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.

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.

2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: A consensus and data-driven methodology involving three international patient cohorts.

OBJECTIVES: To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS. METHODS: We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgement. We then validated the performance of the classification criteria in a separate cohort of patients. RESULTS: The final classification criteria are based on the weighted sum of five items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2, each scoring 3; an abnormal Ocular Staining Score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 min and an unstimulated salivary flow rate of ≤0.1 mL/min, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, that is, 96% (95% CI92% to 98%) and 95% (95% CI 92% to 97%), respectively. CONCLUSION: Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well suited as criteria for enrolment in clinical trials.

Accuracy of Pulse Oximeters Intended for Hypoxemic Pediatric Patients.

OBJECTIVES: Prior studies have shown inaccuracies in pulse oximetry readings at saturations less than 85%; however, no large studies have evaluated new sensors marketed for these low saturations. This study's purpose was to evaluate two sensors with claims of improved accuracy in children with saturations less than 85%. DESIGN: Prospective observational study. SETTING: Single institution; cardiac catheterization laboratory, and operating room. PATIENTS: Fifty patients weighing 3-20 kg with baseline saturations less than 90% undergoing surgical or catheterization procedure. MEASUREMENTS AND MAIN RESULTS: Data collected included demographics, diagnosis, continuous saturations from three different pulse oximeters (Masimo LNCS [Masimo, Irvine, CA], Masimo Blue [Masimo], and Nellcor Max-I [Medtronic, Dublin, Ireland]) and up to four blood samples for co-oximetry as the gold-standard arterial oxygen saturation. Analysis included scatter plots, smoothed regression estimates of mean continuous saturation levels plotted against corresponding arterial oxygen saturation values, and Bland-Altman plots. Bland-Altman analysis indicated increasing levels of bias and variability for decreasing arterial oxygen saturation levels for all three sensors, with a statistically significant increase in mean difference observed for decreasing arterial oxygen saturation level. The Masimo Blue sensor had the lowest mean difference, SD and Bland-Altman limits in patients with saturations less than or equal to 85%. At saturation range of less than or equal to 85% and greater than 75%, 14% of the samples obtained from Masimo Blue, 24% of the readings from the Nellcor, and 31% from the Masimo Standard sensors were greater than or equal to 5% points difference. All three sensors had a further increase in these differences for arterial oxygen saturation values less than 75%. CONCLUSIONS: The Masimo Blue sensor has improved accuracy at saturations 75-85% versus the Nellcor and Masimo Standard sensors. The accuracy of peripheral capillary oxygen saturation of the Masimo Blue sensor was within 5% points of the arterial oxygen saturation the majority of the time. Currently, at saturations less than or equal to 85%, pulse oximetry alone should not be relied on in making clinical decisions.

The SSB-positive/SSA-negative antibody profile is not associated with key phenotypic features of Sjögren's syndrome.

OBJECTIVE: To determine whether the Sjögren's syndrome B (SSB)-positive/Sjögren's syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS. METHODS: Among registrants in the Sjögren's International Collaborative Clinical Alliance (SICCA) with possible or established SS, we compared anti-SSA/anti-SSB reactivity profiles against concurrent phenotypic features. We fitted logistic regression models to explore the association between anti-SSA/anti-SSB reactivity profile and each key SS phenotypic feature, controlling for potential confounders. RESULTS: Among 3297 participants, 2061 (63%) had negative anti-SSA/anti-SSB, 1162 (35%) had anti-SSA with or without anti-SSB, and 74 (2%) anti-SSB alone. Key SS phenotypic features were more prevalent and had measures indicative of greater disease activity in those participants with anti-SSA, either alone or with anti-SSB, than in those with anti-SSB alone or negative SSA/SSB serology. These between-group differences were highly significant and not explained by confounding by age, race/ethnicity or gender. Participants with anti-SSB alone were comparable to those with negative SSA/SSB serology in their association with these key phenotypic features. Among SICCA participants classified with SS on the basis of the American-European Consensus Group or American College of Rheumatology criteria, only 2% required the anti-SSB-alone test result to meet these criteria. CONCLUSIONS: The presence of anti-SSB, without anti-SSA antibodies, had no significant association with SS phenotypic features, relative to seronegative participants. The solitary presence of anti-SSB antibodies does not provide any more support than negative serology for the diagnosis of SS. This serological profile should thus be interpreted cautiously in clinical practice and potentially eliminated from future classification criteria.

Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.

PURPOSE: To assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling. RESULTS: A total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%). CONCLUSION: Treatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

Active squamous metaplasia of the cervical epithelium is associated with subsequent acquisition of human papillomavirus 16 infection among healthy young women.

BACKGROUND: Vulnerability of younger women to human papillomavirus 16 (HPV16) infection has been attributed to the predominance of ectocervical columnar epithelia in this age group. However, squamous metaplastic tissue may be more influential. We examined the extent of ectopy and metaplastic activity as risks for HPV16 acquisition in a prospective cohort. METHODS: Participants were HPV16 negative at the first two visits. Follow-up occurred every 4 months. Ectopy was quantitatively measured on colpophotographs. We calculated metaplastic rate as the difference in ectopy between visits. Cox proportional hazards models were constructed, adjusting for several covariates. RESULTS: Analyses included 198 women (mean baseline age 17 years) for 1734 visits. Mean follow-up was 4.4 years. Incident HPV16 was detected in 36 (18%) women. Metaplastic rate between the two visits before HPV16 detection was significantly associated with incident infection (hazard ratio [HR], 1.17; confidence interval [CI], 1.02-1.33; P = .02). However, ectopy was not significant, whether measured before or concurrent to HPV16 detection (HR range, 0.99-1.00; CI range, .97-1.02; P range, .47-.65). CONCLUSIONS: Dynamic metaplasia rather than the sheer extent of ectopy appears to increase risk for incident HPV16 in healthy young women. This in vivo observation is consistent with the HPV life cycle, during which host cell replication and differentiation supports viral replication.

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.

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.

A comparison of three methods of hemoglobin monitoring in patients undergoing spine surgery.

BACKGROUND: Hemoglobin values (Hb) can facilitate decisions regarding perioperative transfusion management. Currently, Hb can be determined invasively by analyzing blood via laboratory Co-Oximetry (tHb) or by point-of-care HemoCue (HCue). Recently, a new noninvasive, continuous spectrophotometric sensor (Masimo SpHb) was introduced into clinical practice. We compared the accuracy of the SpHb and HCue with tHb. METHODS: Twenty patients, ages 40 to 80 years, were studied. They received general anesthesia and underwent spine surgery in the prone position. All blood samples were obtained from a radial artery catheter. SpHb, tHb, and HCue were determined immediately after induction of anesthesia, but before the start of surgery and approximately every hour thereafter. Primary outcomes were defined on the basis of the following differences between measures: SpHb - tHb or HCue - tHb. All patients had 3 to 5 observations taken on each measure. Differences and absolute differences were analyzed by several techniques to assess accuracy. We also investigated the relationship between observed differences and the following variables: tHb level, duration of surgery, age, weight, and perfusion index. RESULTS: Data consisted of 78 measurements of SpHb, tHb, and HCue made on the 20 patients. Absolute differences between SpHb and tHb were <1.5 g/dL for 61% of observations, between 1.6 to 2.0 g/dL for 16% and >2.0 g/dL for 22% of the observations. Observed differences displayed significant decreases with time and higher perfusion index values. No systematic relationships were observed with age or weight. Except for 1 value, all of the HCue values were <1.0 g/dL of tHb. CONCLUSIONS: Although HCue was consistently accurate, our data confirm that SpHb often correlated well with tHb values. Yet our study indicates that SpHb may not be as accurate as clinically necessary in some patients. Improved refinement of continuous, noninvasive technology, such as SpHb, could address important clinical requirements.

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.

Impact of the lung allocation score on lung transplantation for pulmonary arterial hypertension.

