Brain Health Registry Study Partner Portal: Novel infrastructure for digital, dyadic data collection.

BACKGROUND: In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression. METHODS: Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated. RESULTS: A total of 10,494 BHR participants (mean age = 66.9 ± 12.16 standard deviations, 67.4% female) have enrolled study partners (mean age = 64.3 ± 14.3 standard deviations, 49.3% female), including 8987 dyads with a participant 55 years of age or older. Older and more educated study partners were more likely to complete tasks and return for follow-up. Twenty-five percent to 27% of older adult participants had self and study partner-report ECog scores indicating a possible cognitive impairment. DISCUSSION: The BHR Study Partner Portal is a unique digital tool for capturing dyadic data, with high impact applications in the clinical neuroscience and AD fields. Highlights The Brain Health Registry (BHR) Study Partner Portal is a novel, digital platform of >10,000 dyads. Collection of dyadic online subjective cognitive and functional data is feasible. The portal has good usability as evidenced by positive study partner feedback. The portal is a potential scalable strategy for cognitive impairment screening in older adults.

Digital culturally tailored marketing for enrolling Latino participants in a web-based registry: Baseline metrics from the Brain Health Registry.

INTRODUCTION: This culturally tailored enrollment effort aims to determine the feasibility of enrolling 5000 older Latino adults from California into the Brain Health Registries (BHR) over 2.25 years. METHODS: This paper describes (1) the development and deployment of culturally tailored BHR websites and digital ads, in collaboration with a Latino community science partnership board and a marketing company; (2) an interim feasibility analysis of the enrollment efforts and numbers, and participant characteristics (primary aim); as well as (3) an exploration of module completion and a preliminary efficacy evaluation of the culturally tailored digital efforts compared to BHR's standard non-culturally tailored efforts (secondary aim). RESULTS: In 12.5 months, 3603 older Latino adults were enrolled (71% of the total California Latino BHR initiative enrollment goal). Completion of all BHR modules was low (6%). DISCUSSION: Targeted ad placement, culturally tailored enrollment messaging, and culturally tailored BHR websites increased enrollment of Latino participants in BHR, but did not translate to increased module completion. HIGHLIGHTS: Culturally tailored social marketing and website improvements were implemented. The efforts enrolled 5662 Latino individuals in 12.5 months. The number of Latino Brain Health Registry (BHR) participants increased by 122.7%. We failed to adequately enroll female Latinos and Latinos with lower education. Future work will evaluate effects of a newly released Spanish-language BHR website.

The Impact of Median Model for End-Stage Liver Disease at Transplant Minus 3 National Policy on Waitlist Outcomes in Patients With and Without Hepatocellular Carcinoma.

As a result of ongoing regional disparities, the United Network for Organ Sharing (UNOS) implemented policy in May 2019 limiting exception points for waitlisted patients with hepatocellular carcinoma (HCC) to median Model for End-Stage Liver Disease at transplant in the area surrounding a transplant center minus 3 points (MMAT-3). The impact of this policy change remains unknown. We included adult patients with HCC (n = 4567) and without HCC (n = 19,773) in the UNOS database added to the waiting list before this policy change (May 7, 2017-May 18, 2019) and after (May 19, 2019-March 7, 2020). Cumulative incidence analysis estimated the probability of dropout within 1 year of listing decreased from 12.9% before the policy to 11.1% after the policy in candidates without HCC and from 14% to 10.7% in candidates with HCC. Incidence rates of liver transplantation (LT) and waitlist dropout varied significantly before the policy in patients with HCC and without HCC but nearly equalized in the postpolicy era. These effects were observed in both shorter and longer wait regions. With policy change being modeled as a time-dependent covariate, competing risk regression analyses estimated a decreased risk of dropout after policy change in the non-HCC group (cause-specific hazard ratio, 0.91; P = 0.02) after adjusting for demographic variables. These results suggest that the MMAT-3 policy has successfully reduced disparities in access to LT including across UNOS wait regions, although certain patients with HCC are now disadvantaged.

