High Rates of Missed HIV Testing Among Oral PrEP Users in the United States From 2018-2021: A National Assessment on Compliance With HIV Testing Recommendations of the CDC PrEP Guidelines.

Background: The US Centers for Disease Control and Prevention recommends HIV testing every 3 months in oral PrEP users. We performed a national assessment of HIV testing compliance among oral PrEP users. Methods: We analyzed 408 910 PrEP prescriptions issued to 39 809 PrEP users using a national insurance claims database that contained commercial and Medicaid claims. We identified PrEP use based on pharmacy claims and outpatient diagnostic coding. We evaluated the percentage of PrEP prescription refills without HIV testing (identified by CPT codes) within the prior 3, 6, and 12 months using time to event methods. We performed subgroup and multivariate analyses by age, gender, race, insurance type, and geography. Results: Of 39 809 persons, 36 197 were commercially insured, 3612 were Medicaid-insured, and 96% identified as male; the median age (interquartile range) was 34 (29-44) years, and the Medicaid-insured PrEP users were 24% Black/African American, 44% White, and 9% Hispanic/Latinx. Within the prior 3, 6, and 12 months, respectively, the percentage of PrEP prescription fills in individuals without HIV Ag/Ab testing was 34.3% (95% CI, 34.2%-34.5%), 23.8% (95% CI, 23.7%-23.9%), and 16.6% (95% CI, 16.4%-16.7%), and the percentage without any type of HIV test was 25.8% (95% CI, 25.6%-25.9%), 14.6% (95% CI, 14.5%-14.7%), and 7.8% (95% CI, 7.7%-7.9%). Conclusions: Approximately 1 in 3 oral PrEP prescriptions were filled in persons who had not received an HIV Ag/Ab test within the prior 3 months, with evidence of health disparities. These findings inform clinical PrEP monitoring efforts and compliance with national HIV testing guidance to monitor PrEP users.

Dichotomous regulation of striatal plasticity by dynorphin.

Modulation of corticostriatal plasticity alters the information flow throughout basal ganglia circuits and represents a fundamental mechanism for motor learning, action selection, and reward. Synaptic plasticity in the striatal direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) is regulated by two distinct networks of GPCR signaling cascades. While it is well-known that dopamine D2 and adenosine A2a receptors bi-directionally regulate iSPN plasticity, it remains unclear how D1 signaling modulation of synaptic plasticity is counteracted by dSPN-specific Gi signaling. Here, we show that striatal dynorphin selectively suppresses long-term potentiation (LTP) through Kappa Opioid Receptor (KOR) signaling in dSPNs. Both KOR antagonism and conditional deletion of dynorphin in dSPNs enhance LTP counterbalancing with different levels of D1 receptor activation. Behaviorally, mice lacking dynorphin in D1 neurons show comparable motor behavior and reward-based learning, but enhanced flexibility during reversal learning. These findings support a model in which D1R and KOR signaling bi-directionally modulate synaptic plasticity and behavior in the direct pathway.

Factors associated with suboptimal retention in HIV pre-exposure prophylaxis care among men who have sex with men.

Despite the efficacy of HIV pre-exposure prophylaxis (PrEP), retention in care in the United States remains suboptimal. The goal of this study was to explore factors that lead to suboptimal retention in PrEP care for men who have sex with men (MSM) in real-world clinical settings in the United States. Trained interviewers conducted semi-structured interviews with MSM (N = 49) from three clinics who had been engaged in PrEP care in the Midwest (n = 15), South (n = 15), and Northeast (n = 19) geographic regions and had experienced a lapse in PrEP use. Factors that emerged as related to suboptimal retention in PrEP care included structural factors such as transportation and out-of-pocket costs; social factors such as misinformation on media and in personal networks; clinical factors such as frequency and timing of appointments; and behavioral factors such as changes in sexual behavior and low perceived risk for HIV. Participants suggested reducing the out-of-pocket costs of medications and lab visits, having flexible appointment times, culturally responsive services, and comprehensive patient navigation to help retention in care. These findings leveraged real-world experiences and opinions of patients to inform gaps in current services and how to make changes to optimize PrEP care.