RATIONALE: In 2005, lung allocation for transplantation in the United States changed from a system based on waiting time to a system based on the Lung Allocation Score (LAS). OBJECTIVES: To study the effect of the LAS on lung transplantation for idiopathic pulmonary arterial hypertension (IPAH) compared with other major diagnoses. METHODS: We studied 7,952 adults listed for lung transplantation between 2002 and 2008. Analyses were restricted to patients with IPAH, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). Transplantation, waiting list mortality, and post-transplant mortality were compared between diagnoses for patients listed before and after implementation of the LAS. MEASUREMENTS AND MAIN RESULTS: The likelihood of transplantation from the waiting list increased for all diagnoses after implementation of the LAS. Waiting list mortality decreased for every diagnosis, except for IPAH, which remained unchanged. Implementation of the LAS was not associated with changes in post-transplant mortality for any diagnosis. Under the LAS system, patients with IPAH were less likely to be transplanted than patients with IPF (hazard ratio [HR], 0.53; P < 0.001) or CF (HR, 0.49; P < 0.001) and at greater risk of death on the waiting list than patients with COPD (HR, 3.09; P < 0.001) or CF (HR, 1.83; P = 0.025) after adjustment for demographics and transplant type. Post-transplant mortality for IPAH was not statistically different from that of other diagnoses. CONCLUSIONS: Implementation of the LAS has improved the likelihood of lung transplantation for listed patients with IPAH, but mortality on the waiting list remains high compared with other major diagnoses.

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.

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.

Impaired Fetal Environment and Gestational Age: What Is Driving Mortality in Neonates With Critical Congenital Heart Disease?

Background Infants with critical congenital heart disease (CCHD) are more likely to be small for gestational age (SGA) or born to mothers with maternal placental syndrome. The objective of this study was to investigate the relationship between maternal placental syndrome, SGA, and gestational age (GA) on 1-year mortality in infants with CCHD. Methods and Results In a population-based administrative database of all live-born infants in California (2007-2012) we identified all infants with CCHD without chromosomal anomalies. Our primary predictor was an impaired fetal environment (IFE), defined as presence of maternal placental syndrome or SGA. We calculated hazard ratios to quantify the association between different components of IFE and 1-year mortality and conducted a causal mediation analysis to assess GA at birth as a mediator. We identified 6863 infants with CCHD. IFE was present in 25.1%. Infants with IFE were more likely to die than infants without IFE (16.6% versus 11.1%; hazard ratios 1.55, 95% CI 1.34-1.78). Only SGA (hazard ratios 1.76, 95% CI 1.50-2.05) and placental abruption (hazard ratios 1.70, 95% CI 1.17-2.48) were significantly associated with mortality; preeclampsia and gestational hypertension had no significant association with mortality. The mediation analysis showed that 32.8% (95% CI 24.9-47.0%) of the relationship between IFE and mortality is mediated through GA. Conclusions IFE is a significant contributor to outcomes in the CCHD population. SGA and placental abruption are the main drivers of postnatal mortality while other maternal placental syndrome components had much less of an impact. Only one third of the effect between IFE and mortality is mediated through GA.

Effect of diaphragm and lubricant gel provision on human papillomavirus infection among women provided with condoms: a randomized controlled trial.

OBJECTIVE: To estimate the effect of providing women with a latex diaphragm, lubricant gel, and male condoms (intervention) compared with condoms alone (control) on human papillomavirus (HPV) incidence and clearance. METHODS: Participants were 2,040 human immunodeficiency virus (HIV)-negative Zimbabwean women enrolled in a randomized trial estimating the effect of the intervention on HIV acquisition. Clinicians collected cervical samples for HPV testing at baseline, 12 months, and exit. L1 consensus polymerase chain reaction primers were used to determine HPV presence and type. RESULTS: We found no differences in the following outcomes: HPV prevalence at the time of the first postenrollment HPV test (intention-to-treat analysis, relative risk [RR] 1.02, 95% confidence interval [CI] 0.90-1.16); HPV incidence at 12 months among women HPV-negative at baseline (RR 0.95, 95% CI 0.80-1.14); and HPV clearance at 12 months among women HPV-positive at baseline (RR 0.80, 95% CI 0.61-1.05). Clearance of HPV type 58 was lower in the intervention group at 12 months (RR 0.67, 95% CI 0.48-0.92), but not at exit (RR 0.93, 95% CI 0.75-1.16); clearance of HPV type 18 was lower in the intervention group at exit (RR 0.55, 95% CI 0.33-0.89), but not at 12 months (RR 0.55, 95% CI 0.29-1.05). Women reporting diaphragm/gel use at 100% of prior sex acts had a lower likelihood of having one or more new HPV types detected at 12 months (RR 0.75, 95% CI 0.58-0.96) and exit (RR 0.77, 95% CI 0.59-0.99). CONCLUSION: Among women receiving risk reduction counseling and condoms in an HIV prevention program, diaphragm plus lubricant gel provision did not affect HPV incidence or clearance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00121459 LEVEL OF EVIDENCE: I.