Synchronous Versus Metachronous Colorectal Liver Metastasis Yields Similar Survival in Modern Era.

BACKGROUND: Synchronous colorectal cancer liver metastasis (CRLM) has been viewed as being more aggressive and having shorter survival than metachronous disease. Advances in CRLM management led us to examine differences in treatment characteristics of synchronous versus metachronous CRLM patients along with survival and recurrence. MATERIALS AND METHODS: A retrospective review of hepatic resection for CRLM at a tertiary academic medical center was performed for two periods: a historic cohort from 1992 to 2010 (n = 121), and a modern cohort (n = 179) from 2012 to 2018. Clinical variables were compared between the patient groups, and survival outcomes were characterized. RESULTS: Five-year disease-specific survival for the modern synchronous group compared to the historic synchronous group was 71.7% versus 44.3% (P = 0.02). Modern metachronous versus modern synchronous 5-y disease-specific survival rates were 49.8% versus 71.7% (P = 0.31). Compared to the historic cohort, the modern one had significantly different timing of hepatic resection (P < 0.01) with increased use of liver-first (30.1% versus 7.5%) and simultaneous liver-colon resections (24.1% versus 10.4%), along with greater use of neoadjuvant chemotherapy (96.4% versus 65.6%; P < 0.01). Significantly more patients in the modern synchronous cohort had disease-free or alive-with-disease status at last follow-up, compared to the historic group (P < 0.01), and experienced less disease recurrence (62.7% versus 77.6%; P < 0.05). CONCLUSIONS: Modern synchronous CRLM patients who underwent hepatic resection experienced significantly improved survival compared to a historic cohort. We postulate that increased use of neoadjuvant chemotherapy and liver-first/simultaneous liver-colon resections in the modern synchronous cohort contributed to improved survival.

The association between frailty and detrusor overactivity in older adults.

OBJECTIVE: To explore the relationship between frailty, age, and detrusor overactivity (DO) in older adults presenting to an academic urology practice. MATERIALS AND METHODS: This study uses the University of California, San Francisco Geriatric Urology Database to examine all adults ages ≥65 years who underwent urodynamic testing from December 2015 to April 2019. All subjects had a timed up and go test (TUGT) as a measure of frailty and were categorized as fast (≤10 seconds), intermediate (11-14 seconds), or slow (≥15 seconds), corresponding to not frail, pre-frail, and frail, respectively. Urodynamic studies were reviewed for the presence of DO. Univariate and multivariate logistic regression were used to examine the relationship between frailty, age, and the presence of DO. RESULTS: In total, 549 older adults underwent urodynamics during the study period, and 48.5% had a study that demonstrated DO. Individuals with DO tended to be older (18.4% vs 11.0% were ≥80 years; P = .01) and more frail (19.5% vs 13.4% with TUGT ≥5 seconds; P < .01). Multivariate regression demonstrated that DO was associated with both pre-frail and frail TUGT times (adjusted odds ratio [aOR], 2.1; 95% confidence interval [CI], 1.3-3.4; P < .01 for TUGT 11-14 seconds, and aOR, 2.1; 95% CI, 1.1-4.0; P = .02 for TUGT ≥15 seconds). Age was not found to be significantly associated with DO (P's > .05). CONCLUSIONS: Frailty, not age, is associated with DO among older adults undergoing urodynamics. Further research on the role of frailty in the evaluation and management of older adults with DO is warranted to best serve the needs of this population.

Validation of online functional measures in cognitively impaired older adults.

