Association between the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) rs4073366 polymorphism and ovarian hyperstimulation syndrome during controlled ovarian hyperstimulation

Background The aim of this study was to determine the relationship between a purported luteinizing hormone/chorionic gonadotropin (LHCGR) high function polymorphism (rs4539842/insLQ) and outcome to controlled ovarian hyperstimulation (COH). Methods This was a prospective study of 172 patients undergoing COH at the Fertility and IVF Center at GWU. DNA was isolated from blood samples and a region encompassing the insLQ polymorphism was sequenced. We also investigated a polymorphism (rs4073366 G \u3e C) that was 142 bp frominsLQ. The association of the insLQ and rs4073366 alleles and outcome to COH (number of mature follicles, estradiol level on day of human chorionic gonadotropin (hCG) administration, the number of eggs retrieved and ovarian hyperstimulation syndrome (OHSS)) was determined. Results Increasing age and higher day 3 (basal) FSH levels were significantly associated with poorer response to COH. We found that both insLQ and rs4073366 were in linkage disequilibrium (LD) and no patients were homozygous for both recessive alleles (insLQ/insLQ; C/C). The insLQ variant was not significantly associated with any of the main outcomes to COH. Carrier status for the rs4073366 C variant was associated (P = 0.033) with an increased risk (OR 2.95, 95% CI = 1.09-7.96) of developing OHSS. Conclusions While age and day 3 FSH levels were predictive of outcome, we found no association betweeninsLQ and patient response to COH. Interestingly, rs4073366 C variant carrier status was associated with OHSS risk. To the best of our knowledge, this is the first report suggesting thatLHCGR genetic variation might function in patient risk for OHSS

Use of National Standards to Monitor HIV Care and Treatment in a High Prevalence City-Washington, DC.

We sought to benchmark the quality of HIV care being received by persons living with HIV in care in Washington, DC and identify individual-level and structural-level differences. Data from the DC Cohort, an observational HIV cohort of persons receiving outpatient care in DC, were used to estimate the Institute of Medicine (IOM) and Department of Health and Human Services (HHS) quality of care measures. Differences in care by demographics and clinic type were assessed using χ2 tests and multivariable regression models. Among 8,047 participants, by HHS standards, 69% of participants were retained in care (RIC), 95% were prescribed antiretroviral therapy (ART), and 84% were virally suppressed (VS). By IOM standards, 84% were in continuous care; and 78% and 80% underwent regular CD4 and VL monitoring, respectively. Screening for syphilis, chlamydia, and gonorrhea was 51%, 31%, and 26%, respectively. Older participants were 1.5 times more likely to be RIC compared to younger participants (OR: 1.5; 95% CI: 1.3, 1.8). Participants enrolled in community-based clinics were more likely to be RIC (OR: 1.7; 95% CI: 1.4, 2.0) versus those enrolled at hospital-based clinics. Older participants were more likely to achieve VS than younger participants (OR: 1.8; 95% CI: 1.5, 2.2) while Black participants were less likely compared to white participants (OR: 0.4; 95% CI: 0.3, 0.5). Despite high measures of quality of care, disparities remain. Continued monitoring of the quality of HIV care and treatment can inform the development of public health programs and interventions to optimize care delivery

Ibudilast attenuates peripheral inflammatory effects of methamphetamine in patients with methamphetamine use disorder.

BackgroundPreclinical studies suggest that the non-selective phosphodiesterase inhibitor, Ibudilast (IBUD) may contribute to the treatment of methamphetamine (METH) use disorder through the attenuation of METH-induced inflammatory markers such as adhesion molecules, sICAM-1 and sVCAM-1, and cytokines, IL-6 and TNF-α.ObjectiveThe present study aimed to test whether treatment with IBUD can attenuate peripheral markers of inflammation during a METH challenge in an inpatient clinical trial of 11 patients.MethodsThis trial followed a randomized, within-subjects crossover design where participants received a METH challenge, during which five participants were treated with placebo then with IBUD, while the remaining six participants were treated with IBUD prior to placebo. Mixed effects regression modeled changes in peripheral markers of inflammation-sICAM-1, sVCAM-1, TNF-α, IL-6, MIF, and cathepsin D-by treatment condition, with measurements at baseline, 60 min post-METH infusion, and 360 min post-METH infusion.ResultsWhile on placebo, sICAM-1, sVCAM-1, and cathepsin D significantly increased by 60 min post-METH infusion, while IL-6 significantly increased 360 min post-METH infusion. Treatment with IBUD significantly reduced METH-induced levels of sICAM-1, sVCAM-1, and cathepsin D at 60 min post-METH infusion.ConclusionsOur findings demonstrate that IBUD attenuated acute pro-inflammatory effects of METH administration, which may have implications for treatment of METH use disorder

Voting with their feet: Social factors linked with treatment for opioid use disorder using same-day buprenorphine delivered in California hospitals.

