Medication Cost Concerns and Disparities in Patient-Reported Outcomes Among a Multiethnic Cohort of Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Concerns about the affordability of medications are common in systemic lupus erythematosus (SLE), but the relationship between medication cost concerns and health outcomes is poorly understood. We assessed the association of self-reported medication cost concerns and patient-reported outcomes (PROs) in a multiethnic SLE cohort. METHODS: The California Lupus Epidemiology Study is a cohort of individuals with physician-confirmed SLE. Medication cost concerns were defined as having difficulties affording SLE medications, skipping doses, delaying refills, requesting lower-cost alternatives, purchasing medications outside the United States, or applying for patient assistance programs. Linear regression and mixed effects models assessed the cross-sectional and longitudinal association of medication cost concerns and PROs, respectively, adjusting for age, sex, race and ethnicity, income, principal insurance, immunomodulatory medications, and organ damage. RESULTS: Of 334 participants, medication cost concerns were reported by 91 (27%). Medication cost concerns were associated with worse Systemic Lupus Activity Questionnaire (SLAQ; beta coefficient [ß] 5.9, 95% CI 4.3-7.6; P < 0.001), 8-item Patient Health Questionnaire depression scale (PHQ-8; ß 2.7, 95% CI 1.4-4.0; P < 0.001), and Patient-Reported Outcomes Measurement Information System (PROMIS; ß for physical function -4.6, 95% CI -6.7 to -2.4; P < 0.001) scores after adjusting for covariates. Medication cost concerns were not associated with significant changes in PROs over 2-year follow-up. CONCLUSION: More than a quarter of participants reported at least 1 medication cost concern, which was associated with worse PROs. Our results reveal a potentially modifiable risk factor for poor outcomes rooted in the unaffordability of SLE care.

An Electronic Dashboard to Improve Dosing of Hydroxychloroquine Within the Veterans Health Care System: Time Series Analysis.

BACKGROUND: Hydroxychloroquine (HCQ) is commonly used for patients with autoimmune conditions. Long-term use of HCQ can cause retinal toxicity, but this risk can be reduced if high doses are avoided. OBJECTIVE: We developed and piloted an electronic health record-based dashboard to improve the safe prescribing of HCQ within the Veterans Health Administration (VHA). We observed pilot facilities over a 1-year period to determine whether they were able to improve the proportion of patients receiving inappropriate doses of HCQ. METHODS: Patients receiving HCQ were identified from the VHA corporate data warehouse. Using PowerBI (Microsoft Corp), we constructed a dashboard to display patient identifiers and the most recent HCQ dose and weight (flagged if ≥5.2 mg/kg/day). Six VHA pilot facilities were enlisted to test the dashboard and invited to participate in monthly webinars. We performed an interrupted time series analysis using synthetic controls to assess changes in the proportion of patients receiving HCQ ≥5.2 mg/kg/day between October 2020 and November 2021. RESULTS: At the start of the study period, we identified 18,525 total users of HCQ nationwide at 128 facilities in the VHA, including 1365 patients at the 6 pilot facilities. Nationwide, at baseline, 19.8% (3671/18,525) of patients were receiving high doses of HCQ. We observed significant improvements in the proportion of HCQ prescribed at doses ≥5.2 mg/kg/day among pilot facilities after the dashboard was deployed (-0.06; 95% CI -0.08 to -0.04). The difference in the postintervention linear trend for pilot versus synthetic controls was also significant (-0.06; 95% CI -0.08 to -0.05). CONCLUSIONS: The use of an electronic health record-based dashboard reduced the proportion of patients receiving higher than recommended doses of HCQ and significantly improved performance at 6 VHA facilities. National roll-out of the dashboard will enable further improvements in the safe prescribing of HCQ.

Preventing HIV and achieving pregnancy among HIV sero-different couples: Pilot study of a safer conception intervention in Zimbabwe.

