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Purpose: Epidemiological TB data indicate differences in infection prevalence, progression rates, and clinical disease incidence between sexes. In contrast, evidence on sex-specific differential (post) TB case fatality in Europe has not been synthesized systematically. Methods: We searched electronic databases and grey literature up to December 2020 for studies reporting sex-stratified TB death data for Europe. The JBI critical appraisal tools served for bias risk assessment and subgroup analyses for studying heterogeneity. Random-effects models meta-analyses enabled estimating pooled relative risks of sex-associated TB fatality. Considering associations of comorbidities and risk factors on fatality differences, we applied relative risk meta-regression. Results: Based on 17,400 records screened, 117 studies entered quantitative analyses. Seventy-five studies providing absolute participant data with moderate quality and limited sex stratification reported 33 to 235,000 TB cases and 7 to 27,108 deaths. The pooled male-to-female TB fatality risk ratio was 1.4 [1.3–1.5]. Heterogeneity was high between studies and subgroups. Study time, concurrent comorbidities (e.g., HIV, diabetes, cancers), and mean participant ages showed no effect modification. We identified higher male TB fatality in studies with higher homelessness (coefficient 3.18, 95% CI [-0.59 to 6.94], p-value 0.10) and lower migrants proportion (coefficient − 0.24, 95% CI [− 0.5 to 0.04], p-value 0.09). Conclusion: We found 30–50% higher TB case fatality for males in Europe. Except for homelessness, migration, and a trend for some comorbidities, assessing effect modification could not reduce our meta-analysis' high heterogeneity. Public health authorities should take heed of this higher risk of dying in male patients' treatment services. [ABSTRACT FROM AUTHOR]

The research aims to analyze the differences between male and female employment in Turkey between 2007 and 2022. In this process, various variables are taken into account and the results are supported by TUIK (Turkish Statistical Institute) data. In this study, panel data of TUIK for the years 2007-2022 were used as the methodology. These data were analyzed using SPSS 22 and E-Views programs using Correlation, Anova, Independent Samples t test, Man-Whitney u test and Regression tests. At the end of the analysis, it was seen that there is a high degree of correlation between female and male employment and that there is a high level of difference in terms of employment in all female age groups. According to the regression analysis results, female employment grows by 0.28 units per year, while male employment grows by 0.11 units per year. This shows that female employment has been rising faster than male employment in recent years. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the relationship between low back, hamstring, and ankle flexibility with rowing performance. The study included 26 male rowers (mean age: 16.72±0.73 years). All participants were assessed regarding the flexibility of the low back, hamstring, ankle, and rowing performance by sit and reach (Baltaci et al., 2003), weight-bearing lunge (Powden et al., 2015)., and 2000-m rowing ergometer performance time tests (Mikulić et al., 2009), respectively. No correlation was found between sit and reach and 2000-m rowing ergometer performance time test results. However, a negative correlation was found between ankle flexibility and 2000-m rowing ergometer performance time test results (r= -0.39; p <0.05). Additionally, 2000-m rowing ergometer performance time test result was negatively correlated with anthropometric variables and the training frequency of rowers in a week. The stepwise multiple regression analysis results indicated that only training frequency had a significant impact on the outcome variable. Conversely, weight, height, and ankle flexibility were insignificant predictors in the analysis (R2 = .492; R = .39, p<0.05). The training frequency plays a crucial role in influencing the outcome variable. Other factors, such as weight, height, and ankle flexibility, did not demonstrate significant associations. However, it is essential to note that the regression model only takes into account a medium level of variance. Future studies may examine the potential impact of other risk factors. [ABSTRACT FROM AUTHOR]

Objective: To map Greek academic otolaryngologists, and assess gender, age and location-related differences in their rank and academic productivity. Methods: A pre-established database of local and diaspora scientists was used, after adjustment and updating for otolaryngology. The following data were recorded: age, gender, academic rank, country of work, total citations and h-index of December 2022. Results: A total of 276 Greek academic otolaryngologists were identified in the Scopus database. Of Greek otolaryngologists, 15.9 per cent are women. Of all academic otolaryngologists, 27.1 per cent have a university post, but only 4 per cent of them are women. There is an almost linear correlation between university post ranking and citations. Otolaryngologists based in Greece accounted for 3 out of the 10 most cited Greek otolaryngologists. Conclusion: There are significant age, gender and location-related differences in academic output. The representation of women and the full use of their potential in medicine require proactive measures, to lift the burdens limiting their participation. [ABSTRACT FROM AUTHOR]

PurposeActive surveillance (AS) for grade group (GG) 2 patients is not yet well defined. We sought to compare clinical outcomes of men with GG1 and GG2 prostate cancer undergoing AS in a large prospective North American cohort.Materials and methodsParticipants were prospectively enrolled in an AS study with protocol-directed followup at 10 centers in the U.S. and Canada. We evaluated time from diagnosis to biopsy grade reclassification and time to treatment. In men treated after initial surveillance, adverse pathology and recurrence were also analyzed.ResultsAt diagnosis, 154 (9%) had GG2 and 1,574 (91%) had GG1. Five-year reclassification rates were similar between GG2 and GG1 (30% vs 37%, p=0.11). However, more patients with GG2 were treated at 5 years (58% vs 34%, p

Hepatic steatosis (HS) is a growing problem in adults worldwide, with racial/ethnic disparity in the prevalence of the disease. The purpose of this study was to characterize the racial/ethnic prevalence of the stages (normal/mild [S0/S1], moderate [S2], and severe [S3]) of HS in Mexican Americans and other Hispanics compared to other racial/ethnic groups. We analyzed data for 5,492 individuals 12 years and older from the newly released National Health and Nutrition Examination Survey 2017-2018, which is a representative sample of the US adult population. HS was diagnosed by FibroScan using controlled attenuation parameter values: S0, 290. We analyzed the data using the bivariate chi-squared test and multinomial regression. The prevalence of HS overall was 46.9% (S2,16.6%; S3, 30.3%). The prevalence of S3 was highest among Mexican Americans (42.8%), lowest among Blacks (21.6%), 27.6% in other Hispanics, and 30.6% in Whites (P

BackgroundEarly evaluations of healthcare professional (HCP) COVID-19 risk occurred during insufficient personal protective equipment and disproportionate testing, contributing to perceptions of high patient-care related HCP risk. We evaluated HCP COVID-19 seropositivity after accounting for community factors and coworker outbreaks.MethodsPrior to universal masking, we conducted a single-center retrospective cohort plus cross-sectional study. All HCP (1) seen by Occupational Health for COVID-like symptoms (regardless of test result) or assigned to (2) dedicated COVID-19 units, (3) units with a COVID-19 HCP outbreak, or (4) control units from 01/01/2020 to 04/15/2020 were offered serologic testing by an FDA-authorized assay plus a research assay against 67 respiratory viruses, including 11 SARS-CoV-2 antigens. Multivariable models assessed the association of demographics, job role, comorbidities, care of a COVID-19 patient, and geocoded socioeconomic status with positive serology.ResultsOf 654 participants, 87 (13.3%) were seropositive; among these 60.8% (N = 52) had never cared for a COVID-19 patient. Being male (OR 1.79, CI 1.05-3.04, p = 0.03), working in a unit with a HCP-outbreak unit (OR 2.21, CI 1.28-3.81, p

