 participants (n = 35,163 PD); 8791 LRRK2 p.G2019S carriers (565 with PD), 37,427 GBA1 p.N409S carriers (524 with PD), 244 dual LRRK2/GBA1 carriers (37 with PD), and 7.5 million noncarriers (34,037 with PD). PRS was calculated from the most recently published European genome‐wide association study. Survival models estimated the cumulative incidence of PD. Logistic regressions estimated the relative odds of reporting motor and non‐motor symptoms according to genetic exposure. Results By the age of 80 years, the cumulative incidence of PD was 30% for dual carriers, 24% for LRRK2 p.G2019S carriers, 4% for GBA1 p.N409S carriers, and 2% for noncarriers. Higher PRS was associated with increased penetrance of the variants and earlier time to PD diagnosis. GBA1 p.N409S PD was associated with the highest burden of non‐motor symptoms, including REM sleep behavior disorder and cognitive/memory deficits, and LRRK2 p.G2019S with the lowest. APOE E4 dosage was associated with greater odds of reporting hallucinations and cognitive impairment in addition to carrier status. Interpretation Our findings support the use of genetic screening to enrich candidate selection for neuroprotective trials and better define outcome measures based on genetics.

Dyslexia is a learning difficulty with neurodevelopmental origins, manifesting as reduced accuracy and speed in reading and spelling. It is substantially heritable and frequently co-occurs with other neurodevelopmental conditions, particularly attention deficit-hyperactivity disorder (ADHD). Here, we investigate the genetic structure underlying dyslexia and a range of psychiatric traits using results from genome-wide association studies of dyslexia, ADHD, autism, anorexia nervosa, anxiety, bipolar disorder, major depressive disorder, obsessive compulsive disorder, schizophrenia, and Tourette syndrome. Genomic Structural Equation Modelling (GenomicSEM) showed heightened support for a model consisting of five correlated latent genomic factors described as: F1) compulsive disorders (including obsessive-compulsive disorder, anorexia nervosa, Tourette syndrome), F2) psychotic disorders (including bipolar disorder, schizophrenia), F3) internalising disorders (including anxiety disorder, major depressive disorder), F4) neurodevelopmental traits (including autism, ADHD), and F5) attention and learning difficulties (including ADHD, dyslexia). ADHD loaded more strongly on the attention and learning difficulties latent factor (F5) than on the neurodevelopmental traits latent factor (F4). The attention and learning difficulties latent factor (F5) was positively correlated with internalising disorders (.40), neurodevelopmental traits (.25) and psychotic disorders (.17) latent factors, and negatively correlated with the compulsive disorders (–.16) latent factor. These factor correlations are mirrored in genetic correlations observed between the attention and learning difficulties latent factor and other cognitive, psychological and wellbeing traits. We further investigated genetic variants underlying both dyslexia and ADHD, which implicated 49 loci (40 not previously found in GWAS of the individual traits) mapping to 174 genes (121 not found in GWAS of individual traits) as potential pleiotropic variants. Our study confirms the increased genetic relation between dyslexia and ADHD versus other psychiatric traits and uncovers novel pleiotropic variants affecting both traits. In future, analyses including additional co-occurring traits such as dyscalculia and dyspraxia will allow a clearer definition of the attention and learning difficulties latent factor, yielding further insights into factor structure and pleiotropic effects.

BACKGROUNDSexually transmitted infections (STIs) disproportionately affect men who have sex with men. Although clinical practice guidelines recommend routine STI screening of men who have sex with men who have high-risk behaviors, extragenital STI testing rates have been low in HIV clinics across the nation. The University of Washington STD Prevention Training Center implemented an STI self-testing program at a large HIV primary care clinic in Seattle, WA, to facilitate extragenital STI testing. METHODSWe performed a mixed-methods program evaluation to assess health care provider acceptability of the program at 9 months after implementation. Twenty-eight clinicians were invited to complete an online survey. We conducted one-on-one, semistructured interviews with 6 clinicians and a focus group with 7 members of the clinic nursing staff. Survey responses were tallied. Conventional content analysis was performed on survey comments and transcripts from the interviews and focus group. RESULTSNinety-one percent of clinicians were either satisfied or very satisfied with the program. Perceived advantages of the program included saving time for clinicians, overcoming patient discomfort, and increasing patient access to testing. Perceived program disadvantages included unclear responsibility of directing patients through the self-testing process and incorrect sample collection and labeling. CONCLUSIONSDespite perceived disadvantages, the self-testing program was acceptable to clinicians and nursing staff, key population for successful program adoption. Implementation of STI self-testing programs in clinic settings could help to increase extragenital STI testing rates by removing provider and patient barriers to testing.