Safer conception services are needed to minimize HIV transmission among HIV sero-different couples desiring pregnancy. Few studies have evaluated the choices couples make when offered multiple safer conception methods or real-world method acceptability and effectiveness. We piloted a comprehensive safer conception program (Clintrials.gov identifier: NCT03049176) for HIV sero-different couples planning pregnancy in Zimbabwe to measure feasibility, method uptake, acceptability, pregnancy outcome, and HIV transmission. This study was not designed to compare rates of HIV transmission by safer conception method choice but rather to understand choices couples make when seeking to minimize risk of HIV transmission and maximize likelihood of pregnancy. Couples in this prospective, non-randomized study were given a choice of one or more currently available safer conception methods: antiretroviral therapy (ART) with monthly viral load (VL) monitoring for the HIV-positive partner (ART/VL), pre-exposure prophylaxis (PrEP) for the HIV-negative partner, vaginal insemination (VI) for couples with an HIV-positive woman, and semen washing (SW) for couples with an HIV-positive man. Couples were followed monthly for up to 12 months of pregnancy attempts, quarterly during pregnancy, and 12 weeks post-partum. At each visit, data on method use, urine for pregnancy testing, and blood for HIV antibody testing, or viral load if HIV-positive, were obtained. Infants born to HIV-positive women were tested for HIV at 6 and 12 weeks. Between March 2017 and June 2019, 46 individuals from 23 HIV sero-different partnerships were enrolled and followed. At enrollment, all couples chose ART/VL, and all couples chose at least one additional method; 74% chose PrEP, 36% chose SW, and 25% chose VI. During pre-pregnancy follow-up visits, three couples discontinued SW, and one couple discontinued VI; all four of these couples opted for ART/VL plus PrEP. Satisfaction with safer conception methods was high among those who chose ART/VL and PrEP. Twelve couples achieved pregnancy. There were no cases of HIV transmission to partners, and no infants tested positive for HIV. This safer conception program is feasible and acceptable, allowing sero-different couples to safely achieve pregnancy. Sero-different couples in Zimbabwe seek a combination of HIV prevention methods, particularly ART/VL plus PrEP. Trial Registration: Clintrials.gov, NCT03049176.

Predicting the risk of 7-day readmission in late preterm infants in California: A population-based cohort study.

Background and aims: The American Academy of Pediatrics describes late preterm infants, born at 34 to 36 completed weeks' gestation, as at-risk for rehospitalization and severe morbidity as compared to term infants. While there are prediction models that focus on specific morbidities, there is limited research on risk prediction for early readmission in late preterm infants. The aim of this study is to derive and validate a model to predict 7-day readmission. Methods: This is a population-based retrospective cohort study of liveborn infants in California between January 2007 to December 2011. Birth certificates, maintained by California Vital Statistics, were linked to a hospital discharge, emergency department, and ambulatory surgery records maintained by the California Office of Statewide Health Planning and Development. Random forest and logistic regression were used to identify maternal and infant variables of importance, test for association, and develop and validate a predictive model. The predictive model was evaluated for discrimination and calibration. Results: We restricted the sample to healthy late preterm infants (n = 122,014), of which 4.1% were readmitted to hospital within 7-day after birth discharge. The random forest model with 24 variables had better predictive ability than the 8 variable logistic model with c-statistic of 0.644 (95% confidence interval 0.629, 0.659) in the validation data set and Brier score of 0.0408. The eight predictors of importance length of stay, delivery method, parity, gestational age, birthweight, race/ethnicity, phototherapy at birth hospitalization, and pre-existing or gestational diabetes were used to drive individual risk scores. The risk stratification had the ability to identify an estimated 19% of infants at greatest risk of readmission. Conclusions: Our 7-day readmission predictive model had moderate performance in differentiating at risk late preterm infants. Future studies might benefit from inclusion of more variables and focus on hospital practices that minimize risk.

Examining socioeconomic status disparities in facility-based childbirth in Kenya: role of perceived need, accessibility, and quality of care.

BACKGROUND: Giving birth in health facilities with skilled birth attendants (SBAs) is one of the key efforts promoted to reduce preventable maternal deaths in sub-Saharan Africa. However, research has revealed large socioeconomic status (SES) disparities in facility-based childbirth. We seek to extend the literature on the factors underlying these SES disparities. Drawing on the Disparities in Skilled Birth Attendance (DiSBA) framework, we examined the contribution of three proximal factors-perceived need, accessibility, and quality of care-that influence the use of SBAs. METHODS: We used data from a survey conducted in Migori County, Kenya in 2016, among women aged 15-49 years who gave birth nine weeks before the survey (N = 1020). The primary outcome is facility-based childbirth. The primary predictors are wealth, measured in quintiles calculated from a wealth index based on principal component analysis of household assets, and highest education level attained. Proposed mediating variables include maternal perceptions of need, accessibility (physical and financial), and quality of care (antenatal services received and experience of care). Logistic regression with mediation analysis was used to investigate the mediating effects. RESULTS: Overall, 85% of women in the sample gave birth in a health facility. Women in the highest wealth quintile were more likely to give birth in a facility than women in the lowest quintile, controlling for demographic factors (adjusted odds ratio [aOR]: 2.97, 95% CI: 1.69-5.22). College-educated women were five times more likely than women with no formal education or primary education to give birth in a health facility (aOR: 4.96; 95% CI: 1.43-17.3). Women who gave birth in health facilities had higher perceived accessibility and quality of care than those who gave birth at home. The five mediators were estimated to account for between 15% and 48% of the differences in facility births between women in the lowest and higher wealth quintiles. CONCLUSION: Our results confirm SES disparities in facility-based childbirth, with the proximal factors accounting for some of these differences. These proximal factors - particularly perceived accessibility and quality of care - warrant attention due to their relationship with facility-birth overall, and their impact on inequities in this care.