BackgroundHealth care organizations strive to improve patient care experiences. Some use one-on-one provider counseling (shadow coaching) to identify and target modifiable provider behaviors.ObjectiveWe examined whether shadow coaching improves patient experience across 44 primary care practices in a large urban Federally Qualified Health Center.Research designSeventy-four providers with "medium" (ie, slightly below average) overall provider ratings received coaching and were compared with 246 uncoached providers. We fit mixed-effects regression models with random effects for provider (level of treatment assignment) and fixed effects for time (linear spline with a knot and "jump" at coaching date), patient characteristics and site indicators. By design, coached providers performed worse at selection; models account for the very small (0.2 point) regression-to-the-mean effects. We assessed differential effects by coach.SubjectsA total of 46,452 patients (from 320 providers) who completed the Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) Visit Survey 2.0.MeasuresCAHPS overall provider rating and provider communication composite (scaled 0-100).ResultsProviders not chosen for coaching had a nonsignificant change in performance during the period when selected providers were coached. We observed a statistically significant 2-point (small-to-medium) jump among coached providers after coaching on the CAHPS overall provider rating and provider communication score. However, these gains disappeared after 2.5 years; effects differed by coach.ConclusionsShadow coaching improved providers' overall performance and communication immediately after being coached. Regularly planned shadow coaching "booster" sessions might maintain or even increase the improvement gained in patient experience scores, but research examining additional coaching and optimal implementation is needed.

This study was conducted to investigate the long-term survival in male patients with systemic lupus erythematosus (SLE) and its predictors. The main demographic and clinical manifestations at the time of disease diagnosis were recorded retrospectively. Kaplan–Meier curves were used to calculate survival rates. Predictors of mortality were determined by backward Cox regression analysis. Eighty-four male patients with SLE were enrolled. During the 23-year study period, 11 patients died. Lupus nephritis (5 cases), infections (5 cases) and alveolar hemorrhage (1 case) were the most common causes of deaths. Overall survival rates at the end of 5, 10, 15, and 20 years after SLE disease diagnosis were 86%, 84%, 84% and 84%, respectively. In multivariate backward-regression analysis, the main determinants of death at the time of SLE diagnosis were oral ulcer (p = 0.004, HR = 7.69, 95% CI 1.92–33.33), thrombocytopenia (p = 0.012, HR = 5, 95% CI 1.41–16.66) and SLE disease activity index (SLEDAI, p = 0.05, HR = 1.08, 95% CI = 0.999–1.1). Observing oral ulcer, thrombocytopenia and high SLEDAI at the time of disease diagnosis were the main prognostic factors in male lupus patients. [ABSTRACT FROM AUTHOR]

Few studies have investigated the experience of male carers of people with dementia and fewer specifically examined whether male and female carers of people with dementia differ in their approach to the caring role. As such, this research set-out to investigate whether male carers of people with dementia approach the caring role differently to female carers. Data from 167 survey participants (24 males and 143 females) were analysed using a mixed research methodology. Participants' demographics and scores on standardised burden and coping scales were analysed using linear regression. Participants' written responses to open-ended questions were analysed using thematic analysis anchored in theories of hegemonic masculinity. No significant gender differences were identified in carers' coping strategies or self-reported carer burden. However, qualitative analysis revealed strong thematic gender differences like: gendered barriers to help-seeking; gendered service preference; gendered considerations about residential care; gendered expression of burden; and themes of the absent son and exhausted daughter. This research identified that male carers of people with dementia approach help-seeking differently to female carers, typically focusing on addressing functional tasks and refraining from showing emotions, this despite reporting similar carer burden. Rapport building with male carers should start with conversations around functional issues rather than assessing the emotional impact of the caring role. The findings reinforce the need for more qualitative research into the unmet needs of male carers of people with dementia, to inform the design of male-friendly interventions which could facilitate timely access to services by male carers. [ABSTRACT FROM AUTHOR]

Background: Previous studies examined the effects of obesity on sperm parameters and reported inconsistent results. Thus, the present study aimed to evaluate the association between obesity and the quality of sperm parameters in infertile men. Material and methods: The present cross-sectional study evaluated 218 infertile men aged 20–50. To this end, the 168-item food frequency questionnaire (FFQ) was utilized to evaluate dietary intake. The anthropometric and biochemical variables were examined using standard methods. Further, the association between obesity and the quality of sperm parameters was evaluated using the controlled linear regression for potential confounders. Results: The normal sperm morphology had a significant inverse association with BMI [adjusted β − 0.074, CI (− 0.141 to − 0.008), P = 0.029] and WC [adjusted β − 0.026, CI (− 0.051 to − 0.001), P = 0.038]. Additionally, visceral fat had a marginal inverse association with normal sperm morphology [adjusted β − 0.065, CI (− 0.138 to 0.008), P = 0.079] and non-progressive sperm motility [adjusted β − 0.241, CI (− 0.495 to 0.014), P = 0.063]. Conclusion: Even though the present results indicated that obesity, abdominal obesity, and visceral fat had inverse associations with normal sperm morphology, more mechanism-based studies should be conducted to confirm these findings. [ABSTRACT FROM AUTHOR]

ObjectiveTo utilize, in an individual and institutional privacy-preserving manner, electronic health record (EHR) data from 202 hospitals by analyzing answers to COVID-19-related questions and posting these answers online.Materials and methodsWe developed a distributed, federated network of 12 health systems that harmonized their EHRs and submitted aggregate answers to consortia questions posted at https://www.covid19questions.org. Our consortium developed processes and implemented distributed algorithms to produce answers to a variety of questions. We were able to generate counts, descriptive statistics, and build a multivariate, iterative regression model without centralizing individual-level data.ResultsOur public website contains answers to various clinical questions, a web form for users to ask questions in natural language, and a list of items that are currently pending responses. The results show, for example, that patients who were taking angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, within the year before admission, had lower unadjusted in-hospital mortality rates. We also showed that, when adjusted for, age, sex, and ethnicity were not significantly associated with mortality. We demonstrated that it is possible to answer questions about COVID-19 using EHR data from systems that have different policies and must follow various regulations, without moving data out of their health systems.Discussion and conclusionsWe present an alternative or a complement to centralized COVID-19 registries of EHR data. We can use multivariate distributed logistic regression on observations recorded in the process of care to generate results without transferring individual-level data outside the health systems.

