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The Affordable Care Act has been associated with increased Medicaid coverage for childbirth among low-income US women. We hypothesized that Medicaid expansion was associated with increased use of labor neuraxial analgesia.We performed a cross-sectional analysis of US women with singleton live births who underwent vaginal delivery or intrapartum cesarean delivery between 2009 and 2017. Data were sourced from births in 26 US states that used the 2003 Revised US Birth Certificate. Difference-in-difference linear probability models were used to compare changes in the prevalence of neuraxial labor analgesia in 15 expansion and 11 nonexpansion states before and after Medicaid expansion. Models were adjusted for potential maternal and obstetric confounders with standard errors clustered at the state level.The study sample included 5,703,371 births from 15 expansion states and 5,582,689 births from 11 nonexpansion states. In the preexpansion period, the overall rate of neuraxial analgesia in expansion and nonexpansion states was 73.2% vs 76.3%. Compared with the preexpansion period, the rate of neuraxial analgesia increased in the postexpansion period by 1.7% in expansion states (95% CI, 1.6-1.8) and 0.9% (95% CI, 0.9-1.0) in nonexpansion states. The adjusted difference-in-difference estimate comparing expansion and nonexpansion states was 0.47% points (95% CI, -0.63 to 1.57; P = .39).Medicaid expansion was not associated with an increase in the rate of neuraxial labor analgesia in expansion states compared to the change in nonexpansion states over the same time period. Increasing Medicaid eligibility alone may be insufficient to increase the rate of neuraxial labor analgesia.

Background Internal medicine residents face numerous career options after residency training. Little is known about when residents make their final career choice. Objective We assessed the timing and predictive factors of final career choices among internal medicine residents at graduation, including demographics, pre-residency career preferences, and rotation scheduling. Methods We conducted a retrospective study of graduates of an academic internal medicine residency program from 2014 to 2017. Main measures included demographics, rotation schedules, and self-reported career choices for residents at 5 time points: recruitment day, immediately after Match Day, end of postgraduate year 1 (PGY-1), end of PGY-2, and at graduation. Results Of the 138 residents eligible for the study, 5 were excluded based on participation in a fast-track program for an Accreditation Council for Graduate Medical Education subspecialty fellowship. Among the remaining 133 residents, 48 (36%) pursued general internal medicine fields and 78 (59%) pursued fellowship training. Career choices from recruitment day, Match Day, and PGY-1 were only weakly predictive of the career choice. Many choices demonstrated low concordance throughout training, and general medicine fields (primary care, hospital medicine) were frequently not decided until after PGY-2. Early clinical exposure to subspecialty rotations did not predict final career choice. Conclusions Early career choices before and during residency training may have low predictability toward final career choices upon graduation in internal medicine. These choices may continue to have low predictability beyond PGY-2 for many specialties. Early clinical exposure may not predict final career choice for subspecialties.

BACKGROUND: Little is known about how to effectively train residents with point-of-care ultrasonography (POCUS) despite increasing usage. OBJECTIVE: This study aimed to assess whether handheld ultrasound devices (HUDs), alongside a year-long lecture series, improved trainee image interpretation skills with POCUS. METHODS: Internal medicine intern physicians (N = 149) at a single academic institution from 2016 to 2018 participated in the study. The 2017 interns (n = 47) were randomized 1:1 to receive personal HUDs (n = 24) for patient care vs no-HUDs (n = 23). All 2017 interns received a repeated lecture series regarding cardiac, thoracic, and abdominal POCUS. Interns were assessed on their ability to interpret POCUS images of normal/abnormal findings. The primary outcome was the difference in end-of-the-year assessment scores between interns randomized to receive HUDs vs not. Secondary outcomes included trainee scores after repeating lectures and confidence with POCUS. Intern scores were also compared with historical (2016, N = 50) and contemporaneous (2018, N = 52) controls who received no lectures. RESULTS: Interns randomized to HUDs did not have significantly higher image interpretation scores (median HUD score: 0.84 vs no-HUD score: 0.84; P = .86). However, HUD interns felt more confident in their abilities. The 2017 cohort had higher scores (median 0.84), compared with the 2016 historical control (median 0.71; P = .001) and 2018 contemporaneous control (median 0.48; P < .001). Assessment scores improved after first-time exposure to the lecture series, while repeated lectures did not improve scores. CONCLUSIONS: Despite feeling more confident, personalized HUDs did not improve interns’ POCUS-related knowledge or interpretive ability. Repeated lecture exposure without further opportunities for deliberate practice may not be beneficial for mastering POCUS.

BACKGROUND Adherence to endocrine therapy for breast cancer is often inadequate, in part because of out-of-pocket costs for medication. Numerous states have enacted parity laws to limit patient cost-sharing for oral anticancer drugs. The objective of this study was to estimate the impact of these laws on patient copayments for and adherence to oral endocrine therapy for breast cancer. METHODS Administrative health insurance claims data from 2007 to 2014 derived from a US health care database were used to identify female patients aged 18 to 64 years with invasive cancer or ductal carcinoma in situ of the breast who initiated endocrine therapy and were enrolled in fully insured health plans in states that either enacted parity legislation between 2008 and 2013 or had not yet enacted such legislation by 2015. Differences-in-differences analysis was used to compare copayments for and adherence to endocrine therapy during the 1-year period before and after each year of legislation enactment. RESULTS In total, 6900 individuals who received 7778 unique drug therapy courses were identified. Parity legislation was associated with significant decreases in the 25th percentile of copayments for anastrozole of $4.39 (95% confidence interval [CI], -$4.52 to -$4.26; P < .001) and for exemestane of $3.08 (95% CI, -$4.80 to -$1.35; P < .001). The median copayment for exemestane decreased by $10.25 (95% CI, -$12.61 to -$7.89; P < .001). A higher median monthly copayment was significantly associated with a greater risk of medication nonadherence (adjusted risk ratio, 1.006 per dollar increase; P < .001). CONCLUSIONS Parity laws had a modest effect on lowering the cost of anastrozole and exemestane, but more focused efforts to limit out-of-pocket costs for endocrine therapy may have a greater impact on medication adherence.