Association between indoor residual spraying and pregnancy outcomes: a quasi-experimental study from Uganda.

BACKGROUND: Malaria is a risk factor for adverse pregnancy outcomes. Indoor residual spraying with insecticide (IRS) reduces malaria infections, yet the effects of IRS on pregnancy outcomes are not well established. We evaluated the impact of a large-scale IRS campaign on pregnancy outcomes in Eastern Uganda. METHODS: Birth records (n = 59 992) were obtained from routine surveillance data at 25 health facilities from five districts that were part of the IRS campaign and six neighbouring control districts ∼27 months before and ∼24 months after the start of the campaign (January 2013-May 2017). Campaign effects on low birthweight (LBW) and stillbirth incidence were estimated using the matrix completion method (MC-NNM), a machine-learning approach to estimating potential outcomes, and compared with the difference-in-differences (DiD) estimator. Subgroup analyses were conducted by HIV and gravidity. RESULTS: MC-NNM estimates indicated that the campaign was associated with a 33% reduction in LBW incidence: incidence rate ratio (IRR) = 0.67 [95% confidence interval (CI): 0.49-0.93)]. DiD estimates were similar to MC-NNM [IRR = 0.69 (0.47-1.01)], despite a parallel trends violation during the pre-IRS period. The campaign was not associated with substantial reductions in stillbirth incidence [IRRMC-NNM = 0.94 (0.50-1.77)]. HIV status modified the effects of the IRS campaign on LBW [ßIRSxHIV = 0.42 (0.05-0.78)], whereby HIV-negative women appeared to benefit from the campaign [IRR = 0.70 (0.61-0.81)], but not HIV-positive women [IRR = 1.12 (0.59-2.12)]. CONCLUSIONS: Our results support the effectiveness of the campaign in Eastern Uganda based on its benefit to LBW prevention, though HIV-positive women may require additional interventions. The IRS campaign was not associated with a substantively lower stillbirth incidence, warranting further research.

A quasi-experimental study estimating the impact of long-lasting insecticidal nets with and without piperonyl butoxide on pregnancy outcomes.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the main vector control tool for pregnant women, but their efficacy may be compromised, in part, due to pyrethroid resistance. In 2017, the Ugandan Ministry of Health embedded a cluster randomized controlled trial into the national LLIN campaign, where a random subset of health subdistricts (HSDs) received LLINs treated with piperonyl butoxide (PBO), a chemical synergist known to partially restore pyrethroid sensitivity. Using data from a small, non-randomly selected subset of HSDs, this secondary analysis used quasi-experimental methods to quantify the overall impact of the LLIN campaign on pregnancy outcomes. In an exploratory analysis, differences between PBO and conventional (non-PBO) LLINs on pregnancy outcomes were assessed. METHODS: Birth registry data (n = 39,085) were retrospectively collected from 21 health facilities across 12 HSDs, 29 months before and 9 months after the LLIN campaign (from 2015 to 2018). Of the 12 HSDs, six received conventional LLINs, five received PBO LLINs, and one received a mix of conventional and PBO LLINs. Interrupted time-series analyses (ITSAs) were used to estimate changes in monthly incidence of stillbirth and low birthweight (LBW; <2500 g) before-and-after the campaign. Poisson regression with robust standard errors modeled campaign effects, adjusting for health facility-level differences, seasonal variation, and time-varying maternal characteristics. Comparisons between PBO and conventional LLINs were estimated using difference-in-differences estimators. RESULTS: ITSAs estimated the campaign was associated with a 26% [95% CI: 7-41] reduction in stillbirth incidence (incidence rate ratio (IRR) = 0.74 [0.59-0.93]) and a 15% [-7, 33] reduction in LBW incidence (IRR=0.85 [0.67-1.07]) over a 9-month period. The effect on stillbirth incidence was greatest for women delivering 7-9 months after the campaign (IRR=0.60 [0.41-0.87]) for whom the LLINs would have covered most of their pregnancy. The IRRs estimated from difference-in-differences analyses comparing PBO to conventional LLINs was 0.78 [95% CI: 0.52, 1.16] for stillbirth incidence and 1.15 [95% CI: 0.87, 1.52] for LBW incidence. CONCLUSIONS: In this region of Uganda, where pyrethroid resistance is high, this study found that a mass LLIN campaign was associated with reduced stillbirth incidence. Effects of the campaign were greatest for women who would have received LLINs early in pregnancy, suggesting malaria protection early in pregnancy can have important benefits that are not necessarily realized through antenatal malaria services. Results from the exploratory analyses comparing PBO and conventional LLINs on pregnancy outcomes were inconclusive, largely due to the wide confidence intervals that crossed the null. Thus, future studies with larger sample sizes are needed.