PurposeThough utilization of medical procedures has been shown to vary considerably across the United States, similar efforts to characterize variation in the delivery of radiation therapy (RT) procedures have not been forthcoming. Our aim was to characterize variation in the delivery of common RT procedures in the Medicare population. We hypothesized that delivery would vary significantly based on provider characteristics.MethodsThe Centers for Medicare and Medicaid Services (CMS) Physician and Other Supplier Public Use File was linked to the CMS Physician Compare (PC) database by physician NPI to identify and sum all treatment delivery charges submitted by individual radiation oncologists in the non-facility-based (NFB) setting in 2016. Multivariable logistic regression analysis was carried out to determine provider characteristics (gender, practice rurality, practice region, and years since graduation) that predicted for the delivery of 3D conformal RT (3DCRT), intensity modulated RT (IMRT), stereotactic body RT (SBRT), stereotactic radiosurgery (SRS), low dose rate (LDR) brachytherapy, and high dose rate (HDR) brachytherapy delivery in the Medicare patient population. The overall significance of categorical variables in the multivariable logistic regression model was assessed by the likelihood ratio test (LRT).ResultsIn total, 1,802 physicians from the NFB practice setting were analyzed. Male gender predicted for greater LDR brachytherapy delivery (OR 8.19, 95% CI 2.58-26.05, p

BackgroundEvidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.MethodsWe performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.ResultsData were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.ConclusionsWe found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

Are women more likely to quit politics after losing their first race than men? Women's first-time candidacies skyrocketed in the wake of the 2016 presidential election. Yet we have little sense of the long-term impact of this surge in women candidates on women's representation writ large: Inexperienced candidates are more likely to lose, and women might be especially discouraged by a loss. This might make the benefits of such a surge in candidacies fleeting. Using a regression discontinuity design and data that feature 212,805 candidates across 22,473 jurisdictions between 1950 and 2018, we find that women who narrowly lose these elections are no more likely to quit politics than men who narrowly lose. Drawing on scholarship on women's lower political ambition, we interpret these findings to mean that women's decision-making differs from men's at the point of entry into politics-not at the point of reentry.

Growth and differentiation factor 15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1), may act as both a tumor suppressor and promotor and, by regulating NF-κB and macrophage signaling, promote early prostate carcinogenesis. To determine whether expression of these two inflammation-related proteins affect prostate cancer susceptibility, dual immunostaining of benign prostate biopsies for GDF-15 and NF-κB was done in a study of 503 case-control pairs matched on date, age, and race, nested within a historical cohort of 10,478 men. GDF-15 and NF-κB expression levels were positively correlated (r = 0.39; p

BACKGROUND: Light at night (LAN) inhibits nighttime secretion of melatonin and may cause circadian disruption, which may be a risk factor for cancer. Recent studies have linked high LAN exposure with elevated breast cancer risk. Given that breast cancer may share a common hormone-dependent etiology with thyroid cancer and that circadian rhythms play a role in regulating thyroid function, the authors hypothesized that exposure to LAN is positively associated with thyroid cancer incidence. METHODS: This study examined the association between LAN and thyroid cancer incidence in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. LAN exposure was estimated from satellite data and was linked to residential addresses at the baseline. Incident thyroid cancer cases were ascertained via linkage to state cancer registries. Cox regression was used to determine the relationship between LAN and thyroid cancer risk, with adjustments made for sociodemographic, lifestyle, and other environmental factors. RESULTS: Among 464,371 participants, a positive association was found between LAN and thyroid cancer risk. Specifically, in comparison with the lowest quintile of LAN, the highest quintile was associated with a 55% increase in risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.18-2.02). The association was primarily driven by papillary thyroid cancer and was stronger in women (HR, 1.81; 95% CI, 1.26-2.60) than men (HR, 1.29; 95% CI, 0.86-1.94). In women, the association was stronger for localized cancer, whereas in men, the association was stronger for a more advanced stage. Results were consistent across different tumor sizes. CONCLUSIONS: LAN was positively associated with thyroid cancer risk. Future studies are needed to confirm this association and identify underlying biological mechanisms.

Mild, blast-induced traumatic brain injury (mbTBI) is a common combat brain injury characterized by typically normal neuroimaging findings, with unpredictable future cognitive recovery. Traditional methods of electroencephalography (EEG) analysis (e.g., spectral analysis) have not been successful in detecting the degree of cognitive and functional impairment in mbTBI. We therefore collected resting state EEG (5 minutes, 64 leads) from twelve patients with a history of mbTBI, along with repeat neuropsychological testing (D-KEFS Tower test) to compare two new methods for analyzing EEG (multifractal detrended fluctuation analysis (MF-DFA) and information transfer modeling (ITM)) with spectral analysis. For MF-DFA, we extracted relevant parameters from the resultant multifractal spectrum from all leads and compared with traditional power by frequency band for spectral analysis. For ITM, because the number of parameters from each lead far exceeded the number of subjects, we utilized a reduced set of 10 leads which were compared with spectral analysis. We utilized separate 30 second EEG segments for training and testing statistical models based upon regression tree analysis. ITM and MF-DFA models both generally had improved accuracy at correlating with relevant measures of cognitive performance as compared to spectral analytic models ITM and MF-DFA both merit additional research as analytic tools for EEG and cognition in TBI.

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population. The purpose of this manuscript is to describe both the challenges and opportunities when conducting military-relevant TBI research and introduce the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Military Brain Injury working group. ENIGMA is a worldwide consortium focused on improving replicability and analytical power through data sharing and collaboration. In this paper, we discuss challenges affecting efforts to aggregate data in this patient group. In addition, we highlight how "big data" approaches might be used to understand better the role that each of these variables might play in the imaging and functional phenotypes of TBI in Service member and Veteran populations, and how data may be used to examine important military specific issues such as return to duty, the late effects of combat-related injury, and alteration of the natural aging processes.

BackgroundIt is unknown whether a positive serology result correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value of SARS-CoV-2 serology tests, especially when testing populations with low disease prevalence.MethodsA neutralization assay was validated in a set of PCR-confirmed positive specimens and in a negative cohort. In addition, 9530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N = 164 individuals) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and neutralizing activity was determined. Neutralizing antibody titers (50% inhibitory dilution, ID50) were also longitudinally monitored in patients confirmed to have SARS-CoV-2 by PCR.ResultsThe SARS-CoV-2 neutralization assay had a positive percentage agreement (PPA) of 96.6% with a SARS-CoV-2 PCR test and a negative percentage agreement (NPA) of 98.0% across 100 negative control individuals. ID50 neutralization titers positively correlated with all 3 clinical serology platforms. Longitudinal monitoring of hospitalized PCR-confirmed patients with COVID-19 demonstrated they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2 and 78.4%, respectively.ConclusionsThese 3 clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in patients with COVID-19. All patients confirmed SARS-CoV-2 positive by PCR develop neutralizing antibodies.

IntroductionThe outcomes of transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with hepatic encephalopathy (HE) are controversial. We studied the relationship of pre-TIPS HE in patients undergoing TIPS for refractory ascites on all-cause mortality and development of post-TIPS HE.MethodsA single-center retrospective comparison study was performed for patients undergoing TIPS for refractory ascites. Survival by history of pre-TIPS HE was demonstrated with Kaplan-Meier curves. Univariate and multivariate logistic regression analyses were performed to identify the predictors of post-TIPS clinical outcomes for patients with and without pre-TIPS HE.ResultsWe identified 202 TIPS recipients (61% male, mean ± SD; age 59.1 ± 10.2 years; mean model for end-stage liver disease score 17.3 ± 6.9). Pre-TIPS HE did not predispose patients for increased all-cause mortality, increased risk of experiencing HE within 60 days, or increased risk of hospital admission for HE within 6 months. A multivariate analysis demonstrated that total bilirubin (odds ratio [OR] 1.03; P = 0.016) and blood urea nitrogen (OR 1.15; P = 0.002) were predictors for all-cause mortality within 6 months post-TIPS. Age ≥65 years (OR 3.92; P = 0.004), creatinine (OR 2.22; P = 0.014), and Child-Pugh score (OR 1.53; P = 0.006) were predictors for HE within 60 days post-TIPS. Predictors of intensive care admission for HE within 6 months post-TIPS included age ≥65 years (OR 8.84; P = 0.018), history of any admission for HE within 6 months pre-TIPS (OR 8.42; P = 0.017), and creatinine (OR 2.22; P = 0.015).DiscussionIf controlled, pre-TIPS HE does not adversely impact patient survival or clinical outcomes, such as development of HE within 60 days of TIPS or hospital admission for HE within 6 months. Patients may be able to undergo TIPS for refractory ascites despite a history of HE.