INTRODUCTION: Assessment of functional status is associated with risk of cognitive decline and diagnosis of dementia, and can be assessed by participants and study partners (SPs). METHODS: In 770 older adults enrolled in the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study and the online Brain Health Registry (BHR), we estimated associations between online assessments and clinical variables related to Alzheimer's disease (AD) risk. RESULTS: Worse online learning scores and SP-reported functional decline were associated with higher probability of AD dementia diagnosis and poor in-clinic cognitive assessment, and with higher odds of amyloid beta (Aß) positivity when combined with participants' report of less decline. SP report of functional decline conferred predictive value independent of online cognitive assessments. Participants underreported decline compared to SPs. DISCUSSION: The results support the validity of online assessments and their greater utilization in healthcare and research settings. Online SP-reported functional decline is an indicator of dementia and AD risk.

Antiretroviral Concentrations in Hair Strongly Predict Virologic Response in a Large Human Immunodeficiency Virus Treatment-naive Clinical Trial.

Concentrations of antiretrovirals in hair are associated with virologic outcomes in cohorts of human immunodeficiency virus (HIV)-positive individuals but have never been examined in a clinical trial. We show for the first time the predictive utility of hair antiretroviral concentrations in a large HIV treatment-naive trial (AIDS Clinical Trials Group protocol A5257).

Association of Postoperative Antibiotics With Surgical Site Infection in Mohs Micrographic Surgery.

BACKGROUND: Surgical site infection (SSI) is the most frequent complication of Mohs micrographic surgery. Previous studies have identified risk factors for SSI, but it is not known whether antibiotic prophylaxis mitigates this risk. OBJECTIVE: To measure the association between antibiotic prophylaxis and SSI in a convenience sample of Mohs cases and to report on the utility of propensity scoring to control for confounding by indication in registry data. METHODS: Data were drawn from a pilot quality improvement registry of 816 Mohs cases. The relationship between antibiotic prophylaxis and SSI was assessed with logistic regression modeling using propensity score methods to adjust for confounding. RESULTS: One hundred fifty-one cases were prescribed antibiotic prophylaxis (18.5%). Of 467 cases with follow-up, 16 (3.4%) developed SSI. Infection rates were higher in subjects prescribed prophylaxis, but propensity adjustment reduced this effect. Adjusted odds of infection were 1.47-fold higher in subjects prescribed antibiotics and not statistically significant (95% confidence interval 0.29-7.39; p = .64). CONCLUSION: Although there was no significant difference in SSI among patients prescribed prophylactic antibiotics, statistical precision was limited by the low incidence of infection. Larger population-based prospective registry studies including propensity adjustment are needed to confirm the benefit of prophylactic antibiotics in high-risk surgical cases.

Frailty and the Role of Obliterative versus Reconstructive Surgery for Pelvic Organ Prolapse: A National Study.

PURPOSE: We sought to determine whether frailty affects the type of pelvic organ prolapse surgery performed and the odds of postoperative complications. MATERIALS AND METHODS: This is a retrospective cohort study of women who underwent obliterative and reconstructive surgery for pelvic organ prolapse in ACS (American College of Surgeons) NSQIP® (National Surgical Quality Improvement Program) from 2005 to 2013. We quantified frailty using NSQIP-FI (Frailty Index) and applied logistic regression models predicting the type of procedure (colpocleisis) and the odds of postoperative complications. RESULTS: We identified a total of 12,731 women treated with pelvic organ prolapse repair, of which 5.3% were colpocleisis procedures, from 2005 to 2013. Among women undergoing colpocleisis, the average age was 79.2 years and 28.5% had a NSQIP-FI of 0.18 or higher, indicating frailty. Women undergoing colpocleisis procedures had higher odds of being frail (NSQIP-FI 0.18 vs 0 OR 1.9, 95% CI 1.4-2.6) and were older (age 85+ vs less than 65 years OR 486.4, 95% CI 274.6-861.7). For all types of pelvic organ prolapse procedures, frailty increased the odds of complications (NSQIP-FI 0.18 vs 0 OR 2.8, 95% CI 1.8-3.0), after adjusting for age and type of pelvic organ prolapse procedure. CONCLUSIONS: For pelvic organ prolapse surgery, age rather than frailty is more strongly associated with the type of procedure performed. However, frailty is more strongly associated with postoperative complications than age. Furthermore, incorporating frailty into preoperative decision making is important to improve expectations and outcomes among older women considering pelvic organ prolapse surgery.