Reconsidering the Utility of Race-Specific Lung Function Prediction Equations.

Rationale: African American individuals have worse outcomes in chronic obstructive pulmonary disease (COPD). Objectives: To assess whether race-specific approaches for estimating lung function contribute to racial inequities by failing to recognize pathological decrements and considering them normal. Methods: In a cohort with and at risk for COPD, we assessed whether lung function prediction equations applied in a race-specific versus universal manner better modeled the relationship between FEV1, FVC, and other COPD outcomes, including the COPD Assessment Test, St. George's Respiratory Questionnaire, computed tomography percent emphysema, airway wall thickness, and 6-minute-walk test. We related these outcomes to differences in FEV1 using multiple linear regression and compared predictive performance between fitted models using root mean squared error and Alpaydin's paired F test. Measurements and Main Results: Using race-specific equations, African American individuals were calculated to have better lung function than non-Hispanic White individuals (FEV1, 76.8% vs. 71.8% predicted; P = 0.02). Using universally applied equations, African American individuals were calculated to have worse lung function. Using Hankinson's Non-Hispanic White equation, FEV1 was 64.7% versus 71.8% (P < 0.001). Using the Global Lung Initiative's Other race equation, FEV1 was 70.0% versus 77.9% (P < 0.001). Prediction errors from linear regression were less for universally applied equations compared with race-specific equations when examining FEV1% predicted with the COPD Assessment Test (P < 0.01), St. George's Respiratory Questionnaire (P < 0.01), and airway wall thickness (P < 0.01). Although African American participants had greater adversity (P < 0.001), less adversity was only associated with better FEV1 in non-Hispanic White participants (P for interaction = 0.041). Conclusions: Race-specific equations may underestimate COPD severity in African American individuals.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Associations Between Smoking and Primary Sjögren Syndrome Classification Using the Sjögren's International Collaborative Clinical Alliance Cohort.

OBJECTIVE: The objective of this study was to examine the association of smoking with Primary Sjögren syndrome (pSS) classification and pSS diagnostic test results. We hypothesized that past and current smokers would have lower odds of being classified as having Sjögren syndrome (SS) and lower odds of having abnormal individual SS diagnostic test results compared with nonsmokers. METHODS: Participants with suspected or established pSS were enrolled into the Sjögren's International Collaborative Clinical Alliance (SICCA) registry and had oral, ocular, and rheumatologic examinations performed; blood and saliva samples collected; and labial salivary gland biopsy examinations performed; they also completed questionnaires at baseline. Logistic regression was used to determine whether smoking status was associated with pSS classification and individual pSS diagnostic test results. RESULTS: A total of 3514 participants were enrolled in SICCA. A total of 1541 (52.9%) met classification criteria for pSS. Compared with never smokers, current smokers had reduced odds of being classified as having pSS, reduced odds of having a focus score ≥ 1 and serologic positivity for anti-SSA/anti-SSB antibodies, and lower odds of having abnormal signs or test results of dry eye disease. Compared with never smokers, past smokers did not have a statistically significant reduction in odds of being classified as having pSS and of having abnormal individual pSS diagnostic test results. CONCLUSION: Compared with never smokers, current smokers in the SICCA cohort had lower odds of being classified as having pSS, lower odds of exhibiting abnormal signs and test results for dry eye disease, and lower odds of having a labial salivary gland biopsy supportive of pSS classification. Such negative associations, however, do not suggest that current smoking is of any benefit with respect to pSS.

The Relationship Between Electronic Health Record System and Performance on Quality Measures in the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) Registry: Observational Study.