BackgroundAge-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer's disease (AD), although their interactive effects have yet to be fully examined.ObjectiveThe current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI).MethodsThis study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1-42 (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified.ResultsMultiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ42 (B = -1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s

ObjectivesVeterans Health Administration encourages auricular acupuncture (Battlefield Acupuncture/BFA) as a nonpharmacologic approach to pain management. Qualitative reports highlighted a "gateway hypothesis": providing BFA can lead to additional nonpharmacologic treatments. This analysis examines subsequent use of traditional acupuncture.Research designCohort study of Veterans treated with BFA and a propensity score matched comparison group with a 3-month follow-up period to identify subsequent use of traditional acupuncture. Matching variables included pain, comorbidity, and demographics, with further adjustment in multivariate regression analysis.SubjectsWe identified 41,234 patients who used BFA across 130 Veterans Health Administration medical facilities between October 1, 2016 and March 31, 2019. These patients were matched 2:1 on Veterans who used VA care but not BFA during the same period resulting in a population of 24,037 BFA users and a comparison cohort of 40,358 non-BFA users. Patients with prior use of traditional acupuncture were excluded.ResultsAmong Veterans receiving BFA, 9.5% subsequently used traditional acupuncture compared with 0.9% of non-BFA users (P

People living with HIV (PLWH) experience chronic pain that may impact function. Gaps in knowledge exist for factors that impact pain and pain medication use in older (age 50+) PLWH. Data for this study were obtained from the Aging with Dignity, Health, Optimism and Community (ADHOC) cohort, an observational study of older PLWH from 10 clinics across the United States. Participants self-reported socioeconomic, psychosocial, and health factors via an online questionnaire. Of 1,051 participants, 66% reported pain. In a multivariable regression model, multimorbidity and tobacco use were associated with a greater likelihood of experiencing pain, whereas being male, black, and having higher cognitive function were associated with a lower likelihood of experiencing pain. Of the 696 participants who reported pain, 46% reported using pain medication. In a multivariable regression model, pain medication use was associated with multimorbidity and with lower income. Recognition of the factors associated with pain and pain medication use in this vulnerable population may lead to strategies that mitigate negative health outcomes.

BACKGROUND: Cleft lip and palate patients undergo a significant number of interventions during their childhood and adolescence. Although the intention of such interventions is to improve psychosocial functioning, there exists a paucity of data on the psychosocial outcomes of the burden of care on cleft children. In this work, the long-term effects of quantity and timing of childhood operations on teenagers with cleft lip and palate were evaluated. METHODS: Cleft lip and palate patients (aged 14 to 17 years; n = 55) and an age-matched unaffected cohort (n = 14) prospectively enrolled from two institutions were administered the anger, anxiety, and depressive symptoms instruments from the Pediatric Patient-Reported Outcomes Measurement Information System. Total number of operations and operations stratified by age groups (0 to 7, 8 to 10, 11 to 13, and 14 to 17 years) were evaluated in relationship to instrument scores. Descriptive statistics, independent t tests, Pearson correlations, and multiple linear regression analyses were conducted. RESULTS: No differences in overall psychosocial functioning were found between the cleft lip and palate and comparison groups. Total quantity of childhood operations did not correlate to psychosocial functioning of cleft lip and palate teenagers. However, multiple linear regression analyses demonstrated that increased number of operations in the 8- to 10-year-old age range predicted increased anxiety and depressive symptoms in teenagers (β = 0.38, p = 0.009; and β = 0.29, p = 0.03, respectively). CONCLUSIONS: It was previously reported by the authors group that the 8- to 10-year-old age range is an at-risk period for psychosocial distress in children with craniofacial anomalies. Their current work demonstrates that increased number of operations during this time frame may result in long-term consequences in anxiety and depression in cleft lip and palate patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Large amounts of resources are spent annually to improve educational achievement and to close the gender gap in sciences with typically very modest effects. In 2010, a 15-min self-affirmation intervention showed a dramatic reduction in this gender gap. We reanalyzed the original data and found several critical problems. First, the self-affirmation hypothesis stated that women's performance would improve. However, the data showed no improvement for women. There was an interaction effect between self-affirmation and gender caused by a negative effect on men's performance. Second, the findings were based on covariate-adjusted interaction effects, which imply that self-affirmation reduced the gender gap only for the small sample of men and women who did not differ in the covariates. Third, specification-curve analyses with more than 1,500 possible specifications showed that less than one quarter yielded significant interaction effects and less than 3% showed significant improvements among women.

BackgroundSchizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.MethodsHippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.ResultsThis study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = -0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = -0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10-8, 95% CI 7.0-14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.ConclusionsThis study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.

PurposeOlder patients undergoing radiation therapy (RT) for pelvic malignancies are at increased risk for pelvic fracture, which is associated with significant morbidity and mortality. RT techniques such as brachytherapy or intensity modulated RT (IMRT) allow for more conformal dose distributions, but it is not known whether the risk for pelvic fracture varies by RT modality.Methods and materialsThis observational cohort study involved 28,354 patients ≥65 years old, treated with RT for pelvic malignancies. We evaluated the relative risk of pelvic fracture by type of RT when accounting for baseline factors. To test for nonspecific effects, we also evaluated risk of nonpelvic fractures in the same population.ResultsThe 5-year incidence of pelvic fractures was 12.7% (95% confidence interval [CI], 11.6%-13.8%), 11.8% (10.8%-12.8%), and 3.7% (3.4%-4.0%) for patients with gastrointestinal, gynecologic, and prostate cancer, respectively. On multivariable analysis, being treated with IMRT (hazard ratio, 0.85; 95% CI, 0.73-0.99) or brachytherapy therapy alone (hazard ratio, 0.43; 95% CI, 0.34-0.54) was associated with a reduced hazard for pelvic fractures compared with 3D conformal radiation therapy in female patients. In contrast, there was no association with RT modality and the hazard for nonpelvic fractures among females. There was no significant association between pelvic fractures and IMRT or brachytherapy for male patients. White race, advanced age, and higher comorbidity were associated with an increased hazard for pelvic fracture.ConclusionsIMRT and brachytherapy were associated with a reduced risk of pelvic fractures in older women undergoing RT for pelvic malignancies. Pelvic insufficiency fracture risk should be considered when treating with pelvic RT.