OBJECTIVE To assess the relation between maternal body mass index (BMI) and pregnancy-related venous thromboembolism (VTE). DESIGN Cohort study. SETTING AND POPULATION A total of 2 449 133 women with singleton pregnancies who underwent delivery hospitalisation in California between 2008 and 2012. METHODS Association of pre-pregnancy BMI and the risk of an antepartum and postpartum VTE was examined using logistic regression, with normal BMI as reference. MAIN OUTCOME MEASURES Antepartum and postpartum VTE-related hospitalisation. RESULTS The prevalence of antepartum and postpartum VTE increased with increasing BMI (antepartum: 2.3, 3.0, 3.8, 4.2, 4.7, and 10.6 per 10 000 women for underweight, normal BMI, overweight, obesity class I, II, and III, respectively, P

Low birthweight (2500 g) is often used as a population-level indicator of maternal-child health, as it is easy to measure and correlates with poorer infant health outcomes. However, it conflates preterm birth and intrauterine growth restriction, which have different causal pathways and require different approaches to prevention. Small for gestational age (SGA) (a proxy for growth restriction) and preterm birth may be more informative measures. We evaluated low birthweight as a population-level indicator.We conducted a population-based cohort study of singleton live births in New South Wales (NSW), Australia, using linked data from 1994-2006 birth, hospital, death and educational records, with follow-up until 2014. Outcomes of babies born of low birthweight, preterm and SGA were compared with well-grown term infants (i.e. not low birthweight or SGA). Overlap between groups and temporal trends were also examined.Of 1 093 765 singleton live births, 47 946 (4.4%) infants were low birthweight and had poorer outcomes than well-grown term infants (2.7% vs. 0.1% infant mortality; 13% vs. 6% below national minimum numeracy standard). SGA and preterm infants also had poorer outcomes (0.5%, 2.3% infant mortality respectively; 10%, 11% below numeracy standard) but 80% of SGA and 47% of preterm infants were not low birthweight. For all outcomes, low birthweight identified a smaller proportion of infants with poor outcomes than preterm birth and than either SGA or low birthweight at term. The proportion of low-birthweight births remained constant over time, while the proportion of births that were preterm increased and proportion of SGA decreased.Low birthweight, SGA and preterm infants are all at higher risk of poorer outcomes but low birthweight inadequately captures, and masks trends in, both preterm births and births that are SGA. Reporting preterm births and an indicator of growth restriction at term will identify vulnerable groups better than using the measure of low birthweight.

Background Risk factors for postpartum hemorrhage, such as chorioamnionitis and multiple gestation, have been identified in previous epidemiologic studies. However, existing data describing the association between gestational age at delivery and postpartum hemorrhage are conflicting. The aim of this study was to assess the association between gestational age at delivery and postpartum hemorrhage. Methods The authors conducted a population-based retrospective cohort study of women who underwent live birth delivery in Sweden between 2014 and 2017 and in California between 2011 and 2015. The primary exposure was gestational age at delivery. The primary outcome was postpartum hemorrhage, classified using International Classification of Diseases, Ninth Revision—Clinical Modification codes for California births and a blood loss greater than 1,000 ml for Swedish births. The authors accounted for demographic and obstetric factors as potential confounders in the analyses. Results The incidences of postpartum hemorrhage in Sweden (23,323/328,729; 7.1%) and in California (66,583/2,079,637; 3.2%) were not comparable. In Sweden and California, the incidence of postpartum hemorrhage was highest for deliveries between 41 and 42 weeks’ gestation (7,186/75,539 [9.5%] and 8,921/160,267 [5.6%], respectively). Compared to deliveries between 37 and 38 weeks, deliveries between 41 and 42 weeks had the highest adjusted odds of postpartum hemorrhage (1.62 [95% CI, 1.56 to 1.69] in Sweden and 2.04 [95% CI, 1.98 to 2.09] in California). In both cohorts, the authors observed a nonlinear (J-shaped) association between gestational age and postpartum hemorrhage risk, with 39 weeks as the nadir. In the sensitivity analyses, similar findings were observed among cesarean deliveries only, when postpartum hemorrhage was classified only by International Classification of Diseases, Tenth Revision—Clinical Modification codes, and after excluding women with abnormal placentation disorders. Conclusions The postpartum hemorrhage incidence in Sweden and California was not comparable. When assessing a woman’s risk for postpartum hemorrhage, clinicians should be aware of the heightened odds in women who deliver between 41 and 42 weeks’ gestation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Self-help group (SHG) interventions have been widely studied in low and middle income countries. However, there is little data on specific impacts of health layering, or adding health education modules upon existing SHGs which were formed primarily for economic empowerment. We examined three SHG interventions from 2012-2017 in Bihar, India to test the hypothesis that health-layering of SHGs would lead to improved health-related behaviours of women in SHGs. Methods A model for health layering of SHGs – Parivartan – was developed by the non-governmental organisation (NGO), Project Concern International, in 64 blocks of eight districts. Layering included health modules, community events and review mechanisms. The health layering model was adapted for use with government-led SHGs, called JEEViKA+HL, in 37 other blocks of Bihar. Scale-up of government-led SHGs without health layering (JEEViKA) occurred contemporaneously in 433 other blocks, providing a natural comparison group. Using Community-based Household Surveys (CHS, rounds 6-9) by CARE India, 62 reproductive, maternal, newborn and child health and nutrition (RMNCHN) and sanitation indicators were examined for SHGs with health layering (Pavivartan SHGs and JEEViKA+HL SHGs) compared to those without. We calculated mean, standard deviation and odds ratios of indicators using surveymeans and survey logistic regression. Results In 2014, 64% of indicators were significantly higher in Parivartan members compared to non-members residing in the same blocks. During scale up, from 2015-17, half (50%) of indicators had significantly higher odds in health layered SHG members (Parivartan or JEEViKA+HL) in 101 blocks compared to SHG members without health layering (JEEViKA) in 433 blocks. Conclusions Health layering of SHGs was demonstrated by an NGO-led model (Parivartan), adapted and scaled up by a government model (JEEViKA+HL), and associated with significant improvements in health compared to non-health-layered SHGs (JEEViKA). These results strengthen the evidence base for further layering of health onto the SHG platform for scale-level health change. Study registration ClinicalTrials.gov number NCT02726230