Incidence, Risk Factors, and Outcomes of Acute Kidney Injury in Preterm Neonates Hospitalized in the Neonatology Unit, North India: A Single-center Experience.

Acute kidney injury (AKI) is common in premature newborns and is associated with high mortality. It is unclear which risk factors lead to AKI in these neonates. We aimed to determine the incidence, risk factors, and outcomes of AKI in preterm neonates in the neonatal intensive care unit (NICU). They were screened and staged for AKI as per the amended neonatal criteria of Kidney Disease Improving Global Outcomes and followed up until discharge or death. Serum creatinine levels and urine output were measured. The incidence of AKI was 18.5% (37/200 neonates). The majority developed non-oliguric AKI. The risk factors significantly associated with AKI in neonates were the presence of sepsis, birth asphyxia, shock, respiratory distress syndrome, and hypothermia. The majority of neonates with AKI had a birthweight <1500 g and a gestational age of <32 weeks and had a higher risk of mortality, in contrast to than those without AKI. Mortality and NICU stay were significantly higher among those with Stage 3 AKI compared with Stage 2 and Stage 1 AKI. To prevent AKI and reduce the burden of high mortality in premature neonates, it is essential to prevent sepsis, birth asphyxia, and respiratory distress syndrome, as well as to detect shock and patent ductus arteriosus as early as possible. There is a need for good antenatal care to reduce the burden of prematurity.

Pre-exposure Prophylaxis Discontinuation During the COVID-19 Pandemic Among Men Who Have Sex With Men in a Multisite Clinical Cohort in the United States.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to put strain on health systems in the United States, leading to significant shifts in the delivery of routine clinical services, including those offering HIV pre-exposure prophylaxis (PrEP). We aimed to assess whether individuals discontinued PrEP use at higher rates during the COVID-19 pandemic and the extent to which disruptions to usual clinical care were mitigated through telehealth. METHODS: Using data from an ongoing prospective cohort of men who have sex with men (MSM) newly initiating PrEP in 3 mid-sized cities (n = 195), we calculated the rate of first-time discontinuation of PrEP use in the period before the COVID-19 pandemic and during the COVID-19 pandemic and compared these rates using incidence rate ratios (IRRs). Furthermore, we compared the characteristics of patients who discontinued PrEP use during these periods with those who continued to use PrEP during both periods. RESULTS: Rates of PrEP discontinuation before the COVID pandemic and during the COVID-19 pandemic were comparable [4.29 vs. 5.20 discontinuations per 100 person-months; IRR: 1.95; 95% confidence interval (CI): 0.83 to 1.77]. Although no significant differences in the PrEP discontinuation rate were observed in the overall population, the rate of PrEP discontinuation increased by almost 3-fold among participants aged 18-24 year old (IRR: 2.78; 95% CI: 1.48 to 5.23) and by 29% among participants covered by public insurance plans at enrollment (IRR: 1.29; 95% CI: 1.03 to 5.09). Those who continued to use PrEP were more likely to have had a follow-up clinical visit by telehealth in the early months of the pandemic (45% vs. 17%). CONCLUSIONS: In this study, rates of PrEP discontinuation were largely unchanged with the onset of the COVID-19 pandemic. The use of telehealth likely helped retain patients in PrEP care and should continue to be offered in the future.

Projected Effects of Disruptions to Human Immunodeficiency Virus (HIV) Prevention Services During the Coronavirus Disease 2019 Pandemic Among Black/African American Men Who Have Sex With Men in an Ending the HIV Epidemic Priority Jurisdiction.