Tumor recurrence of keratinocyte carcinomas judged appropriate for Mohs micrographic surgery using Appropriate Use Criteria.

BACKGROUND: The use of Mohs micrographic surgery (MMS) has increased greatly to treat basal cell and cutaneous squamous cell carcinomas (keratinocyte carcinoma [KC]), and consensus-based Appropriate Use Criteria (AUC) were developed to identify tumors for which MMS is appropriate. OBJECTIVE: We sought to compare recurrence rates after different treatments in tumors judged appropriate for MMS. METHODS: We used data from an observational prospective cohort study and retrospectively categorized consecutive tumors as appropriate for MMS according to the AUC. Among appropriate tumors, we used survival analyses to compare 5-year recurrence rates after treatments. RESULTS: Among tumors appropriate for MMS (N = 1483), adjusted 5-year recurrence rates were 2.9% (range, 1.4-4.3%) after MMS, 5.5% (range, 3.1-7.9%) after excision, 4.0% (range, 0.6-7.2%) after destruction, and 5.9% (range, 1.5-10.2%) after other treatments. In tumors treated only with MMS or excision (the most similar subgroups), the adjusted hazard ratio of 5-year recurrence after MMS was 0.6 (95% confidence interval, 0.3-1.0; P = .06). LIMITATIONS: This study is limited by its uncertain generalizability, lack of randomization, and unmeasured characteristics. CONCLUSION: The AUC identified tumors for which recurrence would be less common after MMS than after excision, but the absolute difference in recurrence rates was small.

MR T1ρ and T2 of meniscus after acute anterior cruciate ligament injuries.

OBJECTIVE: To evaluate differences in meniscal T1ρ and T2 quantification in patients with acute anterior cruciate ligament (ACL) injuries and to determine correlations of these differences with MR morphological grading and patient-reported outcomes. DESIGN: Bilateral knees of 52 patients with acute ACL injury and 20 healthy controls were scanned using 3 T magnetic resonance imaging (MRI) T1ρ and T2 mapping in this prospective study. Quantitative analysis of the meniscus was performed in anterior and posterior horns of the lateral and medial menisci. Morphological meniscal damage was assessed using modified whole-organ MRI scores (WORMS). Measurements were compared between injured, uninjured contralateral, and control knees using a mixed-effects regression model. Correlations between meniscal T1ρ/T2, WORMS and Knee Injury and Osteoarthritis Outcome Scores (KOOS) were examined using partial correlation analysis. RESULTS: Mean meniscal T1ρ and T2 values were significantly higher in ACL-injured knees compared to control and contralateral knees. Menisci of ACL-injured knees without tears, including those limited to modified meniscal WORMS grade 0, also had significantly higher T1ρ and T2 values compared to menisci of uninjured knees. Within ACL-injured knees, T1ρ and T2 values showed significant positive associations with meniscal WORMS and significant negative associations with KOOS. CONCLUSION: Acute ACL injuries are associated with significantly increased meniscal T1ρ and T2 values in both patients with and without meniscal lesions or tears, suggesting quantitative MRI provides more sensitive measures of meniscal differences compared to traditional morphological MRI sequences. Correlation between meniscal T1ρ/T2 and KOOS suggest that quantitative MRI is reflective of the extent of patients' clinical symptoms.

Impact of frailty on complications in patients undergoing common urological procedures: a study from the American College of Surgeons National Surgical Quality Improvement database.