Background The Government of Bihar (GoB) in India, the Bill and Melinda Gates Foundation and several non-governmental organisations launched the Ananya program aimed to support the GoB to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) statewide. Here we summarise changes in indicators attained during the initial two-year pilot phase (2012-2013) of implementation in eight focus districts of approximately 28 million population, aimed to inform subsequent scale-up. Methods The quasi-experimental impact evaluation included statewide household surveys at two time points during the pilot phase: January-April 2012 (“baseline”) including an initial cohort of beneficiaries and January-April 2014 (“midline”) with a new cohort. The two arms were: 1) eight intervention districts, and 2) a comparison arm comprised of the remaining 30 districts in Bihar where Ananya interventions were not implemented. We analysed changes in indicators across the RMNCHN continuum of care from baseline to midline in intervention and comparison districts using a difference-in-difference analysis. Results Indicators in the two arms were similar at baseline. Overall, 40% of indicators (20 of 51) changed significantly from baseline to midline in the comparison districts unrelated to Ananya; two-thirds (n = 13) of secular indicator changes were in a direction expected to promote health. Statistically significant impact attributable to the Ananya program was found for 10% (five of 51) of RMNCHN indicators. Positive impacts were most prominent for mother’s behaviours in contraceptive utilisation. Conclusions The Ananya program had limited impact in improving health-related outcomes during the first two-year period covered by this evaluation. The program’s theories of change and action were not powered to observe statistically significant differences in RMNCHN indicators within two years, but rather aimed to help inform program improvements and scale-up. Evaluation of large-scale programs such as Ananya using theory-informed, equity-sensitive (including gender), mixed-methods approaches can help elucidate causality and better explain pathways through which supply- and demand-side interventions contribute to changes in behaviour among the actors involved in the production of population-level health outcomes. Evidence from Bihar indicates that deep structural constraints in health system organisation and delivery of interventions pose substantial limitations on behaviour change among health care providers and beneficiaries. Study registration ClinicalTrials.gov number NCT02726230.

BACKGROUND CONTEXT Despite established guidelines, long-term management of surgically-treated low back pain (LBP) and lower extremity pain (LEP) remains heterogeneous. Understanding care heterogeneity could inform future approaches for standardization of practices. PURPOSE To describe treatment heterogeneity in surgically-managed LBP and LEP. STUDY DESIGN/SETTING Retrospective study of a nationwide commercial database spanning inpatient and outpatient encounters for enrollees of eligible employer-supplied healthcare plans (2007-2016). PATIENT SAMPLE A population-based sample of opioid-naive adult patients with newly-diagnosed LBP or LEP were identified. Inclusion required at least 12-months of pre-diagnosis and post-diagnosis continuous follow-up. EXPOSURE Included treatments/evaluations include conservative management (chiropractic manipulative therapy, physical therapy, epidural steroid injections), imaging (x-ray, MRI, CT), pharmaceuticals (opioids, benzodiazepines), and spine surgery (decompression, fusion). OUTCOME MEASURES Primary outcomes-of-interest were 12-month net healthcare expenditures (inpatient and outpatient) and 12-month opioid usage. METHODS Analyses include interrogation of care sequence heterogeneity and temporal trends in sequence-initiating services. Comparisons were conducted in the framework of sequence-specific treatment sequences, which reflect the personalized order of healthcare services pursued by each patient. Outlier sequences characterized by high opioid use and costs were identified from frequently observed surgical treatment sequences using Mahalanobis distance. RESULTS A total of 2,496,908 opioid-naive adult patients with newly-diagnosed LBP or LEP were included (29,519 surgical). In the matched setting, increased care sequence heterogeneity was observed in surgical patients (0.51 vs. 0.12 previously-unused interventions/studies pursued per month). Early opioid and MRI use has decreased between 2008 and 2015 but is matched by increases in early benzodiazepine and x-ray use. Outlier sequences, characterized by increased opioid use and costs, were found in 5.8% of surgical patients. Use of imaging prior to conservative management was common in patients pursuing outlier sequences compared to non-outlier sequences (96.5% vs. 63.8%, p

INTRODUCTION Infections are a leading cause of mortality and morbidity in preschool children. We aimed to assess the impact of the co-occurrence of cesarean section, early birth and formula feeding on hospitalization with infection in early childhood. MATERIAL AND METHODS Population-based retrospective record-linkage cohort study of 488 603 singleton livebirths ≥32 weeks' gestational age in New South Wales, Australia, 2007-2012. Multivariable Cox-regression was used to estimate independent and combined adjusted associations of gestational age, mode of birth (vaginal or cesarean section by labor onset) and formula feeding with time to first and repeat hospitalization with infection for children less than five years of age. RESULTS In all, 95 346 (19.5%) children were hospitalized with infection, and of these 24.8% (23 615) more than once. Median age at first and repeat hospitalization was 1.1 and 1.7 years, respectively. Earlier gestation, modes of birth other than spontaneous vaginal, and formula feeding were independently associated with an increased risk of first and repeat hospitalization with infection. At 32-36 weeks' gestation, co-occurrence of perinatal factors (cf. spontaneous vaginal birth at 39+ weeks without formula feeding) was associated with a 2-fold and 1.5-fold increased risk of first and repeat hospitalization, respectively. For births at 37-38 weeks, the increased risk was 1.5-fold and 1.25-fold for first and repeat hospitalization, respectively. CONCLUSIONS Cesarean section, labor induction, birth at

An iterative approach is proposed to predict the optimal concentration profiles in an adsorption process and to simultaneously obtain parameters for a multicomponent isotherm by selecting representative liquid compositions for experimental measurements. The proposed approach was demonstrated for xylene adsorption on zeolite 13X that has undergone a barium ion exchange. Breakthrough experiments were performed at liquid compositions predicted by the process model, which was refined in an iterative manner with the experimental data. Robustness of the isotherm parameters for model uncertainty and variations in the process design were also analyzed.