BACKGROUND: Routine collection of disease activity (DA) and patient-reported outcomes (PROs) in rheumatoid arthritis (RA) are nationally endorsed quality measures and critical components of a treat-to-target approach. However, little is known about the role electronic health record (EHR) systems play in facilitating performance on these measures. OBJECTIVE: Using the American College Rheumatology's (ACR's) RISE registry, we analyzed the relationship between EHR system and performance on DA and functional status (FS) quality measures. METHODS: We analyzed data collected in 2018 from practices enrolled in RISE. We assessed practice-level performance on quality measures that require DA and FS documentation. Multivariable linear regression and zero-inflated negative binomial models were used to examine the independent effect of EHR system on practice-level quality measure performance, adjusting for practice characteristics and patient case-mix. RESULTS: In total, 220 included practices cared for 314,793 patients with RA. NextGen was the most commonly used EHR system (34.1%). We found wide variation in performance on DA and FS quality measures by EHR system (median 30.1, IQR 0-74.8, and median 9.0, IQR 0-74.2), respectively). Even after adjustment, NextGen practices performed significantly better than Allscripts on the DA measure (51.4% vs 5.0%; P<.05) and significantly better than eClinicalWorks and eMDs on the FS measure (49.3% vs 29.0% and 10.9%; P<.05). CONCLUSIONS: Performance on national RA quality measures was associated with the EHR system, even after adjusting for practice and patient characteristics. These findings suggest that future efforts to improve quality of care in RA should focus not only on provider performance reporting but also on developing and implementing rheumatology-specific standards across EHRs.

Does NAFLD mediate the relationship between obesity and type 2 diabetes risk? evidence from the multi-ethnic study of atherosclerosis (MESA).

PURPOSE: To estimate the effect of obesity on type 2 diabetes (T2DM) risk and evaluate to what extent non-alcoholic fatty liver disease (NAFLD) mediates this association. METHODS: Data came from 4,522 adults ages 45-84 participating in the Multi-Ethnic Study of Atherosclerosis cohort. Baseline obesity was defined using established BMI categories. NAFLD was measured by CT scans at baseline and incident T2DM defined as fasting glucose ≥126 mg/dL or use of diabetes medications. RESULTS: Over a median 9.1 years of follow-up between 2000 and 2012, 557 new cases of T2DM occurred. After adjusting for age, sex, race/ethnicity, education, diet and exercise, those with obesity had 4.5 times the risk of T2DM compared to normal weight (hazard ratio [HR] = 4.5, 95% confidence interval [CI]: 3.0, 5.9). The mediation analysis suggested that NAFLD accounted for ~36% (95% CI: 27, 44) of the effect (direct effect HR = 3.2, 95% CI: 2.3, 4.6; indirect effect through NAFLD, HR = 1.4, 95% CI: 1.3, 1.5). CONCLUSIONS: These data suggest that the association between obesity and T2DM risk is partially explained by the presence of NAFLD. Future studies should evaluate if NAFLD could be an effective target to reduce the effect of obesity on T2DM.

Predicting Non-Alcoholic Fatty Liver Disease for Adults Using Practical Clinical Measures: Evidence from the Multi-ethnic Study of Atherosclerosis.

BACKGROUND: Many adults have risk factors for non-alcoholic fatty liver disease (NAFLD). Screening all adults with risk factors for NAFLD using imaging is not feasible. OBJECTIVE: To develop a practical scoring tool for predicting NAFLD using participant demographics, medical history, anthropometrics, and lab values. DESIGN: Cross-sectional. PARTICIPANTS: Data came from 6194 white, African American, Hispanic, and Chinese American participants from the Multi-Ethnic Study of Atherosclerosis cohort, ages 45-85 years. MAIN MEASURES: NAFLD was identified by liver computed tomography (≤ 40 Hounsfield units indicating > 30% hepatic steatosis) and data on 14 predictors was assessed for predicting NAFLD. Random forest variable importance was used to identify the minimum subset of variables required to achieve the highest predictive power. This subset was used to derive (n = 4132) and validate (n = 2063) a logistic regression-based score (NAFLD-MESA Index). A second NAFLD-Clinical Index excluding laboratory predictors was also developed. KEY RESULTS: NAFLD prevalence was 6.2%. The model included eight predictors: age, sex, race/ethnicity, type 2 diabetes, smoking history, body mass index, gamma-glutamyltransferase (GGT), and triglycerides (TG). The NAFLD-Clinical Index model excluded GGT and TG. In the NAFLD-MESA model, the derivation set achieved an AUCNAFLD-MESA = 0.83 (95% CI, 0.81 to 0.86), and the validation set an AUCNAFLD-MESA = 0.80 (0.77 to 0.84). The NAFLD-Clinical Index model was AUCClinical = 0.78 [0.75 to 0.81] in the derivation set and AUCClinical = 0.76 [0.72 to 0.80] in the validation set (pBonferroni-adjusted < 0.01). CONCLUSIONS: The two models are simple but highly predictive tools that can aid clinicians to identify individuals at high NAFLD risk who could benefit from imaging.