OBJECTIVES: To evaluate the association of frailty, a measure of diminished physiological reserve, with both major and minor surgical complications among patients undergoing urological surgery. MATERIALS AND METHODS: Using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) from 2007 to 2013, we identified all urological cases that appeared > 1000 times in the dataset among patients aged ≥40 years. Frailty was measured using the NSQIP frailty index (FI), a validated measure that includes 11 impairments, such as decreased functional status and impaired sensorium. We created multivariable logistic regression models using the NSQIP FI to assess major and minor complications after surgery. RESULTS: We identified 95 108 urological cases representing 21 urological procedures. The average frequency of complications per individual was 11.7%, with the most common complications being hospital readmission (6.2%), blood transfusion (4.6%) and urinary tract infection (3.1%). Major and minor complications increased with increasing NSQIP FI. Frailty remained strongly associated with complications after adjustment for year, age, race, smoking status and method of anaesthesia (adjusted odds ratio 1.74 [95% confidence interval 1.64, 1.85] for an NSQIP FI ≥0.18). Increasing NSQIP FI was associated with increasing frequency of complications within age groups (by decade) up to age 81 years and across most procedures. CONCLUSION: Frailty strongly correlates with risk of postoperative complications among patients undergoing urological surgery. This finding is true within most age groups and across most urological procedures.

Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression.

OBJECTIVE: To identify genes affected by advancing gestation and racial/ethnic origin in human ductus arteriosus (DA). STUDY DESIGN: We collected 3 sets of DA tissue (n = 93, n = 89, n = 91; total = 273 fetuses) from second trimester pregnancies. We examined four genes, with DNA polymorphisms that distribute along racial lines, to identify "Caucasian" and "non-Caucasian" DA. We used real time polymerase chain reaction to measure RNA expression of 48 candidate genes involved in functional closure of the DA, and used multivariable regression analyses to examine the relationships between advancing gestation, "non-Caucasian" race, and gene expression. RESULTS: Mature gestation and non-Caucasian race are significant predictors for identifying infants who will close their patent DA when treated with indomethacin. Advancing gestation consistently altered gene expression in pathways involved with oxygen-induced constriction (eg, calcium-channels, potassium-channels, and endothelin signaling), contractile protein maturation, tissue remodeling, and prostaglandin and nitric oxide signaling in all 3 tissue sets. None of the pathways involved with oxygen-induced constriction appeared to be altered in "non-Caucasian" DA. Two genes, SLCO2A1 and NOS3, (involved with prostaglandin reuptake/metabolism and nitric oxide production, respectively) were consistently decreased in "non-Caucasian" DA. CONCLUSIONS: Prostaglandins and nitric oxide are the most important vasodilators opposing DA closure. Indomethacin inhibits prostaglandin production, but not nitric oxide production. Because decreased SLCO2A1 and NOS3 expression can lead to increased prostaglandin and decreased nitric oxide concentrations, we speculate that prostaglandin-mediated vasodilation may play a more dominant role in maintaining the "non-Caucasian" patent DA, making it more likely to close when inhibited by indomethacin.

Assessment of HIV antiretroviral therapy adherence by measuring drug concentrations in hair among children in rural Uganda.

Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child's age, sex, and CD4 count percentage (CD4%). One hundred and twenty-one children aged 2-10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a nonsignificant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have nonsignificant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies.

Incidence of Fit Test Failure During N95 Respirator Reuse and Extended Use.