Background: Disruptions in access to in-person human immunodeficiency virus (HIV) preventive care during the coronavirus disease 2019 (COVID-19) pandemic may have a negative impact on our progress towards the Ending the HIV Epidemic goals in the United States. Methods: We used an agent-based model to simulate HIV transmission among Black/African American men who have sex with men in Mississippi over 5 years to estimate how different reductions in access affected the number of undiagnosed HIV cases, new pre-exposure prophylaxis (PrEP) starts, and HIV incidence. Results: We found that each additional 25% decrease in HIV testing and PrEP initiation was associated with decrease of 20% in the number of cases diagnosed and 23% in the number of new PrEP starts, leading to a 15% increase in HIV incidence from 2020 to 2022. Conclusions: Unmet need for HIV testing and PrEP prescriptions during the COVID-19 pandemic may temporarily increase HIV incidence in the years immediately after the disruption period.

Preferences for HIV Preexposure Prophylaxis Products Among Black Women in the U.S.

In a nationwide sample of Black women in the U.S., we assessed preferences for HIV preexposure prophylaxis (PrEP) products, including long-acting injectable (LAI) PrEP and once-daily oral PrEP. Among 315 respondents, 32.1% were aware of PrEP and 40.6% were interested in using it; interest increased to 62.2% if PrEP were provided for free. Oral PrEP was the preferred option (51.1%), followed by LAI PrEP (25.7%), vaginal gel (16.5%), and vaginal ring (6.7%). When examining oral and LAI PrEP alone, most (62.7%) preferred oral PrEP. LAI PrEP was more likely to be preferred among respondents with concerns about healthcare costs or PrEP-related stigma, and among those who reported inconsistent condom use and multiple sexual partners. Although most Black women preferred oral PrEP, LAI PrEP may be appealing to a subset with social and structural barriers to PrEP use, such as cost and stigma, and those at increased risk of HIV infection.

Uterine Isthmocele-A Frequently Overlooked Complication of Cesarean Sections.

Uterine isthmocele or uterine niche is a late complication of cesarean deliveries and causes chronic pelvic pain, menorrhagia or postmenstrual spotting, and infertility. As the number of cesarean sections are constantly increasing, it is important to be aware of this entity so as to make an early diagnosis. This would enable the clinicians to manage these patients efficiently. We present three patients of uterine isthmocele who were evaluated and managed at our institution.

Vacuum-Assisted Excision, Scarless Solution for Fibroadenoma Breast-A Single-Center Experience.

Background Fibroadenoma is one of the most common benign breast lesions that is frequently surgically excised in breast practice. Aim The aim of this study was to determine the efficacy and safety of ultrasound-guided (USG) vacuum-assisted excision biopsy (VAEB) of fibroadenoma. Settings and Design A retrospective observational study. Methods and Materials A total of 113 patients with 163 fibroadenomas who underwent USG-guided VAEB under local anesthesia with 7G and 10G probes using an Encor Enspire equipment were included in the study. The patients were followed up after 1, 6, and 12 months. The fibroadenomas up to 4 cm were excised as per the U.S. Food and Drug Administration-approved guidelines of the American Society of Surgeons for percutaneous removal of benign breast lesions. Results The percentage of complete excision rate was 98.8% and the most frequent complication encountered was hematoma including immediate and delayed accounting for 3.06%. There were no recurrent lesions in our study. Conclusion USG-guided VAEB of benign breast lumps can be a safe and effective alternative to surgical excision and had better patient satisfaction in terms of efficacy and cosmesis.

Same-day prescribing of daily oral pre-exposure prophylaxis for HIV prevention.

Pre-exposure prophylaxis (PrEP) is highly effective in reducing HIV transmission but remains underutilised globally. Same-day PrEP prescribing and medication provision is an emerging implementation approach. The experiences of the three same-day PrEP programmes support the feasibility of the approach. Key elements of safe and effective same-day PrEP programmes include the ability to order laboratory tests at the time of the clinical visit and the ability to contact patients when laboratory results are available. Same-day PrEP has the potential to alleviate the attrition seen in usual care between initial evaluation and receipt of a PrEP prescription. A widespread application of same-day prescribing will be needed to assess its effect on PrEP usage.

