Identifying characteristics and clinical conditions associated with hand grip strength in adults: the Project Baseline Health Study.

Low hand grip strength (HGS) is associated with several conditions, but its value outside of the older adult population is unclear. We sought to identify the most salient factors associated with HGS from an extensive list of candidate variables while stratifying by age and sex. We used data from the initial visit from the Project Baseline Health Study (N = 2502) which captured detailed demographic, occupational, social, lifestyle, and clinical data. We applied MI-LASSO using group methods to determine variables most associated with HGS out of 175 candidate variables. We performed analyses separately for sex and age (< 65 vs. ≥ 65 years). Race was associated with HGS to varying degrees across groups. Osteoporosis and osteopenia were negatively associated with HGS in female study participants. Immune cell counts were negatively associated with HGS for male participants ≥ 65 (neutrophils) and female participants (≥ 65, monocytes; < 65, lymphocytes). Most findings were age and/or sex group-specific; few were common across all groups. Several of the variables associated with HGS in each group were novel, while others corroborate previous research. Our results support HGS as a useful indicator of a variety of clinical characteristics; however, its utility varies by age and sex.

The impact of prenatal alcohol, synthetic cannabinoid and co-exposure on behavioral adaptations in adolescent offspring and alcohol self-administration in adulthood.

Prenatal exposure to alcohol or cannabinoids can produce enduring neurobiological, cognitive, and behavioral changes in the offspring. Furthermore, prenatal co-exposure to alcohol and cannabinoids induces malformations in brain regions associated with reward and stress-related circuitry. This study examined the effects of co-exposure to alcohol and the synthetic cannabinoid (SCB) CP55,940 throughout gastrulation and neurulation in rats on basal corticosterone levels and a battery of behavioral tests during adolescence and alcohol self-administration in adulthood. Importantly, we find that prenatal alcohol exposure (PAE) caused lower baseline corticosterone levels in adolescent males and females. Co-exposure to alcohol + CP produced hyperactivity during open field test in males, but not females. During the two-bottle choice alcohol-drinking procedure, prenatal cannabinoid exposed male and female adolescent rats drank more alcohol than their vehicle-exposed controls. In adulthood, female rats treated with prenatal cannabinoid exposure (PCE), showed an overall total increase in alcohol intake during alcohol self-administration; but this was not found in males. When the reinforcer was changed to a 1% sucrose solution, male rats exposed to PCE, showed a reduced self-administration compared to vehicle-exposed males, potentially indicative of an anhedonic response. This lower self-administration persisted when 20% alcohol was reintroduced to the sucrose solution. Lastly, following an abstinence period, there were no changes due to prenatal drug exposure in either males or females. Overall, these data suggest lasting consequences of prenatal alcohol and cannabinoid exposure during adolescence and adulthood in male and female rats.

The impact of prenatal alcohol and synthetic cannabinoid exposure on behavioral adaptations in adolescent offspring and alcohol self-administration in adulthood.

Prenatal exposure to alcohol or cannabinoids can produce enduring neurobiological, cognitive, and behavioral changes in the offspring. Furthermore, prenatal co-exposure to alcohol and cannabinoids induces malformations in brain regions associated with reward and stress-related circuitry. This study examined the effects of co-exposure to alcohol and the synthetic cannabinoid (SCB) CP55,940 throughout gastrulation and neurulation in rats on basal corticosterone levels and a battery of behavioral tests during adolescence and alcohol self-administration in adulthood. Importantly, we find that prenatal alcohol exposure (PAE) caused lower baseline corticosterone levels in adolescent males and females. Co-exposure to alcohol + CP produced hyperactivity during open field test in males, but not females. During the two-bottle choice alcohol-drinking procedure, prenatal cannabinoid exposed male and female adolescent rats drank more alcohol than their vehicle-exposed controls. In adulthood, female rats treated with prenatal cannabinoid exposure (PCE), showed an overall total increase in alcohol intake during alcohol self-administration; but this was not found in males. When the reinforcer was changed to a 1% sucrose solution, male rats exposed to PCE, showed a reduced self-administration compared to vehicle-exposed males, potentially indicative of an anhedonic response. This lower self-administration persisted when 20% alcohol was reintroduced to the sucrose solution. Lastly, following an abstinence period, there were no changes due to prenatal drug exposure in either males or females. Overall, these data suggest lasting consequences of prenatal alcohol and cannabinoid exposure during adolescence and adulthood in male and female rats.

Developing evidence for building sanitation justice: A multi methods approach to understanding public restroom quantity, quality, accessibility, and user experiences.