Mortality Among Hospitalized Individuals With Systemic Lupus Erythematosus in the US Between 2006 and 2016.

OBJECTIVE: To evaluate time trends in mortality for hospitalized adults with systemic lupus erythematosus (SLE) compared to the general hospitalized population (GHP), and to identify factors associated with increased risk of death among hospitalized SLE patients. METHODS: We used the National (Nationwide) Inpatient Sample to estimate all-cause mortality for adults discharged from community hospitals in the US between 2006 and 2016. Poisson regression models were used to estimate the risk of in-hospital death among all patients, including demographic characteristics, socioeconomic factors, comorbidity score, hospital region, SLE diagnosis, and race/ethnicity as covariates. RESULTS: Among 340,467,049 hospitalizations analyzed, 1,903,279 had a discharge diagnosis of SLE. In adjusted analysis, the risk of inpatient death decreased among hospitalizations for patients with SLE from 2.2% to 1.5% (P < 0.001) between 2006 and 2016. All of the decrease in SLE mortality occurred between 2006 and 2008; after 2008, mortality stabilized at a rate statistically similar to the GHP. Hospitalizations for Black, Hispanic, and Asian/Pacific Islander patients with SLE were more likely to end in death compared to hospitalizations for either White patients with SLE or individuals of the same non-White race/ethnicity without SLE. CONCLUSION: In the largest study of in-hospital SLE mortality published to date, we found significant improvements in mortality for hospitalized patients with SLE in the US from 2006 until 2008, after which mortality stabilized at a level similar to that of the GHP. Our results also demonstrate a persistently high mortality burden among Black and Hispanic patients with SLE in the US and contribute new data revealing high mortality among Asian/Pacific Islander patients with SLE.

Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: a mediation analysis.

BACKGROUND: Trials of intermittent preventive treatment (IPTp) of malaria in pregnant women that compared dihydroartemisinin-piperaquine with the standard of care, sulfadoxine-pyrimethamine, showed dihydroartemisinin-piperaquine was superior at preventing malaria infection, but not at improving birthweight. We aimed to assess whether sulfadoxine-pyrimethamine shows greater non-malarial benefits for birth outcomes than does dihydroartemisinin-piperaquine, and whether dihydroartemisinin-piperaquine shows greater antimalarial benefits for birth outcomes than does sulfadoxine-pyrimethamine. METHODS: We defined treatment as random assignment to sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine before pooling individual participant-level data from 1617 HIV-uninfected pregnant women in Kenya (one trial; n=806) and Uganda (two trials; n=811). We quantified the relative effect of treatment on birthweight (primary outcome) attributed to preventing placental malaria infection (mediator). We estimated antimalarial (indirect) and non-malarial (direct) effects of IPTp on birth outcomes using causal mediation analyses, accounting for confounders. We used two-stage individual participant data meta-analyses to calculate pooled-effect sizes. FINDINGS: Overall, birthweight was higher among neonates of women randomly assigned to sulfadoxine-pyrimethamine compared with women assigned to dihydroartemisinin-piperaquine (mean difference 69 g, 95% CI 26 to 112), despite placental malaria infection being lower in the dihydroartemisinin-piperaquine group (relative risk [RR] 0·64, 95% CI 0·39 to 1·04). Mediation analyses showed sulfadoxine-pyrimethamine conferred a greater non-malarial effect than did dihydroartemisinin-piperaquine (mean difference 87 g, 95% CI 43 to 131), whereas dihydroartemisinin-piperaquine conferred a slightly larger antimalarial effect than did sulfadoxine-pyrimethamine (8 g, -9 to 26), although more frequent dosing increased the antimalarial effect (31 g, 3 to 60). INTERPRETATION: IPTp with sulfadoxine-pyrimethamine appears to have potent non-malarial effects on birthweight. Further research is needed to evaluate monthly dihydroartemisinin-piperaquine with sulfadoxine-pyrimethamine (or another compound with non-malarial effects) to achieve greater protection against malarial and non-malarial causes of low birthweight. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation, and Worldwide Antimalarial Resistance Network.