Associations Among HIV Risk Perception, Sexual Health Efficacy, and Intent to Use PrEP Among Women: An Application of the Risk Perception Attitude Framework.

HIV risk perception is a known determinant of HIV prevention behaviors among vulnerable populations. Lesser known is the combined influence of risk perception and efficacy beliefs on PrEP use. We examined the associations between levels of risk perception and strength of efficacy beliefs on intent to use PrEP in a sample of adult Black and Latina women. Guided by the risk perception attitudes (RPA) framework, we used cluster analysis to identify four interpretable groups. We ran analysis of covariance models to determine the relationship between membership in the RPA framework groups and intention to use PrEP. Among the 908 women, the mean age was 29.9 years and participants were Latina (69.4%) and Black (25.6%). Results of the analysis show that women with low perception of HIV risk and strong efficacy beliefs had significantly less intent to use PrEP than women with high risk perception and weak efficacy beliefs.

Diffusion weighted imaging in breast cancer - Can it be a noninvasive predictor of nuclear grade?

BACKGROUND: DWI and ADC values are noninvasive MRI techniques, which provide quantitative information about tumor heterogeneity. AIM: To determine the minimum and mean ADC values in breast carcinoma and to correlate ADC values with various prognostic factors. SETTINGS AND DESIGN: Prospective observational study. MATERIALS AND METHODS: Fifty-five patients with biopsy-proven breast carcinoma were included in this study. MRI with DWI was performed with Siemens 3T Skyra scanner. ADC values were measured by placing regions of interest (ROIs) within the targeted lesions on ADC maps manually. The histopathological and immunohistochemical analysis of surgical specimen was done to determine the prognostic factors. STATISTICAL ANALYSIS: Students T test and ANOVA were used to study the difference in ADC between two groups. Pearson correlation coefficient was used to quantify the correlation between ADC values and prognostic factors. RESULTS: Lower grade (grade I) breast carcinoma had a significantly high ADC value as compared to higher grade carcinoma (grade II and III). For differentiating Grade I tumors from grade II and III, a minimum ADC cut-off value was 0.79 × 10-3 mm2/sec (83% sensitivity and 84% specificity) and a mean ADC cut-off value was 0.82 × 10-3 mm2/sec (83% sensitivity and 71% specificity) was derived. There was no significant correlation between ADC and other prognostic factors. CONCLUSION: ADC values can be used to differentiate lower grade breast carcinoma (grade I) from higher grades (grade II and III). Minimum ADC values are more accurate in predicting the grade of the breast tumor than mean ADC value.

Validation of the HIV Pre-exposure Prophylaxis Stigma Scale: Performance of Likert and Semantic Differential Scale Versions.

Stigma regarding HIV pre-exposure prophylaxis (PrEP) is commonly implicated as a factor limiting the scale-up of this highly effective HIV prevention modality. To quantify and characterize PrEP stigma, we developed and validated a brief HIV PrEP Stigma Scale (HPSS) among a group of 279 men who have sex with men (MSM). Scale development was informed by a theoretical model to enhance content validity. We assessed two scale versions, Semantic Differential and Likert, randomizing the order in which scales were presented to participants. Both scales demonstrated high internal consistency. The Likert scale had substantially better construct validity and was selected as the preferred option. Scale scores demonstrated construct validity through association with constructs of interest: healthcare distrust, HIV knowledge, perceived proportion of friends/partners on PrEP, perceived community evaluation of PrEP, and perceived effectiveness of PrEP. The scale accounted for 25% of the total variance in reported willingness to be on PrEP, indicating the substantial role PrEP stigma may have on decisions to initiate PrEP. Given increased efforts to roll-out PrEP, having a valid tool to determine the level and types of PrEP stigma in individuals, groups, and communities can help direct implementation plans, identify goals for stigma reduction, and monitor progress over time.