Access to basic sanitation is a human right and a critical environmental determinant of health. In this paper, we detail the development of three tools to investigate sanitation justice: (1) our public restroom spatial database, (2) our field assessment tool, and (3) survey of restroom access experiences. We document our process to collect these data in a consistent, health equity-driven framework. Together, these tools comprise a suite of methods for the examination of public restrooms from the macro- to the micro-level, and highlight key opportunities to promote health and well-being among restroom-reliant populations (e.g., people experiencing homelessness) by advancing sanitation justice in the built environment. With an illustrative case study, we demonstrate how methods triangulation, using the tools in concert, can provide a comprehensive assessment of basic sanitation access in a given region-San Diego, CA. We also detail how each tool can also be used separately to assess key sanitation justice and health equity questions that may be of interest to researchers, public health practitioners, policymakers, and advocates, including: (1) where do public restrooms exist (mapping)?; (2) how accessible are public restroom facilities, and what health-supportive features do they have (field assessment)?; and (3) what are the experiences of people most reliant on the available public restroom facilities (survey)? The results of our case study demonstrate that these adaptable tools can be used to provide meaningful data on and a holistic picture of public restroom quantity, quality, accessibility, and the experiences of public restroom users in a given region.

Blood Pressure Classification Status in Children With CKD Following Adoption of the 2017 American Academy of Pediatrics Guideline.

RATIONALE & OBJECTIVE: Accurate detection of hypertension is crucial for clinical management of pediatric chronic kidney disease (CKD). The 2017 American Academy of Pediatrics (AAP) clinical practice guideline for childhood hypertension included new normative blood pressure (BP) values and revised definitions of BP categories. In this study, we examined the effect of applying the AAP guideline's normative data and definitions to the Chronic Kidney Disease in Children (CKiD) cohort compared with use of normative data and definitions from the 2004 Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Children and adolescents in the CKiD cohort. EXPOSURE: Clinic BP measurements. OUTCOME: BP percentiles and hypertension stages calculated using the 2017 AAP guideline and the Fourth Report from 2004. ANALYTICAL APPROACH: Agreement analysis compared the estimated percentile and prevalence of high BP based on the 2017 guideline and 2004 report to clinic and combined ambulatory BP readings. RESULTS: The proportion of children classified as having normal clinic BP was similar using the 2017 and 2004 systems, but the use of the 2017 normative data classified more participants as having stages 1-2 hypertension (22% vs 11%), with marginal reproducibility (κ=0.569 [95% CI, 0.538-0.599]). Those identified as having stage 2 hypertension by the 2017 guideline had higher levels of proteinuria compared with those identified using the 2004 report. Comparing use of the 2017 guideline and the 2004 report in terms of ambulatory BP monitoring categories, there were substantially more participants with white coat (3.5% vs 1.5%) and ambulatory (15.5% vs 7.9%) hypertension, but the proportion with masked hypertension was lower (40.2% vs 47.8%, respectively), and the percentage of participants who were normotensive was similar (40.9% vs 42.9%, respectively). Overall, there was good reproducibility (κ=0.799 [95% CI, 0.778-0.819]) of classification by ambulatory BP monitoring. LIMITATIONS: Relationship with long-term progression and target organ damage was not assessed. CONCLUSIONS: A greater percentage of children with CKD were identified as having hypertension based on both clinic and ambulatory BP when using the 2017 AAP guideline versus the Fourth Report from 2004, and the 2017 guideline better discriminated those with higher levels of proteinuria. The substantial differences in the classification of hypertension when using the 2017 guideline should inform clinical care.

Extracorporeal Membrane Oxygenation Outcomes in Children With Preexisting Neurologic Disorders or Neurofunctional Disability.

OBJECTIVE: Patient selection for pediatric extracorporeal membrane oxygenation (ECMO) support has broadened over the years to include children with pre-existing neurologic morbidities. We aimed to determine the prevalence and nature of pre-ECMO neurologic disorders or disability and investigate the association between pre-ECMO neurologic disorders or disability and mortality and unfavorable neurologic outcome. DESIGN: Multicenter retrospective observational cohort study. SETTING: Eight hospitals reporting to the Pediatric ECMO Outcomes Registry between October 2011 and June 2019. PATIENTS: Children younger than 18 years supported with venoarterial or venovenous ECMO. INTERVENTIONS: The primary exposure was presence of pre-ECMO neurologic disorders or moderate-to-severe disability, defined as Pediatric Cerebral Performance Category (PCPC) or Pediatric Overall Performance Category (POPC) 3-5. The primary outcome was unfavorable outcome at hospital discharge, defined as in-hospital mortality or survival with moderate-to-severe disability (discharge PCPC 3-5 with deterioration from baseline). MEASUREMENTS AND MAIN RESULTS: Of 598 children included in the final cohort, 68 of 598 (11%) had a pre-ECMO neurologic disorder, 70 of 595 (12%) had a baseline PCPC 3-5, and 189 of 592 (32%) had a baseline POPC 3-5. The primary outcome of in-hospital mortality ( n = 267) or survival with PCPC 3-5 with deterioration from baseline ( n = 39) was observed in 306 of 598 (51%). Overall, one or more pre-ECMO neurologic disorders or disability were present in 226 of 598 children (38%) but, after adjustment for age, sex, diagnostic category, pre-ECMO cardiac arrest, and ECMO mode, were not independently associated with increased odds of unfavorable outcome (unadjusted odds ratio [OR], 1.34; 95% CI, 1.07-1.69; multivariable adjusted OR, 1.30; 95% CI, 0.92-1.82). CONCLUSIONS: In this exploratory study using a multicenter pediatric ECMO registry, more than one third of children requiring ECMO support had pre-ECMO neurologic disorders or disability. However, pre-existing morbidities were not independently associated with mortality or unfavorable neurologic outcomes at hospital discharge after adjustment for diagnostic category and other covariates.