The objective of this study is to determine child health, development and educational outcomes for infants born following preterm prelabor rupture of the membrane (PPROM). Population-based record linkage cohort study using data from NSW, Australia, 2001 to 2014. Of 121 822 births at 20 to 37 weeks, 18 799 (15%) followed PPROM, 56 406 (46%) followed spontaneous labor and 46 617 (38%) were planned. Compared with infants of a similar gestational age born following spontaneous labor or planned delivery, exposure to PPROM did not increase the risk of childhood mortality, childhood hospitalization, developmentally vulnerable at school entry, low reading or numeracy scores. Median latency ranged from 12 days (interquartile range 3 to 37 days) at 25 weeks to 1 day (0 to 2 days) at 36 weeks. Longer latency and more advanced gestational age at birth were associated with better outcomes. Infants born following PPROM are at no greater risk of adverse child health, development and education outcomes than those of similar gestational age born without PPROM.

Background Male genital anomalies often require surgery in early life to address functional and cosmetic consequences. However, there has been little assessment of developmental outcomes of affected boys. Methods We conducted a population-based cohort study of all boys born in New South Wales, Australia, and undergoing school-entry developmental assessment in 2009 or 2012. Health and developmental information was obtained by means of record-linkage of birth, hospital and Australian Early Development Census data. Boys with hypospadias or undescended testis (UDT) were compared with those without. Developmental outcomes were assessed in five domains (physical health, emotional maturity, communication, cognitive skills, and social competence), and boys were categorized as vulnerable (

Approximately 1.7 million youth suffer from debilitating chronic pain in the US alone, conferring risk of continued pain in adulthood. Aberrations in threat-safety (T-S) discrimination are proposed to contribute to pain chronicity in adults and youth by interacting with pain-related distress. Yet, few studies have examined the neural circuitry underlying T-S discrimination in patients with chronic pain or how T-S discrimination relates to pain-related distress. In this study, 91 adolescents (10-24 years; 78 females) including 30 chronic pain patients with high pain-related distress, 29 chronic pain patients with low pain-related distress, and 32 healthy peers without chronic pain completed a developmentally appropriate T-S learning paradigm. We measured self-reported fear, psychophysiology (skin conductance response), and functional magnetic resonance imaging responses (N = 72 after functional magnetic resonance imaging exclusions). After controlling for age and anxiety symptoms, patients with high pain-related distress showed altered self-reported fear and frontolimbic activity in response to learned threat and safety cues compared with both patients with low pain-related distress and healthy controls. Specifically, adolescent patients with high pain-related distress reported elevated fear and showed elevated limbic (hippocampus and amygdala) activation in response to a learned threat cue (CS+). In addition, they showed decreased frontal (vmPFC) activation and aberrant frontolimbic connectivity in response to a learned safety cue (CS-). Patients with low pain-related distress and healthy controls appeared strikingly similar across brain and behavior. These findings indicate that altered T-S discrimination, mediated by frontolimbic activation and connectivity, may be one mechanism maintaining pain chronicity in adolescents with high levels of pain-related distress.

Background: Atrial fibrillation (AF) increases the risk of stroke 5-fold and there is rising interest to determine if AF severity or burden can further risk stratify these patients, particularly for near-term events. Using continuous remote monitoring data from cardiac implantable electronic devices, we sought to evaluate if machine learned signatures of AF burden could provide prognostic information on near-term risk of stroke when compared to conventional risk scores. Methods and Results: We retrospectively identified Veterans Health Administration serviced patients with cardiac implantable electronic device remote monitoring data and at least one day of device-registered AF. The first 30 days of remote monitoring in nonstroke controls were compared against the past 30 days of remote monitoring before stroke in cases. We trained 3 types of models on our data: (1) convolutional neural networks, (2) random forest, and (3) L1 regularized logistic regression (LASSO). We calculated the CHA 2 DS 2 -VASc score for each patient and compared its performance against machine learned indices based on AF burden in separate test cohorts. Finally, we investigated the effect of combining our AF burden models with CHA 2 DS 2 -VASc. We identified 3114 nonstroke controls and 71 stroke cases, with no significant differences in baseline characteristics. Random forest performed the best in the test data set (area under the curve [AUC]=0.662) and convolutional neural network in the validation dataset (AUC=0.702), whereas CHA 2 DS 2 -VASc had an AUC of 0.5 or less in both data sets. Combining CHA 2 DS 2 -VASc with random forest and convolutional neural network yielded a validation AUC of 0.696 and test AUC of 0.634, yielding the highest average AUC on nontraining data. Conclusions: This proof-of-concept study found that machine learning and ensemble methods that incorporate daily AF burden signature provided incremental prognostic value for risk stratification beyond CHA 2 DS 2 -VASc for near-term risk of stroke.