ObjectiveSelf-harm rates among U.S. adolescents have risen substantially. Health and social outcomes among contemporary self-harming youths are infrequently tracked and poorly understood. This study investigated long-term health service utilization (emergency department [ED] visits and inpatient admissions) and inpatient costs among a recent cohort of adolescents with deliberate self-harm.MethodsThis retrospective cohort study used statewide, all-payer, longitudinally linked discharge data from California. All residents ages 10-19 presenting to EDs in 2010 with deliberate self-harm (N=5,396) were compared with two control groups: a random sample of adolescent ED patients with other complaints, matched on sex, age, residential zip code, and month of index visit (general control patients, N=14,921), and matched ED patients with psychiatric complaints but no self-harm (psychiatric control patients, N=15,835). Outcomes included 5-year rates of ED visits, inpatient admissions, and inpatient costs, overall and for psychiatric and nonpsychiatric complaints separately.ResultsSelf-harm patients' ED use, inpatient admissions, and inpatient costs were significantly higher than those of general control patients (by 39%, 81%, and 21%, respectively), when the analysis controlled for confounding demographic and utilization characteristics. Associations mostly persisted, although smaller in magnitude, in comparisons between self-harm and psychiatric control patients. Psychiatric and nonpsychiatric complaints contributed to self-harming adolescents' excess health service utilization and costs.ConclusionsDeliberate self-harm among adolescents was found to be associated with long-lasting and costly patterns of health service utilization, often but not exclusively for psychiatric complaints. Future research should investigate the pathways underlying these associations and incorporate service utilization as a key patient outcome.

One simple marshmallow test in preschool children predicts an array of important life outcomes, according to multiple studies spanning several decades. However, a recent conceptual replication casts doubt on these famous findings. We conducted an independent, preregistered secondary analysis to test whether previously observed longitudinal associations between preschool delay of gratification and adolescent outcomes would be conceptually replicated. Associations were significant for three of the five outcomes we tested using the analytic approach employed in the original studies of the marshmallow test. Relationships between delay of gratification and problem behavior held in bivariate, multivariate, and multilevel models; in contrast, no significant relationships between delay and problem behavior were found in the other recent replication, even though both studies used the same data set. These relationships were better explained by social support than by self-control, suggesting that the marshmallow test is predictive because it reflects aspects of a child's early environment that are important over the long term. This novel interpretation of the classic findings points to new directions for intervention.

There is increasing awareness that self-reported sleep abnormalities are negatively associated with brain structure and function in older adults. Less is known, however, about how objectively measured sleep associates with brain structure. We objectively measured at-home sleep to investigate how sleep architecture and sleep quality related to white matter microstructure in older adults. 43 cognitively normal, older adults underwent diffusion tensor imaging (DTI) and a sleep assessment within a six-month period. Participants completed the PSQI, a subjective measure of sleep quality, and used an at-home sleep recorder (Zeo, Inc.) to measure total sleep time (TST), sleep efficiency (SE), and percent time in light sleep (LS), deep sleep (DS), and REM sleep (RS). Multiple regressions predicted fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum as a function of total PSQI score, TST, SE, and percent of time spent in each sleep stage, controlling for age and sex. Greater percent time spent in RS was significantly associated with higher FA (β = 0.41, p = 0.007) and lower MD (β = -0.30, p = 0.03). Total PSQI score, TST, SE, and time spent in LS or DS were not significantly associated with FA or MD (p>0.13). Percent time spent in REM sleep, but not quantity of light and deep sleep or subjective/objective measures of sleep quality, positively predicted white matter microstructure integrity. Our results highlight an important link between REM sleep and brain health that has the potential to improve sleep interventions in the elderly.

OBJECTIVE: To evaluate the association of ibuprofen exposure with the risk of bronchopulmonary dysplasia (BPD) in extremely premature infants. STUDY DESIGN: This was a retrospective study of all extremely premature infants admitted to a tertiary unit from 2016 to 2018. RESULTS: A total of 203 extremely premature infants were included in this study. The rate of BPD was significantly higher in infants with early exposure to ibuprofen (42.5%) compared to infants with no exposure (21.6%, P = 0.001). After adjusting for covariates, the risk of BPD was associated independently with ibuprofen exposure (odds ratios (OR) 2.296, 95% confidence interval (CI): 1.166-4.522, p = 0.016). Further analysis showed a trend towards higher risk of BPD in infants with successful patent ductus arteriosus (PDA) closure after ibuprofen treatment (32.3%) compared to non-treated infants (20.2%, p = 0.162). CONCLUSION: Our findings suggest that ibuprofen exposure may contribute to the occurrence of BPD in extremely preterm infants.

BackgroundTo apply a novel method to adjust for HIV knowledge as an unmeasured confounder for the effect of unsafe injection on future HIV testing.MethodsThe data were collected from 601 HIV-negative persons who inject drugs (PWID) from a cohort in San Francisco. The panel-data generalized estimating equations (GEE) technique was used to estimate the adjusted risk ratio (RR) for the effect of unsafe injection on not being tested (NBT) for HIV. Expert opinion quantified the bias parameters to adjust for insufficient knowledge about HIV transmission as an unmeasured confounder using Bayesian bias analysis.ResultsExpert opinion estimated that 2.5%-40.0% of PWID with unsafe injection had insufficient HIV knowledge; whereas 1.0%-20.0% who practiced safe injection had insufficient knowledge. Experts also estimated the RR for the association between insufficient knowledge and NBT for HIV as 1.1-5.0. The RR estimate for the association between unsafe injection and NBT for HIV, adjusted for measured confounders, was 0.96 (95% confidence interval: 0.89,1.03). However, the RR estimate decreased to 0.82 (95% credible interval: 0.64, 0.99) after adjusting for insufficient knowledge as an unmeasured confounder.ConclusionOur Bayesian approach that uses expert opinion to adjust for unmeasured confounders revealed that PWID who practice unsafe injection are more likely to be tested for HIV - an association that was not seen by conventional analysis.

The aim of time-varying heart rate variability spectral analysis is to detect and quantify changes in the heart rate variability spectrum components during nonstationary events. Of the methods available, the nonparametric short-time Fourier Transform and parametric time-varying autoregressive modeling are the most commonly employed. The current study (1) compares short-time Fourier Transform and autoregressive modeling methods influence on heart rate variability spectral characteristics over time and during an experimental ozone exposure in mature adult spontaneously hypertensive rats, (2) evaluates the agreement between short-time Fourier Transform and autoregressive modeling method results, and (3) describes the advantages and disadvantages of each method. Although similar trends were detected during ozone exposure, statistical comparisons identified significant differences between short-time Fourier Transform and autoregressive modeling analysis results. Significant differences were observed between methods for LF power (p ≤ 0.014); HF power (p ≤ 0.011); total power (p ≤ 0.027); and normalized HF power (p = 0.05). Furthermore, inconsistencies between exposure-related observations accentuated the lack of agreement between short-time Fourier Transform and autoregressive modeling overall. Thus, the short-time Fourier Transform and autoregressive modeling methods for time-varying heart rate variability analysis could not be considered interchangeable for evaluations with or without interventions that are known to affect cardio-autonomic activity.