Neonatal mortality risk assessment using SNAPPE- II score in a neonatal intensive care unit.

BACKGROUND: There are many scoring systems to predict neonatal mortality and morbidity in neonatal intensive care units (NICU). One of the scoring systems is SNAPPE-II (Score for Neonatal Acute Physiology with Perinatal extension-II). This study was carried out to assess the validity of SNAPPE-II score (Score for Neonatal Acute Physiology with Perinatal Extension-II) as a predictor of neonatal mortality and duration of stay in a neonatal intensive care unit (NICU). METHODS: This prospective, observational study was carried out over a period of 12 months from June 2015 to May 2016. Two hundred fifty five neonates, who met the inclusion criteria admitted to NICU in tertiary care hospital, BPKIHS Hospital, Nepal were enrolled in the study and SNAPPE-II score was calculated. Receiver Operating Characteristic (ROC) curve was constructed to derive the best SNAPPE-II cut-off score for mortality. RESULTS: A total of 305 neonates were admitted to NICU over a period of one year. Among them, 255 neonates fulfilled the inclusion criteria. Out of 255 neonates, 45 neonates (17.6%) died and 210 were discharged. SNAPPE-II score was significantly higher among neonates who died compared to those who survived [median (IQR) 57 (42-64) vs. 22 (14-32), P < 0.001]. SNAPPE II score had discrimination to predict mortality with area under ROC Curve (AUC): 0.917 (95% CI, 0.854-0.980). The best cut - off score for predicting mortality was 38 with sensitivity 84.4%, specificity 91%, positive predictive value 66.7% and negative predictive value 96.5%. SNAPPE II score could not predict the duration of NICU stay (P = 0.477). CONCLUSION: SNAPPE- II is a useful tool to predict neonatal mortality in NICU. The score of 38 may be associated with higher mortality.

Long-term retention in pre-exposure prophylaxis care among men who have sex with men and transgender women in the United States.

INTRODUCTION: Retention in HIV pre-exposure prophylaxis (PrEP) care in real-world settings, outside of controlled trials or demonstration projects, remains poorly understood. METHODS: We evaluated retention in PrEP care outcomes among men who have sex with men (MSM) and transgender women prescribed PrEP through March 2017 at three clinical sites in the United States (US): Jackson, Mississippi; Providence, Rhode Island; and St. Louis, Missouri. We determined retention rates by attendance of clinical visits every three months, per US Centers for Disease Control and Prevention (CDC) guidelines, as well as by the timing of patients' actual clinical visits. Multivariable analyses examined demographic and behavioural factors associated with retention. RESULTS: From 2013 to 2015, 282 MSM and transgender women were prescribed PrEP; 82% attended a follow-up visit. Based on CDC recommendations, 56% of patients were retained in PrEP care at the first follow-up visit, having attended a visit three months after initiation. However, 76% had a follow-up visit within eight months. Thirty-percent were retained at 12 months by CDC criteria, but 62% were retained when using a 16-month endpoint. Self-reported adherence was strongly correlated with retention. In multivariable analyses, younger age was associated with decreased odds of retention at initial follow-up, and completing college was associated with increased odds of retention at 16 months. Eight participants were newly diagnosed with HIV; six were African American, and seven were under 30 years of age. CONCLUSIONS: Measuring retention in PrEP care using three-month follow-up intervals may underestimate true retention. Nevertheless, retention in PrEP care is suboptimal in real-world settings and should be the focus of future interventions.

Developing and Assessing the Feasibility of a Home-based Preexposure Prophylaxis Monitoring and Support Program.

We piloted PrEP@Home, a preexposure prophylaxis system of remote laboratory and behavioral monitoring designed to replace routine quarterly follow-up visits with home care to reduce the patient and provider burden. The system was highly acceptable and in-demand for future use, and more than one-third of participants reported greater likelihood of persisting in care if available.