BackgroundMedication for opioid use disorder (MOUD) using buprenorphine in primary or specialty care settings is accessed primarily by persons with private health insurance, stable housing, and no polysubstance use. This paper applies Social Cognitive Theory to frame links between social factors and treatment outcomes among patients with social and economic disadvantages who are seeking MOUD at California Bridge Program (CA Bridge) hospitals.MethodsElectronic medical records for patients identified with OUD between January-April, 2020 receiving care at CA Bridge hospitals defined outcomes: hospital-administered buprenorphine; provision of buprenorphine prescription at discharge. Multi-level models assessed whether social factors-housing status, insurance type, and co-methamphetamine use-predicted outcomes while accounting for group-level effects of treating hospital and controlling for age, race/ethnicity, and gender.Results15 CA Bridge hospitals yielded 845 patient records. Most patients received hospital-administered buprenorphine (58 %) and/or a buprenorphine prescription (55 %); 26 % received neither treatment. Patients with unstable housing had greater odds of hospital-administered buprenorphine compared to patients with stable housing. Patients with Medicaid had greater odds of receiving a buprenorphine prescription compared to patients with other insurance. Co-methamphetamine use was not associated with outcomes.ConclusionsPatients with OUD are successful in accessing same-day MOUD in CA Bridge hospital settings over a significant period. Importantly, access to MOUD in these settings was facilitated for patients traditionally not treated using buprenorphine, i.e., those with housing instability, Medicaid insurance, and co-methamphetamine use. Findings suggest barriers to MOUD for patients with social and economic disadvantages can be lowered by changing treatment delivery

Social Genomics of Methamphetamine Use, HIV Viral Load, and Social Adversity

BackgroundSocial genomics has demonstrated altered inflammatory and type I interferon (IFN) gene expression among people experiencing chronic social adversity. Adverse social experiences such as discrimination and violence are linked to stimulant misuse and HIV, conditions that dysregulate inflammatory and innate antiviral responses, leading to increased HIV viral replication and risk of chronic diseases.PurposeWe aimed to determine whether methamphetamine (MA) use, unsuppressed HIV viral load (VL) (≥200 c/mL), and experienced intimate partner violence (IPV) (past 12 months) predicted inflammatory and type I IFN gene expression in HIV-positive Black and Latinx men who have sex with men (MSM).MethodsParticipants were 147 HIV-positive Black and Latinx MSM recruited from the mSTUDY, a cohort of 561 MSM aged 18-45 in Los Angeles, CA, of whom half are HIV-positive and substance-using. Transcriptomic measures of inflammatory and type I IFN activity were derived from RNA sequencing of peripheral blood mononuclear cells and matched to urine drug tests, VL, and survey data across two time points 12 months apart. Analysis used linear random intercept modeling of MA use, unsuppressed VL, and experienced IPV on inflammatory and type I IFN expression.ResultsIn adjusted models, MA use predicted 27% upregulated inflammatory and 31% upregulated type I IFN expression; unsuppressed VL predicted 84% upregulated type I IFN but not inflammatory expression; and experienced IPV predicted 31% upregulated inflammatory and 26% upregulated type I IFN expression.ConclusionsIn Black and Latinx MSM with HIV, MA use, unsuppressed VL, and experienced IPV predicted upregulated social genomic markers of immune functioning

Development of a large urban longitudinal HIV clinical cohort using a web-based platform to merge electronically and manually abstracted data from disparate medical record systems: technical challenges and innovative solutions.

Objective Electronic medical records (EMRs) are being increasingly utilized to conduct clinical and epidemiologic research in numerous fields. To monitor and improve care of HIV-infected patients in Washington, DC, one of the most severely affected urban areas in the United States, we developed a city-wide database across 13 clinical sites using electronic data abstraction and manual data entry from EMRs. Materials and Methods To develop this unique longitudinal cohort, a web-based electronic data capture system (Discovere®) was used. An Agile software development methodology was implemented across multiple EMR platforms. Clinical informatics staff worked with information technology specialists from each site to abstract data electronically from each respective site’s EMR through an extract, transform, and load process. Results Since enrollment began in 2011, more than 7000 patients have been enrolled, with longitudinal clinical data available on all patients. Data sets are produced for scientific analyses on a quarterly basis, and benchmarking reports are generated semi-annually enabling each site to compare their participants’ clinical status, treatments, and outcomes to the aggregated summaries from all other sites. Discussion Numerous technical challenges were identified and innovative solutions developed to ensure the successful implementation of the DC Cohort. Central to the success of this project was the broad collaboration established between government, academia, clinics, community, information technology staff, and the patients themselves. Conclusions Our experiences may have practical implications for researchers who seek to merge data from diverse clinical databases, and are applicable to the study of health-related issues beyond HIV

Proportion of DC cohort participants meeting criteria for selected HHS and IOM indicators for quality of care, DC cohort, 2011–2016.

<p>This figure represents individuals who were enrolled in the DC Cohort as of September 30, 2016 and met the criteria for selected Department of Health and Human Services and Institute of Medicine HIV quality of care indicators. While high proportions of participants met the HIV-related indicators (69%-95%), screening for sexually transmitted infections was relatively low (26%-51%).</p

Factors associated with select IOM-defined care indicators, DC Cohort, 2011–2016^a^,^b^,^c.

<p>Factors associated with select IOM-defined care indicators, DC Cohort, 2011–2016<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186036#t004fn001" target="_blank">^a</a>^,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186036#t004fn002" target="_blank">^b</a>^,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186036#t004fn003" target="_blank">^c</a>.</p