BackgroundIrritable bowel syndrome (IBS) is a stress-sensitive disorder of brain-gut interactions associated with a higher prevalence of early adverse life events (EALs). However, it is incompletely understood how trauma severity or disclosure influence the risk of developing IBS or symptom severity.AimsTo determine whether (1) IBS patients report a greater number of EALs compared with healthy controls; (2) trauma severity and first age of EAL increase the odds of IBS; (3) confiding in others reduces the odds of IBS; (4) the number, trauma severity, and first age of EAL are associated with symptom severity; (5) sex differences exist.MethodsIn total, 197 IBS patients (72% women, mean age=30.28 y) and 165 healthy controls (59% women, mean age=30.77 y) completed the Childhood Traumatic Events Scale, measuring severity of EALs and degree of confiding in others. Regression analyses were used to predict IBS status from EALs and association between gastrointestinal symptoms and EALs.ResultsA greater number of EALs [odds ratio (OR)=1.36, 95% confidence interval (CI), 1.14-1.62; P

ObjectiveTo assess the impact of a newly developed Central-Line Insertion Site Assessment (CLISA) score on the incidence of local inflammation or infection for CLABSI prevention.DesignA pre- and postintervention, quasi-experimental quality improvement study.Setting and participantsAdult inpatients with central venous catheters (CVCs) hospitalized in an intensive care unit or oncology ward at a large academic medical center.MethodsWe evaluated CLISA score impact on insertion site inflammation and infection (CLISA score of 2 or 3) incidence in the baseline period (June 2014-January 2015) and the intervention period (April 2015-October 2017) using interrupted times series and generalized linear mixed-effects multivariable analyses. These were run separately for days-to-line removal from identification of a CLISA score of 2 or 3. CLISA score interrater reliability and photo quiz results were evaluated.ResultsAmong 6,957 CVCs assessed 40,846 times, percentage of lines with CLISA score of 2 or 3 in the baseline and intervention periods decreased by 78.2% (from 22.0% to 4.7%), with a significant immediate decrease in the time-series analysis (P < .001). According to the multivariable regression, the intervention was associated with lower percentage of lines with a CLISA score of 2 or 3, after adjusting for age, gender, CVC body location, and hospital unit (odds ratio, 0.15; 95% confidence interval, 0.06-0.34; P < .001). According to the multivariate regression, days to removal of lines with CLISA score of 2 or 3 was 3.19 days faster after the intervention (P < .001). Also, line dwell time decreased 37.1% from a mean of 14 days (standard deviation [SD], 10.6) to 8.8 days (SD, 9.0) (P < .001). Device utilization ratios decreased 9% from 0.64 (SD, 0.08) to 0.58 (SD, 0.06) (P = .039).ConclusionsThe CLISA score creates a common language for assessing line infection risk and successfully promotes high compliance with best practices in timely line removal.

Impaired single breath carbon monoxide diffusing capacity (DLCO) is associated with emphysema. Small airways disease (SAD) may be a precursor lesion to emphysema, but the relationship between SAD and DLCO is undescribed. We hypothesized that in mild COPD, functional SAD (fSAD) defined by computed tomography (CT) and Parametric Response Mapping methodology would correlate with impaired DLCO. Using data from ever-smokers in the COPDGene cohort, we established that fSAD correlated significantly with lower DLCO among both non-obstructed and GOLD 1-2 subjects. The relationship between DLCO with CT-defined emphysema was present in all GOLD stages, but most prominent in severe disease. TRIAL REGISTRATION: NCT00608764. Registry: COPDGene. Registered 06 February 2008, retrospectively registered.

(1) Background: There appears to be a growing disconnection between humans and their natural environments which has been linked to poor mental health and ecological destruction. Previous research suggests that individual levels of nature relatedness can be increased through the use of classical psychedelic compounds, although a causal link between psychedelic use and nature relatedness has not yet been established. (2) Methods: Using correlations and generalized linear mixed regression modelling, we investigated the association between psychedelic use and nature relatedness in a prospective online study. Individuals planning to use a psychedelic received questionnaires 1 week before (N = 654), plus one day, 2 weeks, 4 weeks, and 2 years after a psychedelic experience. (3) Results: The frequency of lifetime psychedelic use was positively correlated with nature relatedness at baseline. Nature relatedness was significantly increased 2 weeks, 4 weeks and 2 years after the psychedelic experience. This increase was positively correlated with concomitant increases in psychological well-being and was dependent on the extent of ego-dissolution and the perceived influence of natural surroundings during the acute psychedelic state. (4) Conclusions: The here presented evidence for a context- and state-dependent causal effect of psychedelic use on nature relatedness bears relevance for psychedelic treatment models in mental health and, in the face of the current ecological crisis, planetary health.

BackgroundIntimate partner violence (IPV), HIV and sexually transmitted infections (STI) can contribute to disparities in population health, depending on the individual, social and environmental factors characterizing a setting. To better understand the place-based determinants and patterns of these key interrelated public health problems in Uganda, we compared risk factors for IPV, HIV and STI in fishing, trading and agrarian communities in Rakai, Uganda by gender.MethodThis study used cross-sectional data collected from 14,464 sexually active men (n = 6531) and women (n = 7933) as part of the Rakai Community Cohort Study, a population-based open cohort study of men and women aged 15-49 years. We used multilevel modified poisson regression models, which incorporated random intercepts for community and households. Factors associated with IPV, HIV and STI were assessed separately for men and women in fishing, trading and agrarian communities.ResultsA larger proportion of participants in the fishing communities than those in trading and agrarian communities were HIV positive, engaged in HIV risk behaviors, had STI symptoms and reported perpetration of or victimization by IPV. Female gender was a shared correlate of IPV, HIV and STI in the fishing communities. Engagement in multiple sexual relationships or partner's engagement in multiple relationships were shared correlates of IPV, and HIV in agrarian communities and IPV and STI in trading communities.ConclusionPrograms should target factors at multiple levels to reduce risk for syndemic conditions of HIV, STI and IPV in Rakai, Uganda particularly among men and women in fishing communities.

BackgroundCRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up to 16% efficiency in generating conditional knockout (cKO or floxed) alleles by microinjection of 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides as donors (referred herein as "two-donor floxing" method).ResultsWe re-evaluate the two-donor method from a consortium of 20 laboratories across the world. The dataset constitutes 56 genetic loci, 17,887 zygotes, and 1718 live-born mice, of which only 15 (0.87%) mice contain cKO alleles. We subject the dataset to statistical analyses and a machine learning algorithm, which reveals that none of the factors analyzed was predictive for the success of this method. We test some of the newer methods that use one-donor DNA on 18 loci for which the two-donor approach failed to produce cKO alleles. We find that the one-donor methods are 10- to 20-fold more efficient than the two-donor approach.ConclusionWe propose that the two-donor method lacks efficiency because it relies on two simultaneous recombination events in cis, an outcome that is dwarfed by pervasive accompanying undesired editing events. The methods that use one-donor DNA are fairly efficient as they rely on only one recombination event, and the probability of correct insertion of the donor cassette without unanticipated mutational events is much higher. Therefore, one-donor methods offer higher efficiencies for the routine generation of cKO animal models.