General Anxiety Disorder-7 Questionnaire as a marker of low socioeconomic status and inequity.

BACKGROUND: The General Anxiety Disorder-7 (GAD-7) questionnaire is a standard tool used for screening and follow-up of patients with Generalized Anxiety Disorder (GAD). Although it is generally accepted that anxiety correlates with clinical and psychosocial stressors, precise quantitative data is limited on the relations among GAD-7, traditional biomarkers, and other measures of health. Further research is needed about how GAD-7 relates to race, ethnicity, and socioeconomic status (SES) as an assembly. We determined how multiple demographic and socioeconomic data correlate with the participants' GAD-7 results when compared with laboratory, physical function, clinical, and other biological markers. METHODS: The Project Baseline Health Study (BHS) is a prospective cohort of adults representing several populations in the USA. We analyzed a deeply phenotyped group of 2502 participants from that study. Measures of interest included: clinical markers or history of medical diagnoses; physical function markers including gait, grip strength, balance time, daily steps, and echocardiographic parameters; psychometric measurements; activities of daily living; socioeconomic characteristics; and laboratory results. RESULTS: Higher GAD-7 scores were associated with female sex, younger age, and Hispanic ethnicity. Measures of low SES were also associated with higher scores, including unemployment, income ≤$25,000, and ≤12 years of education. After adjustment for 158 demographic, clinical, laboratory, and symptom characteristics, unemployment and overall higher SES risk scores were highly correlated with anxiety scores. Protective factors included Black race and older age. LIMITATIONS: Correlations identified in this cross-sectional study cannot be used to infer causal relationships; further, we were not able to account for possible use of anxiety treatments by study participants. CONCLUSIONS: These findings highlight the importance of understanding anxiety as a biopsychosocial entity. Clinicians and provider organizations need to consider both the physical manifestations of the disorder and their patients' social determinants of health when considering treatment pathways and designing interventions.

Longitudinal Associations between Low Serum Bicarbonate and Linear Growth in Children with CKD.

Background: Poor linear growth is a consequence of chronic kidney disease (CKD) that has been linked to adverse outcomes. Metabolic acidosis (MA) has been identified as a risk factor for growth failure. We investigated the longitudinal relationship between MA and linear growth in children with CKD and examined whether treatment of MA modified linear growth. Methods: To describe longitudinal associations between MA and linear growth, we used serum bicarbonate levels, height measurements, and standard deviation (z scores) of children enrolled in the prospective cohort study Chronic Kidney Disease in Children. Analyses were adjusted for covariates recognized as correlating with poor growth, including demographic characteristics, glomerular filtration rate (GFR), proteinuria, calcium, phosphate, parathyroid hormone, and CKD duration. CKD diagnoses were analyzed by disease categories, nonglomerular or glomerular. Results: The study population included 1082 children with CKD: 808 with nonglomerular etiologies and 274 with glomerular etiologies. Baseline serum bicarbonate levels ≤22 mEq/L were associated with worse height z scores in all children. Longitudinally, serum bicarbonate levels ≤18 and 19-22 mEq/L were associated with worse height z scores in children with nonglomerular CKD causes, with adjusted mean values of -0.39 (95% CI, -0.58 to -0.2) and -0.17 (95% CI, -0.28 to -0.05), respectively. Children with nonglomerular disease and more severe GFR impairment had a higher risk for worse height z score. A significant association was not found in children with glomerular diseases. We also investigated the potential effect of treatment of MA on height in children with a history of alkali therapy use, finding that only persistent users had a significant positive association between their height z score and higher serum bicarbonate levels. Conclusions: We observed a longitudinal association between MA and lower height z score. Additionally, persistent alkali therapy use was associated with better height z scores. Future clinical trials of alkali therapy need to evaluate this relationship prospectively.