Importance: The COVID-19 pandemic resulted in a widespread acute shortage of N95 respirators, prompting the Centers for Disease Control and Prevention to develop guidelines for extended use and limited reuse of N95s for health care workers (HCWs). While HCWs followed these guidelines to conserve N95s, evidence from clinical settings regarding the safety of reuse and extended use is limited. Objective: To measure the incidence of fit test failure during N95 reuse and compare the incidence between N95 types. Design, Setting, and Participants: This prospective cohort study, conducted from April 2, 2021, to July 15, 2022, at 6 US emergency departments (EDs), included HCWs who practiced N95 reuse for more than half of their clinical shift. Those who were unwilling to wear an N95 for most of their shift, repeatedly failed baseline fit testing, were pregnant, or had facial hair or jewelry that interfered with the N95 face seal were excluded. Exposures: Wearing the same N95 for more than half of each clinical shift and for up to 5 consecutive shifts. Participants chose an N95 model available at their institution; models were categorized into 3 types: dome (3M 1860R, 1860S, and 8210), trifold (3M 1870+ and 9205+), and duckbill (Halyard 46727, 46767, and 46827). Participants underwent 2 rounds of testing using a different mask of the same type for each round. Main Outcomes and Measures: The primary outcome was Occupational Safety and Health Administration-approved qualitative fit test failure. Trained coordinators conducted fit tests after clinical shifts and recorded pass or fail based on participants tasting a bitter solution. Results: A total of 412 HCWs and 824 N95s were fit tested at baseline; 21 N95s (2.5%) were withdrawn. Participants' median age was 34.5 years (IQR, 29.5-41.8 years); 252 (61.2%) were female, and 205 (49.8%) were physicians. The overall cumulative incidence of fit failure after 1 shift was 38.7% (95% CI, 35.4%-42.1%), which differed by N95 type: dome, 25.8% (95% CI, 21.2%-30.6%); duckbill, 28.3% (95% CI, 22.2%-34.7%); and trifold, 61.3% (95% CI, 55.3%-67.3%). The risk of fit failure was significantly higher for trifold than dome N95s (adjusted hazard ratio, 1.75; 95% CI, 1.46-2.10). Conclusions and Relevance: In this cohort study of ED HCWs practicing N95 reuse, fit failure occurred in 38.7% of masks after 1 shift. Trifold N95s had higher incidence of fit failure compared with dome N95s. These results may inform pandemic preparedness, specifically policies related to N95 selection and reuse practices.

Participant completion of longitudinal assessments in an online cognitive aging registry: The role of medical conditions.

INTRODUCTION: This study aimed to understand whether older adults' longitudinal completion of assessments in an online Alzheimer's disease and related dementias (ADRD)-related registry is influenced by self-reported medical conditions. METHODS: Brain Health Registry (BHR) is an online cognitive aging and ADRD-related research registry that includes longitudinal health and cognitive assessments. Using logistic regressions, we examined associations between longitudinal registry completion outcomes and self-reported (1) number of medical conditions and (2) eight defined medical condition groups (cardiovascular, metabolic, immune system, ADRD, current psychiatric, substance use/abuse, acquired, other specified conditions) in adults aged 55+ (N = 23,888). Longitudinal registry completion outcomes were assessed by the completion of the BHR initial questionnaire (first questionnaire participants see at each visit) at least twice and completion of a cognitive assessment (Cogstate Brief Battery) at least twice. Models included ethnocultural identity, education, age, and subjective memory concern as covariates. RESULTS: We found that the likelihood of longitudinally completing the initial questionnaire was negatively associated with reporting a diagnosis of ADRD and current psychiatric conditions but was positively associated with reporting substance use/abuse and acquired medical conditions. The likelihood of longitudinally completing the cognitive assessment task was negatively associated with number of reported medical conditions, as well as with reporting cardiovascular conditions, ADRD, and current psychiatric conditions. Previously identified associations between ethnocultural identity and longitudinal assessment completion in BHR remained after accounting for the presence of medical conditions. DISCUSSION: This post hoc analysis provides novel, initial evidence that older adults' completion of longitudinal assessments in an online registry is associated with the number and types of participant-reported medical conditions. Our findings can inform future efforts to make online studies with longitudinal health and cognitive assessments more usable for older adults with medical conditions. The results need to be interpreted with caution due to selection biases, and the under-inclusion of minoritized communities.

Defining a screening tool for post-traumatic stress disorder in East Africa: a penalized regression approach.