BackgroundInjection drug use (IDU) is associated with multiple health harms. The vast majority of IDU initiation events (in which injection-naïve persons first adopt IDU) are assisted by a person who injects drugs (PWID), and as such, IDU could be considered as a dynamic behavioral transmission process. Data suggest that opioid agonist treatment (OAT) enrollment is associated with a reduced likelihood of assisting with IDU initiation. We assessed the association between recent OAT enrollment and assisting IDU initiation across several North American settings and used dynamic modeling to project the potential population-level impact of OAT scale-up within the PWID population on IDU initiation.Methods and findingsWe employed data from a prospective multicohort study of PWID in 3 settings (Vancouver, Canada [n = 1,737]; San Diego, United States [n = 346]; and Tijuana, Mexico [n = 532]) from 2014 to 2017. Site-specific modified Poisson regression models were constructed to assess the association between recent (past 6 month) OAT enrollment and history of ever having assisted an IDU initiation with recently assisting IDU initiation. Findings were then pooled using linear mixed-effects techniques. A dynamic transmission model of IDU among the general population was developed, stratified by known factors associated with assisting IDU initiation and relevant drug use behaviors. The model was parameterized to a generic North American setting (approximately 1% PWID) and used to estimate the impact of increasing OAT coverage among PWID from baseline (approximately 21%) to 40%, 50%, and 60% on annual IDU initiation incidence and corresponding PWID population size across a decade. From Vancouver, San Diego, and Tijuana, respectively, 4.5%, 5.2%, and 4.3% of participants reported recently assisting an IDU initiation, and 49.4%, 19.7%, and 2.1% reported recent enrollment in OAT. Recent OAT enrollment was significantly associated with a 45% lower likelihood of providing recent IDU initiation assistance among PWID (relative risk [RR] 0.55 [95% CI 0.36-0.84], p = 0.006) compared to those not recently on OAT. Our dynamic model predicts a baseline mean of 1,067 (2.5%-97.5% interval [95% I 490-2,082]) annual IDU initiations per 1,000,000 individuals, of which 886 (95% I 406-1,750) are assisted by PWID. Based on our observed statistical associations, our dynamic model predicts that increasing OAT coverage from approximately 21% to 40%, 50%, or 60% among PWID could reduce annual IDU initiations by 11.5% (95% I 2.4-21.7), 17.3% (95% I 5.6-29.4), and 22.8% (95% I 8.1-36.8) and reduce the PWID population size by 5.4% (95% I 0.1-12.0), 8.2% (95% I 2.2-16.9), and 10.9% (95% I 3.2-21.8) relative to baseline, respectively, in a decade. Less impact occurs when the protective effect of OAT is diminished, when a greater proportion of IDU initiations are unassisted by PWID, and when average IDU career length is longer. The study's main limitations are uncertainty in the causal pathway between OAT enrollment and assisting with IDU initiation and the use of a simplified model of IDU initiation.ConclusionsIn addition to its known benefits on preventing HIV, hepatitis C virus (HCV), and overdose among PWID, our modeling suggests that OAT scale-up may also reduce the number of IDU initiations and PWID population size.

Rationale: The 2016 guidelines for hospital-acquired pneumonia (HAP) suggest applying a universal antibiogram resistance threshold in addition to patient criteria to determine empiric coverage. The impact of these recommendations is unknown.Objectives: 1) Describe national antibiotic use and microbiology patterns for HAP among patients with noninfectious admissions, 2) measure the predictive performance of the antibiogram threshold and risk factors, and 3) estimate the change in practice with guideline implementation.Methods: We conducted a retrospective analysis of all hospitalizations without initial infection but with secondary pneumonia diagnoses at Veterans Affairs Medical Centers between October 1, 2012, and September 30, 2015. For each hospitalization we extracted: presence of methicillin-resistant Staphylococcus aureus (MRSA) and resistant gram-negative rods (R-GNR) in cultures, anti-MRSA and antipseudomonal antimicrobial administration, and facility-level prevalence of MRSA and R-GNR. We calculated the percentage of hospitalizations with resistant organisms, broad-spectrum antibiotics, and the predictive performance of patient characteristics and prevalence thresholds for MRSA.Results: Among 3,562 cases, 5.17% were positive for MRSA and 2.30% for R-GNR. The recommended MRSA prevalence threshold was 100.00% sensitive (95% confidence interval [CI], 98.02-100.00%) and 0.03% specific (95% CI, 0.00-0.16%) for MRSA-positive culture, leading to overtreatment of 94.81% (95% CI, 94.02-95.50%) of patients. Pressor order (odds ratio [OR], 3.89; 95% CI, 1.17-12.91) and intravenous antibiotics within the past 90 days (OR, 1.98; 95% CI, 1.03-3.81) were associated with MRSA. Mechanical ventilation was associated with R-GNR (OR, 4.37; 95% CI, 1.52-12.57).Conclusions: The guideline-recommended antibiogram threshold and characteristics did not improve prediction of MRSA or R-GNR and would have led to an increase in MRSA treatment.

ObjectiveExtremely low birth weight children are at high risk for cognitive impairment.Study designCognitive outcome of extremely low birth weight children participating in a Neonatal Research Network, randomized trial was evaluated at 18 and 30 months corrected age using the Bayley Scales of Infant Development, 2nd ed. Family resources and social support were assessed using a Family Resource Scale parent questionnaire. Regression analysis was used to determine independent demographic, medical, and family resource factors influencing longitudinal cognitive outcome.ResultHigher Family Resource Scale scores at 18 months were associated with greater improvement in cognitive scores between 18 and 30 months. Cognitive outcome was most adversely affected in children whose families had the least resources and social support. The adverse effect of poor social support was independent of family income.ConclusionPoor interpersonal social support has an independent, adverse impact on cognitive outcomes of extremely low birth weight infants.

OBJECTIVES:It is unknown whether preoperative use of ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) affects the risk of acute kidney injury (AKI) after colorectal cancer (CRC) surgery. We assessed the impact of preoperative ACE-I/ARB use on risk of AKI after CRC surgery. DESIGN:Observational cohort study. Patients were divided into three exposure groups-current, former and non-users-through reimbursed prescriptions within 365 days before the surgery. AKI within 7 days after surgery was defined according to the current Kidney Disease Improving Global Outcome consensus criteria. SETTING:Population-based Danish medical databases. PARTICIPANTS:A total of 9932 patients undergoing incident CRC surgery during 2005-2014 in northern Denmark were included through the Danish Colorectal Cancer Group Database. OUTCOME MEASURE:We computed cumulative incidence proportions (risk) of AKI with 95% CIs for current, former and non-users of ACE-I/ARB, including death as a competing risk. We compared current and former users with non-users by computing adjusted risk ratios (aRRs) using log-binomial regression adjusted for demographics, comorbidities and CRC-related characteristics. We stratified the analyses of ACE-I/ARB users to address any difference in impact within relevant subgroups. RESULTS:Twenty-one per cent were ACE-I/ARB current users, 6.4% former users and 72.3% non-users. The 7-day postoperative AKI risk for current, former and non-users was 26.4% (95% CI 24.6% to 28.3%), 25.2% (21.9% to 28.6%) and 17.8% (17.0% to 18.7%), respectively. The aRRs of AKI were 1.20 (1.09 to 1.32) and 1.16 (1.01 to 1.34) for current and former users, compared with non-users. The relative risk of AKI in current compared with non-users was consistent in all subgroups, except for higher aRR in patients with a history of hypertension. CONCLUSIONS:Being a current or former user of ACE-I/ARBs is associated with an increased risk of postoperative AKI compared with non-users. Although it may not be a drug effect, users of ACE-I/ARBs should be considered a risk group for postoperative AKI.