Pediatric ECMO: unfavorable outcomes are associated with inflammation and endothelial activation.

BACKGROUND: Inflammatory and endothelial activation responses during extracorporeal membrane oxygenation (ECMO) support in children are poorly understood. In this study, we aimed to determine if circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and with neurologic outcomes in children on ECMO. METHODS: We conducted a secondary analysis of a two-center prospective observational study of 99 neonatal and pediatric ECMO patients. Inflammatory (interferon gamma [IFNγ], interleukin-6 [IL-6], IL-1ß, tumor necrosis factor alpha [TNFα]), endothelial activation (E-selectin, P-selectin, intercellular adhesion molecule-3 [ICAM-3], thrombomodulin [TM]), and fibrinolytic markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1]) were measured in plasma on days 1, 2, 3, 5, 7, and every third day thereafter during the ECMO course. RESULTS: All ECMO day 1 inflammatory biomarkers were significantly elevated in children with abnormal vs. normal neuroimaging. ECMO day 1 and peak levels of IL-6 and PAI-1 were significantly elevated in children who died compared to those who survived to hospital discharge. Tested biomarkers showed no significant association with long-term neurobehavioral outcomes measured using the Vineland Adaptive Behavioral Scales, Second Edition. CONCLUSIONS: High levels of circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and abnormal neuroimaging in children on ECMO. IMPACT: The inflammatory, endothelial activation, and fibrinolytic profile of children on ECMO differs by primary indication for extracorporeal support. Proinflammatory biomarkers on ECMO day 1 are associated with abnormal neurologic imaging in children on ECMO in univariable but not multivariable models. In multivariable models, a pronounced proinflammatory and prothrombotic biomarker profile on ECMO day 1 and longitudinally was significantly associated with mortality. Further studies are needed to identify inflammatory, endothelial, and fibrinolytic profiles associated with increased risk for neurologic injury and mortality through potential mediation of bleeding and thrombosis.

Cyclohexanone Exposure in Children on Extracorporeal Membrane Oxygenation Support.

The aim of this study was to determine if plasma cyclohexanone and metabolites are associated with clinical outcomes of children on extracorporeal membrane oxygenation (ECMO) support. We performed a secondary analysis of a prospective observational study of children on ECMO support at two academic centers between July 2010 and June 2015. We measured plasma cyclohexanone and metabolites on the first and last days of ECMO support. Unfavorable outcome was defined as in-hospital death or discharge Pediatric Cerebral Performance Category score > 2 or decline ≥ 1 from baseline. Among 90 children included, 49 (54%) had unfavorable outcome at discharge. Cyclohexanediol, a cyclohexanone metabolite, was detected in all samples and at both time points; concentrations on the first ECMO day were significantly higher in those with unfavorable versus favorable outcome at hospital discharge (median, 5.7 ng/µl; interquartile range [IQR], 3.3-10.6 ng/µl vs. median, 4.2 ng/µl; IQR, 1.7-7.3 ng/µl; p = 0.04). Twofold higher cyclohexanediol concentrations on the first ECMO day were associated with increased risk of unfavorable outcome at hospital discharge (multivariable-adjusted hazard ratio [HR], 1.24 [95% CI, 1.05-1.48]). Higher cyclohexanediol concentrations on the first ECMO day were not significantly associated with new abnormal neuroimaging or 1-year Vineland Adaptive Behavior Scales-II score < 85 or death among survivors.

Patterns of recombinant growth hormone therapy use and growth responses among children with chronic kidney disease.

BACKGROUND: Recombinant growth hormone (rGH) is an efficacious therapy for growth failure in children with chronic kidney disease (CKD). We described rGH use and estimated its relationship with growth and kidney function in the Chronic Kidney Disease in Children (CKiD) cohort. METHODS: Participants included those with growth failure, prevalent rGH users, and rGH initiators who did not meet growth failure criteria. Among those with growth failure, height z scores and GFR were compared between rGH initiators and non-initiators across 42 months. Inverse probability weights accounted for differences in baseline variables in weighted linear regressions. RESULTS: Among 148 children with growth failure and no previous rGH therapy, 42 (28%) initiated rGH therapy. Of the initiators, average age was 8.9 years, height z score was 2.50 standard deviations (SDs) (0.6th percentile), and GFR was 44 ml/min/1.73m2. They were compared to 106 children with growth failure who never initiated therapy (8.8 years, -2.33 SDs, and 51 ml/min/1.73m2). At 30 and 42 months after rGH, height increased +0.26 (95%CI: -0.11, +0.62) and +0.35 (95%CI: -0.17, +0.87) SDs, respectively, relative to those who did not initiate rGH. rGH was not associated with GFR. CONCLUSIONS: Participants with growth failure receiving rGH experienced significant growth, although this was attenuated relative to RCTs, and were more likely to have higher household income and lower GFR. A substantial number of participants, predominantly boys, without diagnosed growth failure received rGH and had the highest achieved height relative to mid-parental height. Since rGH was not associated with accelerated GFR decline, increasing rGH use in this population is warranted.