Per-Contact Infectivity of Hepatitis C Virus Acquisition in Association With Receptive Needle Sharing Exposures in a Prospective Cohort of Young Adult People who Inject Drugs in San Francisco, California.

BACKGROUND: Sharing needles and ancillary injecting equipment is a primary risk exposure for hepatitis C virus (HCV) infection among people who inject drugs (PWID); however, infectivity of these exposures is not well quantified. We aimed to estimate per-event HCV infectivity associated with receptive needle sharing (RNS) among susceptible PWID. METHODS: Participants in a prospective cohort study of young adult PWID who were anti-HCV and HCV RNA negative at baseline and attended at least 2 follow-up study visits between 2003 and 2014 were eligible. Data were selected from the first HCV-negative through the first HCV-positive visit (or last HCV-negative among those uninfected). Anti-HCV and HCV-RNA tests were used to determine infection status. A probabilistic exposure model linking observed HCV infection outcomes to self-reported exposure events was applied to estimate infectivity. RESULTS: Among 344 participants, a maximum likelihood estimate considering RNS yielded a pooled population per RNS event HCV probability of 0.25% (95% confidence interval [CI], 0.10%-0.43%), and 1.12% (95% CI, 0.48%-2.35%) among those who acquired any HCV infection (primary or reinfection). CONCLUSIONS: HCV is highly infectious in association with RNS, a primary injection-related risk exposure. Our infectivity estimate among participants who acquired any HCV infection is 1.7 times higher than that estimated for HIV infection in PWID and 2.24 times higher than that estimated among health care workers exposed through needle sticks. The strengths of this study include the assessment of receptive needle sharing events, the prospective design, and relatively short recall and testing periods. These results can inform transmission models and research to prevent HCV infection.

Ocular Clinical Signs and Diagnostic Tests Most Compatible With Keratoconjunctivitis Sicca: A Latent Class Approach.

PURPOSE: To evaluate the ocular signs and tests for keratoconjunctivitis sicca (KCS) in the absence of a gold standard. METHODS: Cross-sectional study of participants from the Sjögren's International Collaborative Clinical Alliance (SICCA) registry. Participants had oral/ocular/rheumatologic examinations, blood/saliva samples collected, and salivary gland biopsy. Latent class analysis (LCA) identified clusters of patients based on 3 to 4 predictor variables relating to signs or tests of KCS. The resulting model-based "gold standard" classification formed the basis for estimated sensitivity and specificity associated with these predictors. RESULTS: A total of 3514 participants were enrolled into SICCA, with 52.9% classified as SS. LCA revealed a best-fit model with 2 groups. For the gold standard-positive group, an abnormal tear breakup time, ocular staining score (OSS), and Schirmer I had a sensitivity of 99.5%, 91.0%, and 47.4%, respectively. For the gold standard-negative group, an abnormal tear breakup time, OSS, and Schirmer I had a specificity of 32.0%, 84.0%, and 88.5%, respectively. OSS components (fluorescein and lissamine staining), exhibited a sensitivity of 82.6% and 90.5%, respectively, in the gold standard-positive group, whereas these signs in the gold standard-negative group had a specificity of 88.8% and 73.0%, respectively. CONCLUSIONS: OSS and its components (fluorescein and lissamine staining) differentiated 2 groups from each other better than other KCS parameters and had relatively high sensitivity and specificity.

Effect of Acute Stroke Care Regionalization on Intravenous Alteplase Use in Two Urban Counties.

Importance: Intravenous alteplase is an effective treatment for acute ischemic stroke and is significantly underutilized. It is known that stroke centers with accreditation are more likely to provide intravenous alteplase treatment, and therefore, policies that increase the number of certified stroke centers and the number of acute ischemic stroke patients routed to these centers may be beneficial. Objective: To determine whether increasing access to primary stroke centers (regionalization) led to an increase in intravenous alteplase use in acute ischemic stroke patients. Design: An observational, longitudinal study to examine treatment trends with log-link binomial regression modeling to compare pre-post policy implementation changes in the proportions of patients treated with intravenous alteplase in two counties. Setting: Two urban counties, Santa Clara and San Mateo, in the western region of US that regionalized acute stroke care between 2005 and 2010. Participants: Patients with primary or secondary diagnosis of stroke were identified from the statewide patient discharge database by International Classification of Diseases (ICD-9) codes. We linked ambulance and hospital data to create complete patient care records. Main outcomes and measures: Stroke treatment, defined as a documented primary procedure code for intravenous alteplase administration (ICD-9: 99.10). Results: In Santa Clara County, intravenous alteplase was administered to 35 patients (1.7%) in the pre-regionalization period and 240 patients (2.1%) in the post-regionalization period. In San Mateo County, intravenous alteplase was administered to 29 patients (1.3%) in the pre-policy period and 135 patients (3.2%) in the post-policy period. After regionalization of stroke care, intravenous alteplase increased two-fold in San Mateo County [adjusted RR 2.20, p = 0.003, 95% CI (1.31, 3.69)] but did not show any statistically significant change in Santa Clara County [adjusted RR 1.10, p = 0.55, 95% CI (0.80, 1.51)]. In the post-regionalization phase, when compared with Santa Clara County, we found that San Mateo County had greater change in paramedic stroke detection, higher number of transports to primary stroke centers and more frequent use of intravenous alteplase at stroke centers. Conclusions: Our findings suggest that greater post-regionalization improvements in San Mateo County contributed to significantly better county-level thrombolysis use than Santa Clara County.