Physicians currently spend as much as half of their day in front of the computer. The Electronic Health Record (EHR) has been associated with declining bedside skills and physician burnout. Medical student EHR use has not been well studied or characterized. However, student responsibilities for EHR documentation will likely increase as the Centers for Medicare and Medicaid Services (CMS) most recent provisions now allow student notes for billing which will likely increase the role of medical student use of the EHR over time. To gain a better understanding of how medical students use the EHR at our institution, we retrospectively analyzed 6,692,994 EHR interactions from 49 third-year clerkship medical students and their supervising physicians assigned to the inpatient medicine ward rotation between June 25 2015 and June 24 2016 at a tertiary academic medical center. Medical students spent 4.42 hours (37%) of each day at the on the EHR and 35 minutes logging in from home. Improved understanding of student EHR-use and the effects on well-being warrants further attention, especially as EHR use increases with early trainees.

BACKGROUND: The morbidity and mortality associated with opioid and benzodiazepine co-prescription is a pressing national concern. Little is known about patterns of opioid and benzodiazepine use in patients with acute low back pain or lower extremity pain. OBJECTIVE: To characterize patterns of opioid and benzodiazepine prescribing among opioid-naïve, newly diagnosed low back pain (LBP) or lower extremity pain (LEP) patients and to investigate the relationship between benzodiazepine prescribing and long-term opioid use. DESIGN/SETTING: We performed a retrospective analysis of a commercial database containing claims for more than 75 million enrollees in the USA. PARTICIPANTS: Participants were adult patients newly diagnosed with LBP or LEP between 2008 and 2015 who did not have a red flag diagnosis, had not received an opioid prescription in the 6 months prior to diagnosis, and had 12 months of continuous enrollment after diagnosis. MAIN OUTCOMES AND MEASURES: Among patients receiving at least one opioid prescription within 12 months of diagnosis, we defined discrete patterns of benzodiazepine prescribing—continued use, new use, stopped use, and never use. We tested the association of these prescription patterns with long-term opioid use, defined as six or more fills within 12 months. RESULTS: We identified 2,497,653 opioid-naïve patients with newly diagnosed LBP or LEP. Between 2008 and 2015, 31.9% and 11.5% of these patients received opioid and benzodiazepine prescriptions, respectively, within 12 months of diagnosis. Rates of opioid prescription decreased from 34.8% in 2008 to 27.0% in 2015 (P

Importance Through prescription writing, dental clinicians are a potential source of initial opioid exposure and subsequent abuse for adolescents and young adults. Objective To examine the association between index dental opioid prescriptions from dental clinicians for opioid-naive adolescents and young adults in 2015 and new persistent use and subsequent diagnoses of abuse in this population. Design, Setting, and Participants This retrospective cohort study examined outpatient opioid prescriptions for patients aged 16 to 25 years in the Optum Research Database in 2015. Prescriptions were linked by National Provider Identifier number to a clinician category. Exposures Individuals were included in the index dental opioid (opioid-exposed) cohort if they filled an opioid prescription from a dental clinician in 2015, had continuous health plan coverage and no record of opioid prescriptions for 12 months before receiving the prescription, and had 12 months of health plan coverage after receiving the prescription. Two age- and sex-matched opioid-nonexposed control individuals were selected for each opioid-exposed individual and were assigned a corresponding phantom prescription date. Main Outcomes and Measures Receipt of an opioid prescription within 90 to 365 days, a health care encounter diagnosis associated with opioid abuse within 365 days, and all-cause mortality within 365 days of the index opioid or phantom prescription date. Results Among 754 002 individuals with continuous enrollment in 2015, 97 462 patients (12.9%) received 1 or more opioid prescriptions, of whom 29 791 (30.6%) received prescriptions supplied by a dental clinician. The opioid-exposed cohort included 14 888 participants (7882 women [52.9%], 11 273 white [75.7%], with mean [SD] age, 21.8 [2.4] years), and the randomly selected opioid-nonexposed cohort included 29 776 participants (15 764 women [52.9%], 20 078 [67.4%] white, with mean [SD] age, 21.8 [2.4] years). Among the 14 888 individuals in the index dental opioid cohort, 1021 (6.9%) received another opioid prescription 90 to 365 days later compared with 30 of 29 776 (0.1%) opioid-nonexposed controls (adjusted absolute risk difference, 6.8%; 95% CI, 6.3%-7.2%), and 866 opioid-exposed individuals (5.8%) experienced 1 or more subsequent health care encounters with an opioid abuse–related diagnosis compared with 115 opioid-nonexposed controls (0.4%) (adjusted absolute risk difference, 5.3%; 95% CI, 5.0%-5.7%). There was only 1 death in each cohort. Conclusions and Relevance The findings suggest that a substantial proportion of adolescents and young adults are exposed to opioids through dental clinicians. Use of these prescriptions may be associated with an increased risk of subsequent opioid use and abuse.

This paper presents a constructive proof of the existence of a regular non-atomic strictly-positive measure on any second-countable non-atomic locally compact Hausdorff space. This construction involves a sequence of finitely-additive set functions defined recursively on an ascending sequence of rings of subsets with a premeasure limit that is extendable to a measure with the desired properties. Non-atomicity of the space provides a non-trivial way to ensure that the limit is a premeasure., 11 to 12 pages total, 1 figure

To provide biologic insights into mechanisms underlying myelodysplastic syndromes (MDS) we evaluated the CD34+ marrow cells transcriptome using high-throughput RNA sequencing (RNA-Seq). We demonstrated significant differential gene expression profiles (GEPs) between MDS and normal and identified 41 disease classifier genes. Additionally, two main clusters of GEPs distinguished patients based on their major clinical features, particularly between those whose disease remained stable vs patients who transformed into acute myeloid leukemia within 12 months. The genes whose expression was associated with disease outcome were involved in functional pathways and biologic processes highly relevant for MDS. Combined with exomic analysis we identified differential isoform usage of genes in MDS mutational subgroups, with consequent dysregulation of distinct biological functions. This combination of clinical, transcriptomic and exomic findings provides valuable understanding of mechanisms underlying MDS and its progression to a more aggressive stage and also facilitates prognostic characterization of MDS patients.