L-type calcium channel blocker use and proteinuria among children with chronic kidney diseases.

BACKGROUND: Hypertension is common among children with chronic kidney disease (CKD), and dihydropyridine calcium channel blockers (dhCCBs) are frequently used as treatment. The impact of dhCCBs on proteinuria in children with CKD is unclear. METHODS: Data from 722 participants in the Chronic Kidney Disease in Children (CKiD) longitudinal cohort with a median age of 12 years were used to assess the association between dhCCBs and log transformed urine protein/creatinine levels as well as blood pressure control measured at annual visits. Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) use was evaluated as an effect measure modifier. RESULTS: Individuals using dhCCBs had 18.8% higher urine protein/creatinine levels compared to those with no history of dhCCB or ACEi and ARB use. Among individuals using ACEi and ARB therapy concomitantly, dhCCB use was not associated with an increase in proteinuria. Those using dhCCBs had higher systolic and diastolic blood pressures. CONCLUSIONS: Use of dhCCBs in children with CKD and hypertension is associated with higher levels of proteinuria and was not found to be associated with improved blood pressure control.

Genital Hiatus Size and the Development of Prolapse Among Parous Women.

OBJECTIVE: In cross-sectional studies, pelvic organ prolapse is strongly associated with genital hiatus (GH) size. The objective of this study was to estimate prolapse incidence by the size of the GH among parous women followed prospectively. METHODS: Data were derived from a longitudinal study of pelvic floor disorders. Participants were followed annually for 2-9 years. Genital hiatus size and prolapse beyond the hymen were assessed with annual pelvic organ prolapse quantification examinations. Kaplan-Meier methods described prolapse-free survival as a function of GH size. Accounting for changes over time in GH size, lognormal models were used to estimate prolapse-free survival by GH size. This analysis was repeated separately for women who gave birth exclusively by cesarean versus those with at least one vaginal birth. RESULTS: Among 1,492 participants, median age at enrollment was 38 years; 153 (10.3%) developed prolapse over 2-9 years. The cumulative probability of prolapse increased substantially as the size of the GH increased. Lognormal models predicted that the estimated median time to develop prolapse would be 33.4 years for women with a persistent GH of 3 cm; in contrast, the estimated median time to develop prolapse would be 5.8 years for a GH of 4.5 cm or greater. Considering separately women who gave birth by cesarean versus those with at least 1 vaginal birth, GH size drastically modified prolapse risk in both birth groups. CONCLUSIONS: Prolapse incidence is strongly associated with GH size, regardless of delivery mode. These findings suggest that a wider GH is an important predictor of future prolapse risk.

Achieved clinic blood pressure level and chronic kidney disease progression in children: a report from the Chronic Kidney Disease in Children cohort.

BACKGROUND: Control of hypertension delays progression of pediatric chronic kidney disease (CKD), yet few data are available regarding what clinic blood pressure (BP) levels may slow progression. METHODS: Longitudinal BP data from children in the Chronic Kidney Disease in Children cohort study who had hypertension or an auscultatory BP ≥ 90th percentile were studied. BP categories were defined as the maximum systolic or diastolic BP percentile (< 50th, 50th to 75th, 75th to 90th, and ≥ 90th percentile) with time-updated classifications corresponding to annual study visits. The primary outcome was time to kidney replacement therapy or a 30% decline in estimated glomerular filtration rate. Cox proportional hazard models described the effect of each BP category compared to BP ≥ 90th percentile. RESULTS: Seven hundred fifty-four participants (median age 9.9 years at study entry) met inclusion criteria; 65% were male and 26% had glomerular CKD. Any BP < 90th percentile was associated with a decreased risk of progression for those with glomerular CKD (hazard ratio (HR), 0.63; 95% CI, 0.28-1.39 (< 50th); HR, 0.59; 95% CI, 0.28-1.26 (50th-75th); HR, 0.40; 95% CI, 0.18-0.93 (75th-90th)). Similar results were found for those with non-glomerular CKD: any BP < 90th percentile was associated with decreased risk of progression (HR, 0.78; 90% CI, 0.49-1.25 (< 50th); HR, 0.53; 95% CI, 0.33-0.84 (50th-75th); HR, 0.71; 95% CI, 0.46-1.08 (75th-90th)). CONCLUSIONS: Achieved clinic BP < 90th percentile was associated with slower CKD progression in children with glomerular or non-glomerular CKD. These data provide guidance for management of children with CKD in the office setting. Graphical abstract.