Natural History and Predictors of Progression to Sjögren's Syndrome Among Participants of the Sjögren's International Collaborative Clinical Alliance Registry.

OBJECTIVE: To explore changes in the phenotypic features of Sjögren's syndrome (SS), and in SS status among participants in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry over a 2-3-year interval. METHODS: All participants in the SICCA registry who were found to have any objective measures of salivary hypofunction, dry eye, focal lymphocytic sialadenitis in minor salivary gland biopsy, or anti-SSA/SSB antibodies were recalled over a window of 2 to 3 years after their baseline examinations to repeat all clinical examinations and specimen collections to determine whether there was any change in phenotypic features and in SS status. RESULTS: As of September 15, 2013, a total of 3,514 participants had enrolled in SICCA, and among 3,310 eligible, 771 presented for a followup visit. Among participants found to have SS using the 2012 American College of Rheumatology (ACR) classification criteria, 93% again met the criteria after 2 to 3 years, and this proportion was 89% when using the 2016 ACR/European League Against Rheumatism (EULAR) criteria. Among those who did not meet ACR or ACR/EULAR criteria at baseline, 9% and 8%, respectively, had progressed and met them at followup. Those with hypergammaglobulinemia and hypocomplementemia at study entry were, respectively, 4 and 6 times more likely to progress to SS by ACR criteria than those without these characteristics (95% confidence interval 1.5-10.1 and 1.8-20.4, respectively). CONCLUSION: While there was stability over a 2-3-year period of both individual phenotypic features of SS and of SS status, hypergammaglobulinemia and hypocomplementemia at study entry were predictive of progression to SS.

Health-related quality of life and depression among participants in the Sjögren's International Collaborative Clinical Alliance registry.

OBJECTIVE: To examine health-related quality of life (HRQoL) and depression among participants in an international Sjögren's syndrome (SS) registry, comparing those with and without SS. METHODS: Cross-sectional study of participants in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry. The 2016 American College of Rheumatology/European League Against Rheumatism SS classification criteria were used to determine disease status. HRQoL was assessed using the Short Form 12, version 2 Health Survey to derive scores for physical component summary (PCS) and mental component summary (MCS). Depression was assessed using the 9-Item Patient Health Questionnaire. Multivariate linear and logistic regression analyses were performed to identify predictors of HRQoL and depression while controlling for potential confounders. RESULTS: Among 2401 SICCA participants who had symptoms of dry eyes and dry mouth, 1051 had SS (44%) and 1350 did not (56%). After controlling for confounders, when compared with non-SS participants, those with SS had better PCS (p<0.001, ß=2.43, 95% CI 1.57 to 3.29), MCS (p=0.002, ß=1.37, 95% CI 0.50 to 2.23) and lower adjusted odds of depression (p<0.001, OR 0.67, 95% CI 0.55 to 0.81). Other significant predictors of HRQoL and depression included employment, country of residence and use of medication with anticholinergic effect or for management of SS-related signs and symptoms. CONCLUSION: Our results suggest that among symptomatic patients, having a diagnosis of SS may be associated with better emotional and psychological well-being compared with patients without a diagnosis. Having a definitive diagnosis of SS may encourage patients to obtain a better understanding of their disease and have coping mechanisms in place to better manage their symptoms.

2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren's Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts.

OBJECTIVE: To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS. METHODS: We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgment. We then validated the performance of the classification criteria in a separate cohort of patients. RESULTS: The final classification criteria are based on the weighted sum of 5 items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2 , each scoring 3; an abnormal ocular staining score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 minutes, and an unstimulated salivary flow rate of ≤0.1 ml/minute, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, i.e., 96% (95% confidence interval [95% CI] 92-98%) and 95% (95% CI 92-97%), respectively. CONCLUSION: Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well-suited as criteria for enrollment in clinical trials.