OBJECTIVES: Investigate the association between severe neonatal morbidity (SNM) and child development and school performance among term infants. METHODS: The study population included term infants without major congenital conditions born between 2000 and 2007 in New South Wales, Australia, with a linked record of developmental assessment at ages 4 to 6 years in 2009 or 2012 (n = 144 535) or school performance at ages 7 to 9 years from 2009 to 2014 (n = 253 447). Developmental outcomes included special needs or being vulnerable and/or at risk in 1 of 5 developmental domains. School performance outcomes were test exemption, or performing RESULTS: Overall, 2.1% of infants experienced SNM. The adjusted odds ratio (95% confidence interval) for SNM and physical health was 1.18 (1.08–1.29), 1.14 (1.02–1.26) for language and cognitive skills, and 1.14 (1.06–1.24) and 1.13 (1.05–1.21) for scoring CONCLUSIONS: Term infants with SNM have greater odds of poor neurodevelopment in childhood. These findings provide population-based information for families and can inform clinical counseling and guidelines for follow-up and early intervention.

This study aimed to describe the utility of probabilistic record linkage of development and school performance data to a large population-based birth cohort and other administrative health datasets, and to assess whether any systematic differences exist between the records that did and did not link in each dataset

PURPOSE: To investigate how biologic age (phenotypic age at which your body functions) greater than chronologic age, (age acceleration (AgeAccel)), correlates with oocyte yield. METHODS: Thirty-nine women undergoing ovarian stimulation, inclusive of all infertility diagnoses, were included in this pilot study. Methylome analysis of peripheral blood was utilized to determine biologic age. AgeAccel was defined as biologic age > 2 years older than chronologic age. A negative binomial model was used to obtain the crude association of AgeAccel with number of oocytes. A parsimonious adjusted model for the number of oocytes was obtained using backwards selection (p

Summary We determined brain to liver weight ratio (BLWR) thresholds for fetal growth restriction (FGR) using autopsy information on 395 perinatal deaths comprising stillborn babies who died during labour and neonatal deaths. FGR was defined using two methods: (1) birth weight for gestational age (WGA) less than the 10th percentile; and (2) WGA less than the 10th percentile or discordant birth weight/length. The association between BLWR and FGR was investigated using odds ratios, and classification statistics were calculated for a range of BLWR thresholds. Using WGA, 84 cases (21.3%) were FGR and a further 15 cases (n = 99, 25%) had discordant birth weight/length. The BLWR ranged from 1.02 to 7.30 and was positively associated with FGR. BLWR was not associated with FGR for babies with congenital central nervous system or chromosomal abnormalities. Excluding these, for FGR defined using WGA and discordant birth weight/length, a BLWR threshold of 5.0 was 100% predictive of FGR. A BLWR threshold of 3.0 for babies over 28 weeks gestation and 3.7 for more preterm babies optimised case detection while minimising missed and false positive cases. Additional evidence of FGR should be sought for babies with a BLWR of less than 5.0 to confirm FGR.

ObjectivesFetal growth and development is a continuum with the optimal time of birth at 39-40 weeks gestation. Internationally, significant changes in clinical practice have seen planned birth (labour induction or pre­labour caesarean section) before 40 completed weeks gestation increase. Fetal brain development accelerates rapidly in the later stages of pregnancy from 32 weeks gestation, making it vulnerable to disruption from even slightly shortened gestation. This study aimed to investigate the association of gestational age and mode of birth with early childhood development. ApproachThis study utilised a population-based record-linkage of administrative birth, hospital and development data to obtain a cohort of 153,730 live born infants in New South Wales, Australia. These infants were born between 2002 and 2007, with a gestational age of at least 32 weeks and had an early development assessment in their first year of school in 2009 or 2012. Childhood development was assessed in five main domains (physical health and wellbeing, language and cognitive skills, social competence, emotional maturity, and communication skills and general knowledge) with each comprised of a number of sub-domains. Children with a score below the 10th percentile nationally are considered developmentally vulnerable (DV) in that domain. Children who were DV for two or more of the five main domains are classified as developmentally high risk (DHR) and this was the primary study outcome. Robust multivariable Poisson models were used to obtain individual and combined relative risks for gestational age and mode of birth with DHR, adjusted for maternal demographic, socio-economic, perinatal, and child characteristics. ResultsOverall, 9.6% of children were DHR. The adjusted relative risk (aRR) (95% confidence interval) of being DHR decreased with increasing gestational age (referent: 40 weeks); 32-33 weeks 1.25 (1.08-1.44), 34­-36 weeks 1.26 (1.18-1.34), 37 weeks 1.17 (1.10-1.25), 38 weeks 1.06 (1.01-­1.10), 39 weeks 0.98 (0.94-1.02), 41+ weeks 0.99 (0.94-­1.03) and for planned birth (referent: vaginal birth following spontaneous labour), 1.07 (1.04­-1.11). The aRR for planned birth at 37 weeks was 1.26 (1.18-­1.34) and at 38 weeks 1.13 (1.08-­1.19). ConclusionEarly (