Outcomes of pediatric patients with oncologic disease or following hematopoietic stem cell transplant supported on extracorporeal membrane oxygenation: The PEDECOR experience.

BACKGROUND: Outcomes for patients with oncologic disease and/or after hematopoietic stem cell transplant (HSCT) requiring intensive care unit admission have improved, but indications for and outcomes after extracorporeal membrane oxygenation (ECMO) support in this population are poorly characterized. PROCEDURE: We analyzed data from consecutive patients < 18 years with oncologic disease and/or after HSCT reported to a pediatric ECMO registry by nine pediatric centers in the United States between 2011 and 2018. RESULTS: We identified 18 ECMO patients with oncologic disease and/or HSCT, and 415 ECMO controls matched with a propensity score algorithm based on age, gender, race, severity of illness at admission, and reason for ECMO. The primary indication for ECMO was respiratory failure in 66.7% in the oncologic disease and/or HSCT group, and in 70.7% in the matched ECMO control group. Eleven of 18 patients survived to hospital discharge (61.1%), similar to the matched control group (60.8%), P = 0.979. Children with oncologic disease and/or HSCT had lower mean platelet counts during ECMO and received higher volumes of platelets compared with the control group, mean 14.6 mL/kg/day (standard deviations [SD], 9.8) versus mean 9.3 mL/kg/day (SD, 10.4), P = 0.001. Of the 11 surviving children with oncologic disease and/or HSCT, five sustained new neurologic disorders (45.5%) versus 45 of 222 (20.3%) in the control group, P = 0.061. Bleeding complications were similar in the two groups. CONCLUSIONS: Outcomes of patients with oncologic disease and/or HSCT supported on ECMO in the current era are not significantly different compared with matched ECMO controls and are improved from previously published reports.

Quality and Publication of Emergency Medicine Trials Registered in ClinicalTrials.gov

INTRODUCTION: Promoting emergency medicine (EM) clinical trials research remains a priority. To characterize the status of clinical EM research, this study assessed trial quality, funding source, and publication of EM clinical trials and compared EM and non-EM trials on these key metrics. We also examined the volume of EM trials and their subspecialty areas. METHODS: We abstracted data from ClinicalTrials.gov (February 2000 - September 2013) and used individual study National Clinical Trial numbers to identify published trials (January 2007 - September 2016). We used descriptive statistics and chi-square tests to examine study characteristics by EM and non-EM status, and Kaplan-Meier curves and log-rank tests to compare time to publication of completed EM and non-EM studies. RESULTS: We found 638 interventional EM trials and 59,512 non-EM interventional trials conducted in the United States between February 2000 and September 2013, registered on ClinicalTrials.gov. EM studies were significantly less likely than non-EM studies to be National Institutes of Health-funded or to evaluate a drug or biologic. However, EM studies had significantly larger sample sizes, and were significantly more likely to use randomization and blinding. Overall, 34.3% of EM and 26.0% of non-EM studies were published in peer-reviewed journals. By subspecialty, more EM trials concerned medical/surgical and psychiatric/neurological conditions than trauma. CONCLUSION: Although EM studies were less likely to have received federal or industry funding, and the EM portfolio consisted of only 638 trials over the 14-year study period, the quality of EM trials surpassed that of non-EM trials, based on indices such as randomization and blinding. This novel finding bodes well for the future of clinical EM research, as does the higher proportion of published EM than non-EM trials. Our study also revealed that trauma studies were under-represented among EM studies. Periodic assessment of EM trials with the metrics used here could provide an informative and valuable longitudinal view of progress in clinical EM research.

Pelvic floor muscle strength and the incidence of pelvic floor disorders after vaginal and cesarean delivery.