HIV and methamphetamine (MA) use disorder are commonly comorbid and individually associated with adverse health consequences, including frailty; however, less is known about the combined effects of both conditions. The current cross-sectional study examined how HIV and lifetime MA use disorder relate to frailty and explored associations between frailty and relevant clinical outcomes (i.e., neurocognitive and everyday functioning). Participants were categorized into three groups based on HIV status and lifetime MA diagnosis: HIV+/MA+ (n = 43), HIV+/MA- (n = 75), and HIV-/MA- (n = 92). A frailty index score (representing proportion of accumulated multisystem deficits) was calculated from 27 medical and psychiatric deficits. Multiple regression was used to examine frailty index score by HIV/MA group. Additional multiple regression models examined the interaction between frailty and HIV/MA group on cognitive and everyday functioning. Comorbid HIV+/MA+ participants had higher frailty index scores than both HIV-/MA- (b = -0.13, p

Recent evidence suggests the aging process is accelerated by HIV. Degradation of white matter (WM) has been independently associated with HIV and healthy aging. Thus, WM may be vulnerable to joint effects of HIV and aging. Diffusion-weighted imaging (DWI) was conducted with HIV-seropositive (n = 72) and HIV-seronegative (n = 34) adults. DWI data underwent tractography, which was parcellated into 18 WM tracts of interest (TOIs). Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) regression was conducted assessing the joint effect of advanced age and HIV on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) along TOI fibers. In addition to main effects of age and HIV on WM microstructure, the interactive effect of age and HIV was significantly related to lower FA and higher MD, AD, and RD across all TOIs. The location of findings was consistent with the clinical presentation of HIV-associated neurocognitive disorders. While older age is related to poorer WM microstructure, its detrimental effect on WM is stronger among HIV+ relative to HIV- individuals. Loss of WM integrity in the context of advancing age may place HIV+ individuals at increased risk for brain and cognitive compromise.

BackgroundA growing proportion of Medicare beneficiaries is covered by private insurers through Medicare Advantage, yet little is known about how these plans are structured in terms of relationships with physicians and implications for quality of care.ObjectiveThe objective of this study was to assess whether greater physician concentration of services across insurers was associated with higher quality in Medicare Advantage (MA), overall and particularly among MA insurers serving a high proportion of vulnerable enrollees.Research designA retrospective cohort design with regression analysis.Data sourcesThe primary dataset was 2014 MA encounter records submitted by insurers to the Centers for Medicare and Medicaid Services, covering 600,329 physicians across 119 insurers. These data were merged with Centers for Medicare and Medicaid Services data on MA contract quality rating as well as physician characteristics in the Medicare Data on Provider Practice and Specialty file.MeasuresTwo measures were generated to capture the concentration of physician services across insurers: the percentage of a physician's Medicare services which was through MA (MA penetration); and the percentage of a physician's MA services with a specific insurer (insurer share of MA services).ResultsGreater MA penetration and insurer share of MA services were each associated with higher MA plan quality. The relationship between insurer share and quality was stronger in contracts with a relatively high percentage of disabled enrollees.ConclusionGreater physician concentration of services across MA insurers was associated with a higher quality of care overall and especially among vulnerable enrollees.

Chronic kidney disease (CKD) is a common disease of aging and increases fracture risk over advanced age alone. Aging and CKD differently impair bone turnover and mineralization. We thus hypothesize that the loss of bone quality would be greatest with the combination of advanced age and CKD. We evaluated bone from young adult (6 mo.), middle-age (18 mo.), and old (24 mo.) male C57Bl/6 mice three months following either 5/6th nephrectomy, to induce CKD, or Sham procedures. CKD exacerbated losses of cortical and trabecular microarchitecture associated with aging. Aging and CKD each resulted in thinner, more porous cortices and fewer and thinner trabeculae. Bone material quality was also reduced with CKD, and these changes to bone material were distinct from those due to age. Aging reduced whole-bone flexural strength and modulus, micrometer-scale nanoindentation modulus, and nanometer-scale tissue and collagen strain (small-angle x-ray scattering [SAXS]. By contrast, CKD reduced work to fracture and variation in bone tissue modulus and composition (Raman spectroscopy), and increased percent collagen strain. The increased collagen strain burden was associated with loss of toughness in CKD. In addition, osteocyte lacunae became smaller, sparser, and more disordered with age for Sham mice, yet these age-related changes were not clearly observed in CKD. However, for CKD, larger lacunae positively correlated with increased serum phosphate levels, suggesting that osteocytes play a role in systemic mineral homeostasis. This work demonstrates that CKD reduces bone quality, including microarchitecture and bone material properties, and that loss of bone quality with age is compounded by CKD. These findings may help reconcile why bone mass does not consistently predict fracture in the CKD population, as well as why older individuals with CKD are at high risk of fragility.

ObjectivesThis study of loneliness across adult lifespan examined its associations with sociodemographics, mental health (positive and negative psychological states and traits), subjective cognitive complaints, and physical functioning.DesignAnalysis of cross-sectional data.Participants340 community-dwelling adults in San Diego, California, mean age 62 (SD = 18) years, range 27-101 years, who participated in three community-based studies.MeasurementsLoneliness measures included UCLA Loneliness Scale Version 3 (UCLA-3), 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Social Isolation Scale, and a single-item measure from the Center for Epidemiologic Studies Depression (CESD) scale. Other measures included the San Diego Wisdom Scale (SD-WISE) and Medical Outcomes Survey- Short form 36.ResultsSeventy-six percent of subjects had moderate-high levels of loneliness on UCLA-3, using standardized cut-points. Loneliness was correlated with worse mental health and inversely with positive psychological states/traits. Even moderate severity of loneliness was associated with worse mental and physical functioning. Loneliness severity and age had a complex relationship, with increased loneliness in the late-20s, mid-50s, and late-80s. There were no sex differences in loneliness prevalence, severity, and age relationships. The best-fit multiple regression model accounted for 45% of the variance in UCLA-3 scores, and three factors emerged with small-medium effect sizes: wisdom, living alone and mental well-being.ConclusionsThe alarmingly high prevalence of loneliness and its association with worse health-related measures underscore major challenges for society. The non-linear age-loneliness severity relationship deserves further study. The strong negative association of wisdom with loneliness highlights the potentially critical role of wisdom as a target for psychosocial/behavioral interventions to reduce loneliness. Building a wiser society may help us develop a more connected, less lonely, and happier society.

Cortical bone assessment using magnetic resonance imaging (MRI) has recently received great attention in an effort to avoid the potential harm associated with ionizing radiation-based techniques. Ultrashort echo time MRI (UTE-MRI) techniques can acquire signal from major hydrogen proton pools in cortical bone, including bound and pore water, as well as from the collagen matrix. This study aimed to develop and evaluate the feasibility of a technique for mapping bound water, pore water, and collagen proton densities in human cortical bone ex vivo and in vivo using three-dimensional UTE Cones (3D-UTE-Cones) MRI. Eight human tibial cortical bone specimens (63 ± 19 years old) were scanned using 3D-UTE-Cones sequences on a clinical 3 T MRI scanner and a micro-computed tomography (μCT) scanner. Total, bound, and pore water proton densities (TWPD, BWPD, and PWPD, respectively) were measured using UTE and inversion recovery UTE (IR-UTE) imaging techniques. Macromolecular proton density (MMPD), a collagen representation, was measured using TWPD and macromolecular fraction (MMF) obtained from two-pool UTE magnetization transfer (UTE-MT) modeling. The correlations between proton densities and μCT-based measures were investigated. The 3D-UTE-Cones techniques were further applied on ten young healthy (34 ± 3 years old) and five old (78 ± 6 years old) female volunteers to evaluate the techniques' feasibility for translational clinical applications. In the ex vivo study, PWPD showed the highest correlations with bone porosity and bone mineral density (BMD) (R = 0.79 and - 0.70, p