Insurance impacts survival for children, adolescents, and young adults with bone and soft tissue sarcomas.

BACKGROUND: While racial/ethnic survival disparities have been described in pediatric oncology, the impact of income has not been extensively explored. We analyzed how public insurance influences 5-year overall survival (OS) in young patients with sarcomas. METHODS: The University of California San Francisco Cancer Registry was used to identify patients aged 0-39 diagnosed with bone or soft tissue sarcomas between 2000 and 2015. Low-income patients were defined as those with no insurance or Medicaid, a means-tested form of public insurance. Survival curves were computed using the Kaplan-Meier method and compared using log-rank tests and Cox models. Causal mediation was used to assess whether the association between public insurance and mortality is mediated by metastatic disease. RESULTS: Of 1106 patients, 39% patients were classified as low-income. Low-income patients were more likely to be racial/ethnic minorities and to present with metastatic disease (OR 1.96, 95% CI 1.35-2.86). Low-income patients had significantly worse OS (61% vs 71%). Age at diagnosis and extent of disease at diagnosis were also independent predictors of OS. When stratified by extent of disease, low-income patients consistently had significantly worse OS (localized: 78% vs 84%, regional: 64% vs 73%, metastatic: 23% vs 30%, respectively). Mediation analysis indicated that metastatic disease at diagnosis mediated 15% of the effect of public insurance on OS. CONCLUSIONS: Low-income patients with bone and soft tissue sarcomas had decreased OS regardless of disease stage at presentation. The mechanism by which insurance status impacts survival requires additional investigation, but may be through reduced access to care.

HCV incidence is associated with injecting partner age and HCV serostatus mixing in young adults who inject drugs in San Francisco.

BACKGROUND: HCV incidence is increasing in the US, notably among younger people who inject drugs (PWID). In a cohort of young adult (age<30 years) PWID in San Francisco we examined whether 'injecting partner mixing' factors, i.e. age of partner and knowledge of their HCV serostatus, were associated with HCV transmission. METHODS: In 448 susceptible PWID studied prospectively. All participants were asked to report characteristics and behaviors they engaged in with up to 3 injecting partners defined as "people whom you injected the most with" in the past month". These partnerships did not specify that drugs or injecting equipment was shared. HCV incidence was estimated by age of up to 3 injecting partners, categorized as: (i) all <30; (ii) mixed-age (<&≥30); and (iii) all ≥30 years and perceived knowledge of the HCV status of participants' injecting partners' HCV status. Interaction was evaluated between partnership age categories and perceived HCV status of partners. RESULTS: Between 2006-2018, overall HCV incidence (/100 person years observation [pyo]) was 19.4 (95% CI: 16.4, 22.9). Incidence was highest in those with mixed-age partnerships: 28.5 (95% CI: 21.8, 37.1) and those whose partners were all <30 (23.9; 95% CI: 18.8, 30.4), and lowest if partners were ≥30 (7.5; 95% CI: 4.8, 11.8). In a multivariable analyses adjusting for age, sex (of index), injection frequency, and injection partnership 'monogamy', we found evidence for an interaction: the highest HCV incidence was seen in PWID whose partners were all <30 and who knew at least one of their partners was HCV-positive (58.9, 95% CI: 43.3, 80.0; p<0.01). CONCLUSIONS: Younger injectors are more likely to acquire HCV from their similarly-aged peers, than older injecting partners. Protective seroadaptive behavior may contribute to reduce incidence. These findings can inform new HCV prevention approaches for young PWID needed to curb the HCV epidemic.