BACKGROUND: Pelvic floor disorders (including urinary and anal incontinence and pelvic organ prolapse) are associated with childbirth. Injury to the pelvic floor muscles during vaginal childbirth, such as avulsion of the levator ani muscle, is associated with weaker pelvic floor muscle strength. As weak pelvic floor muscle strength may be a modifiable risk factor for the later development of pelvic floor disorders, it is important to understand how pelvic floor muscle strength affects the course of pelvic floor disorders over time. OBJECTIVE: To investigate the association between pelvic floor muscle strength and the incidence of pelvic floor disorders, and to identify maternal and obstetrical characteristics that modify the association. MATERIALS AND METHODS: This is a longitudinal study investigating pelvic floor disorders after childbirth. Participants were recruited 5-10 years after their first delivery and were assessed for pelvic floor disorders annually for up to 9 years. Stress incontinence, overactive bladder, and anal incontinence were assessed at each annual visit using the Epidemiology of Prolapse and Incontinence Questionnaire. Pelvic organ prolapse was assessed on physical examination, and was defined as descent of the vaginal walls or cervix beyond the hymen during forceful Valsalva. The primary exposure of interest was pelvic floor muscle strength, defined as the peak pressure during a voluntary pelvic muscle contraction (measured with a perineometer). The relationship between pelvic floor muscle strength and the cumulative incidence (time to event) of each pelvic floor disorder was evaluated using lognormal models, stratified by vaginal vs cesarean delivery. The relative hazard for each pelvic floor disorder (among those women free of the disorder at enrollment and thus more than 5-10 years from first delivery), was estimated using semiparametric proportional hazard models as a function of delivery mode, pelvic floor muscle strength, and other covariates. RESULTS: Of 1143 participants, the median age was 40 (interquartile range, 36.6-43.7) years, and 73% were multiparous. On perineometry, women with at least 1 vaginal delivery were more likely to have a low peak pressure, defined as <20 cm H2O (243 of 588 women with at least 1 vaginal delivery vs 107 of 555 women who delivered all of their children by cesarean delivery, P < .001). Among women who had at least 1 vaginal delivery, a pelvic floor muscle strength of <20 cm H2O was associated with a shorter time to event for stress incontinence (time ratio, 0.67; 95% confidence interval, 0.50-0.90), overactive bladder (time ratio, 0.67; 95% confidence interval, 0.51-0.86), and pelvic organ prolapse (time ratio, 0.76; 95% confidence interval, 0.65-0.88). No such association was found among women who delivered all of their children by cesarean delivery. Among women with at least 1 vaginal delivery and considering only pelvic floor disorders that developed during study observation (5-10 years after the first delivery), and controlling for maternal characteristics (body mass index and genital hiatus), women who had a peak pressure of <20 cm H2O had hazard ratios (relative to ≥20 cm H2O) of 1.16 (95% confidence interval, 0.74-1.81) for stress incontinence, 1.27 (95% confidence interval, 0.78-2.05) for overactive bladder, and 1.43 (95% confidence interval, 0.99-2.07) for pelvic organ prolapse. Among women who delivered all of their children by cesarean delivery, there was no association between muscle strength and relative hazard of pelvic floor disorders when controlling for maternal characteristics. CONCLUSION: After vaginal delivery, but not cesarean delivery, the cumulative incidence of pelvic organ prolapse, stress incontinence, and overactive bladder is associated with pelvic muscle strength, but the associations attenuate when adjusting for genital hiatus and body mass index.

Longitudinal Changes in the Genital Hiatus Preceding the Development of Pelvic Organ Prolapse.

We aimed to explore relationships between changes in genital hiatus (GH) and development of pelvic organ prolapse using data from the Mothers' Outcomes After Delivery (MOAD) Study, a Baltimore, Maryland, cohort study of parous women who underwent annual assessments during 2008-2018. Prolapse was defined as any vaginal segment protrusion beyond the hymen or reported prolapse surgery. For each case, 5 controls (matched on birth type and interval from first delivery to study enrollment) were selected using incidence sampling methods. We used a mixed model whose fixed effects described the initial size and slope of the GH as a function of prolapse status (case vs. control) and with nested (women within matched sets) random effects. Among 1,198 women followed for 1.0-7.3 years, 153 (13%) developed prolapse; 754 controls were matched to those women, yielding 3,664 visits for analysis. GH was 20% larger among the cases at enrollment (3.16 cm in cases vs. 2.62 cm in controls; P < 0.001), and the mean rate of increase in the size of the GH was more than 3 times greater (0.56 cm per 5-year period vs. 0.15 cm per 5-year period in controls; P < 0.001). Thus, to identify women at highest risk for developing prolapse, health-care providers could evaluate not simply the size of the GH but also changes in the GH over time.

Association of Delivery Mode With Pelvic Floor Disorders After Childbirth.