Background: Scalable PTSD screening strategies must be brief, accurate and capable of administration by a non-specialized workforce. Methods: We used PTSD as determined by the structured clinical interview as our gold standard and considered predictors sets of (a) Posttraumatic Stress Checklist-5 (PCL-5), (b) Primary Care PTSD Screen for the DSM-5 (PC-PTSD) and, (c) PCL-5 and PC-PTSD questions to identify the optimal items for PTSD screening for public sector settings in Kenya. A logistic regression model using LASSO was fit by minimizing the average squared error in the validation data. Area under the receiver operating characteristic curve (AUROC) measured discrimination performance. Results: Penalized regression analysis suggested a screening tool that sums the Likert scale values of two PCL-5 questions-intrusive thoughts of the stressful experience (#1) and insomnia (#21). This had an AUROC of 0.85 (using hold-out test data) for predicting PTSD as evaluated by the MINI, which outperformed the PC-PTSD. The AUROC was similar in subgroups defined by age, sex, and number of categories of trauma experienced (all AUROCs>0.83) except those with no trauma history- AUROC was 0.78. Conclusion: In some East African settings, a 2-item PTSD screening tool may outperform longer screeners and is easily scaled by a non-specialist workforce.

The association of self-perception of body fat changes and quality of life in the Women's Interagency HIV Study.

Body fat changes are of concern to HIV-seropositive adults on highly active antiretroviral therapy (HAART). Studies examining the association of body fat changes and quality of life (QOL) in the setting of HIV infection have been conducted predominately in men. We examined the relationship of self-perceived body fat change with QOL among 1671 HAART-using HIV-seropositive women (mean age 40±8 years; 54% African-American, 24% reporting <95% HAART adherence) from the Women's Interagency HIV Study. Self-perception of any fat loss was associated with lower overall QOL. Report of any peripheral fat loss was strongly associated with nearly all QOL domains (i.e., physical functioning, role functioning, energy/fatigue, social functioning, pain, emotional well-being, health perception, and perceived health index) except cognitive functioning, whereas report of any central fat loss was significantly associated with lower social and cognitive functioning. Report of any central fat gain was associated with lower overall QOL, but only physical functioning, energy/fatigue, and cognitive functioning were significantly affected. A significant association of report of any peripheral fat gain with overall QOL was not observed, however, peripheral fat gain was significantly associated with lower physical functioning and pain. We found that any report of fat loss, especially in peripheral body sites was associated with lower QOL, as was any report of central fat gain. Ultimately health providers and patients need to be informed of these associations so as to better support HIV-seropositive women who live with these effects.

A single-nucleotide polymorphism in CYP2B6 leads to >3-fold increases in efavirenz concentrations in plasma and hair among HIV-infected women.

BACKGROUND: Efavirenz exhibits marked interindividual variability in plasma levels and toxicities. Prior pharmacogenetic studies usually measure exposure via single plasma levels, examine limited numbers of polymorphisms, and rarely model multiple contributors. We analyzed numerous genetic and nongenetic factors impacting short-term and long-term exposure in a large heterogeneous population of human immunodeficiency virus (HIV)-infected women. METHODS: We performed 24-hour intensive pharmacokinetic studies in 111 women receiving efavirenz under actual-use conditions and calculated the area-under-the-concentration-time curve (AUC) to assess short-term exposure; the efavirenz concentration in hair was measured to estimate long-term exposure. A total of 182 single-nucleotide polymorphisms (SNPs) and 45 haplotypes in 9 genes were analyzed in relationship to exposure by use of multivariate models that included a number of nongenetic factors. RESULTS: Efavirenz AUCs increased 1.26-fold per doubling of the alanine aminotransferase level and 1.23-fold with orange and/or orange juice consumption. Individuals with the CYP2B6 516TT genotype displayed 3.5-fold increases in AUCs and 3.2-fold increases in hair concentrations, compared with individuals with the TG/GG genotype. Another SNP in CYP2B6 (983TT) and a p-glycoprotein haplotype affected AUCs without substantially altering long-term exposure. CONCLUSIONS: This comprehensive pharmacogenomics study showed that individuals with the CYP2B6 516TT genotype displayed >3-fold increases in both short-term and long-term efavirenz exposure, signifying durable effects. Pharmacogenetic testing combined with monitoring of hair levels may improve efavirenz outcomes and reduce toxicities.