Key Points Question Does the prevalence of neuraxial labor analgesia vary across US states? Findings In this population-based, cross-sectional analysis of 2 625 950 pregnant women who underwent labor, Maine had the lowest adjusted neuraxial analgesia prevalence (36.6%) and Nevada the highest (80.1%). The odds of receiving neuraxial analgesia were 1.5-fold higher if the same patient received neuraxial analgesia in a high-use vs a low-use state; and 5.4% of the overall variation in neuraxial analgesia prevalence is explained by US state. Meaning Results of this study suggest that wide variation exists in neuraxial analgesia use across US states, with a small portion of the overall variation explained by US states., This population-based, cross-sectional analysis using US birth certificate data examines variation in prevalence of neuraxial labor analgesia among US states., Importance Neuraxial labor analgesia is recognized as the most effective method of providing pain relief during labor. Little is known about variation in the rates of neuraxial analgesia across US states. Identifying the presence and extent of variation may provide insights into practice variation and may indicate where access to neuraxial analgesia is inadequate. Objective To test the hypothesis that variation exists in neuraxial labor analgesia use among US states. Design, Setting, and Participants Retrospective, population-based, cross-sectional analysis using US birth certificate data. Participants were 2 625 950 women who underwent labor in 2015. Main Outcomes and Measures State-specific prevalence of neuraxial analgesia per 100 women who underwent labor and variability in neuraxial analgesia use among states, assessed using multilevel multivariable regression modeling with the median odds ratio and the intraclass correlation coefficient to evaluate variation by state. Results In the study population of 2 625 950 women, 0.1% (n = 2010) were younger than 15 years, 7.0% (n = 183 546) were between the ages of 15 and 19 years, 23.6% (n = 620 118) were between the ages of 20 and 24 years, 29.6% (n = 777 957) were between the ages of 25 and 29 years, 26.0% (n = 683 656) were between the ages of 30 and 34 years, 11.4% (n = 298 237) were between the ages of 35 and 39 years, 2.2% (n = 57 130) were between the ages of 40 and 44 years, and 0.1% (n = 3296) were between the ages of 45 and 54 years. More than 90% were privately insured or insured with Medicaid. Neuraxial analgesia was used by 73.1% (n = 1 920 368) of women. After adjustment for antepartum, obstetric, and intrapartum factors, Maine had the lowest neuraxial analgesia prevalence (36.6%; 95% CI, 33.2%-40.1%) and Nevada the highest (80.1%; 95% CI, 78.3%-81.7%). The adjusted median odds ratio was 1.5 (95% CI, 1.4-1.6), and the intraclass correlation coefficient was 5.4% (95% CI, 4.0%-7.9%). Conclusions and Relevance Results of this study suggest that a small portion of the overall variation in neuraxial analgesia use is explained by US states. Unmeasured patient-level and hospital-level factors likely account for a large portion of the variation between states. Efforts should be made to understand what the main reasons are for this variation and whether the variation influences maternal or perinatal outcomes.

Key Points Question What are the nationwide patterns of health care utilization in patients newly diagnosed with low back and lower extremity pain? Findings In this cohort study of nearly 2.5 million US patients diagnosed with low back or lower extremity pain between 2008 and 2015, only 1.2% received surgery, but this subset of patients accounted for 29.3% of total 12-month costs. Many received care inconsistent with guidelines, such as early imaging. Meaning The findings suggest that few patients with new episodes of low back or lower extremity pain progress to surgery, and overimaging of low back or lower extremity pain is associated with a significant, avoidable cost burden for a condition that is typically self-limited., This cohort study examines health care utilization and expenditures among US adult patients with newly diagnosed low back pain or lower extremity pain treated surgically vs nonsurgically., Importance Low back pain (LBP) with or without lower extremity pain (LEP) is one of the most common reasons for seeking medical care. Previous studies investigating costs in this population targeted patients receiving surgery. Little is known about health care utilization among patients who do not undergo surgery. Objectives To assess use of health care resources for LBP and LEP management and analyze associated costs. Design, Setting, and Participants This cohort study used a retrospective analysis of a commercial database containing inpatient and outpatient data for more than 75 million individuals. Participants were US adults who were newly diagnosed with LBP or LEP between 2008 and 2015, did not have a red-flag diagnosis, and were opiate naive prior to diagnosis. Dates of analysis were October 6, 2018, to March 7, 2019. Exposures Newly diagnosed LBP or LEP. Main Outcomes and Measures The primary outcome was total cost of care within the first 6 and 12 months following diagnosis, stratified by whether patients received spinal surgery. An assessment was performed to determine whether patients who did not undergo surgery received care in accordance with proposed guidelines for conservative LBP and LEP management. Costs resulting from use of different health care services were estimated. Results A total of 2 498 013 adult patients with a new LBP or LEP diagnosis (median [interquartile range] age, 47 [36-58] years; 1 373 076 [55.0%] female) were identified. More than half (55.7%) received no intervention. Only 1.2% of patients received surgery, but they accounted for 29.3% of total 12-month costs ($784 million). Total costs of care among the 98.8% of patients who did not receive surgery were $1.8 billion. Patients who did not undergo surgery frequently received care that was inconsistent with clinical guidelines for LBP and LEP: 32.3% of these patients received imaging within 30 days of diagnosis and 35.3% received imaging without a trial of physical therapy. Conclusions and Relevance The findings suggest that surgery is rare among patients with newly diagnosed LBP and LEP but remains a significant driver of spending. Early imaging in patients who do not undergo surgery was also a major driver of increased health care expenditures. Avoidable costs among patients with typically self-limited conditions result in considerable economic burden to the US health care system.

By creating a seamless facility that utilizes new mechanical technology, as well as maintaining an increased nurse-to-patient ratio, will exemplify the efficiency and function with in health care architecture, that can benefit all occupants of the facility.

The resolution of racemic gas mixtures by simulated moving bed (SMB) and pressure swing adsorption (PSA) is investigated by dynamic simulation and optimization. Enantiomer separation of inhalation anesthetics is important because there is evidence that the purified enantiomers may have different pharmacological properties than the racemate. The model parameters reported in an experimental investigation performed elsewhere are used to study the feasibility of this separation using SMB and PSA configurations. Both processes were modeled in gPROMS® as systems of differential algebraic equations. Operating conditions are optimized such that the feed throughput and product recovery for each process were maximized subject to equal constraints on the pressures and superficial gas velocities. SMB was found to be capable of resolving racemic feed mixtures with purity and recovery exceeding 99%. On the other hand, PSA was also able to provide a single purified enantiomer with low recovery of about 30% which may limit its application to enantiomer separation. Nevertheless, PSA consumes less desorbent, and achieves higher throughput at the sacrifice of lower recovery.