Although the physical and emotional impact of surgical removal of partial or complete removal of the breast as well as effects of breast cancer treatment on the individual have been well documented, little research is available on sexuality and sexual health of breast cancer survivors in a relationship context. Sexual health concerns of breast cancer survivors remain an unmet need for many. The present study consisted of qualitative interviews with 135 racially diverse, female breast cancer survivors who completed treatment to better understand their perspectives on sexual health and management of sexual problems in their potential and existing relationships after breast cancer. Key thematic findings include that breast cancer survivors have to (1) adapt to the physical and emotional traumas of breast cancer surgery and treatment, (2) navigate complicated sexual communications with potential and existing partners, and (3) negotiate intimacy and closeness without sexual intercourse with existing partners. This study demonstrates the need for healthcare providers to discuss sexual health after breast cancer with all of their patients as it is a concern that faces single and partnered breast cancer survivors months and years after treatment.

Background Polygenic risk scores (PRS) estimate an individual’s germline genetic predisposition to a quantitative trait and/or risk of disease. Several PRS have been developed for cancer risk with the goal of improved risk screening. Here, we sought to establish whether PRS for cancer risk and other common traits may influence survival for patients with cancer. Methods We conducted a PRS survival analysis using 23,770 cancer patients of European ancestry from the Dana-Farber Cancer Institute Profile cohort. Results We identified an association between PRS for breast cancer risk and longer patient survival (HR = 0.89 (95% CI: 0.84–0.95), p  = 1.50 × 10 –4 , < 5% FDR), implying that individuals at high genetic risk had better outcomes. High PRS individuals were also significantly less likely to harbor somatic TP53 mutations, consistent with having less aggressive tumors. This association persisted when including tumor grade and became more protective when restricting to ER-negative tumors (HR = 0.78 (95% CI: 0.68–0.89), p  = 1.69 × 10 –4 ). Potential confounders such as hormone receptor status, age, grade, stage, and ER-targeted therapy did not fully explain this association, nor was there statistical evidence of index event bias at individual variants. We did not observe significant associations between cancer risk and survival for other cancers, suggesting that this mechanism may be largely unique to breast cancer. However, we did observe associations between shorter survival and type 2 diabetes, bipolar, and pancreatitis PRS (1% FDR). Conclusions These findings suggest that higher germline risk may predispose individuals to less aggressive breast cancer tumors and provide novel insights into breast cancer development and prognosis.

Dog ownership has been associated with several complex traits, and there is evidence of genetic influence. We performed a genome-wide association study of dog ownership through a meta-analysis of 31,566 Swedish twins in 5 discovery cohorts and an additional 65,986 European-ancestry individuals in 3 replication cohorts from Sweden, Norway, and the United Kingdom. Association tests with >7.4 million single-nucleotide polymorphisms were meta-analyzed using a fixed effect model after controlling for population structure and relatedness. We identified 2 suggestive loci using discovery cohorts, which did not reach genome-wide significance after meta-analysis with replication cohorts. Single-nucleotide polymorphism-based heritability of dog ownership using linkage disequilibrium score regression was estimated at 0.123 (CI 0.038–0.207) using the discovery cohorts and 0.018 (CI −0.002 to 0.039) when adding in replication cohorts. Negative genetic correlation with complex traits including type 2 diabetes, depression, neuroticism, and asthma was only found using discovery summary data. Furthermore, we did not identify any genes/gene-sets reaching even a suggestive level of significance. This genome-wide association study does not, by itself, provide clear evidence on common genetic variants that influence dog ownership among European-ancestry individuals.