Importance: Pelvic floor disorders (eg, urinary incontinence), which affect approximately 25% of women in the United States, are associated with childbirth. However, little is known about the course and progression of pelvic floor disorders over time. Objective: To describe the incidence of pelvic floor disorders after childbirth and identify maternal and obstetrical characteristics associated with patterns of incidence 1 to 2 decades after delivery. Design, Setting, and Participants: Women were recruited from a community hospital for this cohort study 5 to 10 years after their first delivery and followed up annually for up to 9 years. Recruitment was based on mode of delivery; delivery groups were matched for age and years since first delivery. Of 4072 eligible women, 1528 enrolled between October 2008 and December 2013. Annual follow-up continued through April 2017. Exposures: Participants were categorized into the following mode of delivery groups: cesarean birth (cesarean deliveries only), spontaneous vaginal birth (≥1 spontaneous vaginal delivery and no operative vaginal deliveries), or operative vaginal birth (≥1 operative vaginal delivery). Main Outcomes and Measures: Stress urinary incontinence (SUI), overactive bladder (OAB), and anal incontinence (AI), defined using validated threshold scores from the Epidemiology of Prolapse and Incontinence Questionnaire, and pelvic organ prolapse (POP), measured using the Pelvic Organ Prolapse Quantification Examination. Cumulative incidences, by delivery group, were estimated using parametric methods. Hazard ratios, by exposure, were estimated using semiparametric models. Results: Among 1528 women (778 in the cesarean birth group, 565 in the spontaneous vaginal birth group, and 185 in the operative vaginal birth group), the median age at first delivery was 30.6 years, 1092 women (72%) were multiparous at enrollment (2887 total deliveries), and the median age at enrollment was 38.3 years. During a median follow-up of 5.1 years (7804 person-visits), there were 138 cases of SUI, 117 cases of OAB, 168 cases of AI, and 153 cases of POP. For spontaneous vaginal delivery (reference), the 15-year cumulative incidences of pelvic floor disorders after first delivery were as follows: SUI, 34.3% (95% CI, 29.9%-38.6%); OAB, 21.8% (95% CI, 17.8%-25.7%); AI, 30.6% (95% CI, 26.4%-34.9%), and POP, 30.0% (95% CI, 25.1%-34.9%). Compared with spontaneous vaginal delivery, cesarean delivery was associated with significantly lower hazard of SUI (adjusted hazard ratio [aHR], 0.46 [95% CI, 0.32-0.67]), OAB (aHR, 0.51 [95% CI, 0.34-0.76]), and POP (aHR, 0.28 [95% CI, 0.19-0.42]), while operative vaginal delivery was associated with significantly higher hazard of AI (aHR, 1.75 [95% CI, 1.14-2.68]) and POP (aHR, 1.88 [95% CI, 1.28-2.78]). Stratifying by delivery mode, the hazard ratios for POP, relative to a genital hiatus size less than or equal to 2.5 cm, were 3.0 (95% CI, 1.7-5.3) for a genital hiatus size of 3 cm and 9.0 (95% CI, 5.5-14.8) for a genital hiatus size greater than or equal to 3.5 cm. Conclusions and Relevance: Compared with spontaneous vaginal delivery, cesarean delivery was associated with significantly lower hazard for stress urinary incontinence, overactive bladder, and pelvic organ prolapse, while operative vaginal delivery was associated with significantly higher hazard of anal incontinence and pelvic organ prolapse. A larger genital hiatus was associated with increased risk of pelvic organ prolapse independent of delivery mode.

Evaluating concurrent validity of criminal justice and clinical assessments among women on probation.

BACKGROUND: Women in the criminal justice (CJ) system experience complex and comorbid medical, psychiatric, and substance use disorders, which often contribute to CJ involvement. To identify intersections between CJ and health needs, we calculated Spearman r correlations between concurrent CJ and clinical assessments from women on probation in Connecticut who were enrolled in a clinical trial. We examined longitudinal trends in CJ risk scores over 9 years of observation (2005-2014), modeling time to probation recidivism with shared gamma frailty models and comparing contiguous time points by Wilcoxon matched-pairs signed rank tests. RESULTS: Women (N = 31) were predominantly white (67.7%) with at least some high school education (58.1%) and mostly unemployed (77.4%) and unstably housed (83.9%). Most met clinical criteria for severe substance use and/or psychiatric disorders. Concurrent measures of substance use, mental health, social support, partnerships, and risk by the Level of Service Inventory-Revised (LSI-R) and clinical assessments were not significantly correlated. The LSI-R personal/emotional sub-score, however, positively correlated with the Addiction Severity Index psychiatric composite score (r = 0.40, 95% CI 0.03-0.68, p = 0.03). After adjusting for age, race and number of previous events, having some high school education versus none marginally decreased the hazard for probation recidivism and having > 5 inpatient psychiatric admissions versus none increased the hazard of probation recidivism 7-fold (HR 7.49, 95% CI 1.33-42.12, p = 0.022). Women with 0-1 recurrent probation terms (n = 16) had a significantly lower mean LSI-R score than those with 2-4 recurrent probation terms (35.9 [SD 6.4] versus 39.2 [SD 3.0], p = 0.019), but repeated LSI-R scores did not change over time, nor vary significantly beyond the group mean. CONCLUSIONS: In this small, quantitative study of women on probation, widely used CJ assessment tools poorly reflected women's comorbid medical, psychiatric, and substance use needs and varied minimally over time. Findings illustrate the limitations of contemporary CJ assessment tools for women with complex needs. The field requires more comprehensive assessments of women's social and health needs to develop individualized targeted case plans that simultaneously improve health and CJ outcomes.