Importance Critically ill patients often receive high-intensity life sustaining treatments (LST) in the intensive care unit (ICU), although they can be ineffective and eventually undesired. Determining the risk factors associated with reversals in LST goals can improve patient and provider appreciation for the natural history and epidemiology of critical care and inform decision making around the (continued) use of LSTs. Methods This is a single institution retrospective cohort study of patients receiving life sustaining treatment in an academic tertiary hospital from 2009 to 2013. Deidentified patient electronic medical record data was collected via the clinical data warehouse to study the outcomes of treatment limiting Comfort Care and do-not-resuscitate (DNR) orders. Extended multivariable Cox regression models were used to estimate the association of patient and clinical factors with subsequent treatment limiting orders. Results 10,157 patients received life-sustaining treatment while initially Full Code (allowing all resuscitative measures). Of these, 770 (8.0%) transitioned to Comfort Care (with discontinuation of any life-sustaining treatments) while 1,669 (16%) patients received new DNR orders that reflect preferences to limit further life-sustaining treatment options. Patients who were older (Hazard Ratio(HR) 1.37 [95% CI 1.28–1.47] per decade), with cerebrovascular disease (HR 2.18 [95% CI 1.69–2.81]), treated by the Medical ICU (HR 1.92 [95% CI 1.49–2.49]) and Hematology-Oncology (HR 1.87 [95% CI 1.27–2.74]) services, receiving vasoactive infusions (HR 1.76 [95% CI 1.28, 2.43]) or continuous renal replacement (HR 1.83 [95% CI 1.34, 2.48]) were more likely to transition to Comfort Care. Any new DNR orders were more likely for patients who were older (HR 1.43 [95% CI 1.38–1.48] per decade), female (HR 1.30 [95% CI 1.17–1.44]), with cerebrovascular disease (HR 1.45 [95% CI 1.25–1.67]) or metastatic solid cancers (HR 1.92 [95% CI 1.48–2.49]), or treated by Medical ICU (HR 1.63 [95% CI 1.42–1.86]), Hematology-Oncology (HR 1.63 [95% CI 1.33–1.98]) and Cardiac Care Unit-Heart Failure (HR 1.41 [95% CI 1.15–1.72]). Conclusion Decisions to reverse or limit treatment goals occurs after more than 1 in 13 trials of LST, and is associated with older female patients, receiving non-ventilator forms of LST, cerebrovascular disease, and treatment by certain medical specialty services.

Background Acute gastroenteritis (AGE) is a leading cause of infectious morbidity in childhood. Clinical studies have implicated caesarean section, early birth and formula feeding in modifying normal gut microbiota development and immune system homeostasis in early life. Rates of early birth and cesarean delivery are also increasing worldwide. This study aimed to investigate the independent and combined associations of the mode and timing of birth and breastmilk feeding with AGE hospitalisations in early childhood. Methods Population-based record-linkage study of 893,360 singleton livebirths of at least 33 weeks gestation without major congenital conditions born in hospital, New South Wales, Australia, 2001–2011. Using age at first AGE hospital admission, Cox-regression was used to estimate the associations for gestational age, vaginal birth or caesarean delivery by labour onset and formula-only feeding while adjusting for confounders. Results There were 41,274 (4.6 %) children admitted to hospital at least once for AGE and the median age at first admission was 1.4 years. Risk of AGE admission increased with decreasing gestational age (37–38 weeks: 15 % increased risk, 33–36 weeks: 25 %), caesarean section (20 %), planned birth (17 %) and formula-only feeding (18 %). The rate of AGE admission was highest for children who were born preterm by modes of birth other than vaginal birth following the spontaneous onset of labour and who received formula-only at discharge from birth care (62–78 %). Conclusions Vaginal birth following spontaneous onset of labour at 39+ weeks gestation with any breastfeeding minimised the risk of gastroenteritis hospitalisation in early childhood. Given increasing trends in early planned birth and caesarean section worldwide, these results provide important information about the impact obstetric interventions may have on the development of the infant gut microbiota and immunity. Electronic supplementary material The online version of this article (doi:10.1186/s12887-016-0591-0) contains supplementary material, which is available to authorized users.

Objective The aim of this study was to determine whether outcomes in a first pregnancy were associated with changes into and out of public maternity care. Methods The study population included 155492 women with first and second sequential singleton births, 2000–09 in New South Wales. Analyses were stratified by whether obstetric care for the first birth involved private or public maternity care. Interventions, infant and maternal outcomes were assessed as predictors of a change in care. Adjusted odds ratios for changing care were obtained from logistic regression using backwards elimination. Results Similar proportions of women changed from private to public care between first and second births (9.6% compared with 9.4% public to private, P-value = 0.10). Although interventions (operative delivery, epidural) and outcomes (low Apgar, preterm birth, perinatal death, postpartum haemorrhage, perineal tear and severe maternal morbidity) were all associated with changes from public to private care, only poor infant condition (adjusted odds ratio 1.39, 95% confidence interval 1.15–1.68) was associated with a change from private to public care. Conclusions The majority of women had consistent care type for both births. This may indicate that women are generally satisfied with care, they rationalise that their first birth care was optimal or they value continuity of carer across pregnancies. What is known about the topic? There is some evidence to suggest that interventions and outcomes of one pregnancy are associated with changes in type of delivery, timing of delivery and outcomes of subsequent births. What does this paper add? Obstetric interventions and adverse maternal and infant outcomes were associated with changing maternity care sector and influenced whether or not women remained with the same care provider. What are the implications for practitioners? Continuity of carer may be important to women in choosing their subsequent pregnancy maternity care sector. Most women do not change provider, but first-birth experiences appear to influence those who do change.