Publications by authors named "Jason Bentley"

52 Publications

Breastfeeding patterns and effects of minimal supplementation on breastfeeding exclusivity and duration in term infants: A prospective sub-study of a randomised controlled trial.

J Paediatr Child Health 2021 Mar 25. Epub 2021 Mar 25.

Child Population Health Research, Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Aim: Despite international recommendations, less than one-third of Australian women exclusively breastfeed for 6 months. The aims of this study were to prospectively determine rates and factors associated with the type and duration of breastfeeding in the first year and examine the effect of minimal supplementation.

Methods: We conducted a sub-study of a randomised controlled trial in Sydney, Australia, which included 635 women with uncomplicated term births who intended to breastfeed. Data were collected daily for 56 days, and then at 2, 6 and 12 months post-partum.

Results: Breastfeeding outcomes were evaluated for 553 (87%), 480 (76%) and 392 (62%) women at 2, 6 and 12 months. Exclusive breastfeeding was 81% at 2 months and 8% at 6 months. Partial breastfeeding was 75% at 6 months and 54% at 12 months. Factors associated with breastfeeding cessation included caesarean birth, low milk supply, problems latching, increased time to breastfeed, use of formula >7 days in the first 2 months, return to work and early introduction of solids. Breast pain in the first week was associated with a 10% decrease in exclusive breastfeeding. Cracked nipples and no previous breastfeeding experience were associated with supplementation of ≤7 days but had no effect on long-term breastfeeding duration.

Conclusions: Exclusive breastfeeding declined significantly between 2 and 6 months post-partum. Early intervention and education to prolong breastfeeding duration should include strategies to manage breast pain and nipple damage to minimise prolonged supplementation. Consistent guidelines about introduction of complementary foods, improved maternity leave and workplace incentives could be effective in prolonging breastfeeding.
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http://dx.doi.org/10.1111/jpc.15464DOI Listing
March 2021

Association of Gestational Age with Postpartum Hemorrhage.

Anesthesiology 2021 Mar 23. Epub 2021 Mar 23.

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.

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http://dx.doi.org/10.1097/ALN.0000000000003730DOI Listing
March 2021

Impact of the program on reproductive, maternal, newborn and child health and nutrition in Bihar, India: early results from a quasi-experimental study.

J Glob Health 2020 Dec 19;10(2):021002. Epub 2020 Dec 19.

Department of Global Health, George Washington University Milken Institute School of Public Health, Washington, D.C., USA.

Background: The Government of Bihar (GoB) in India, the Bill and Melinda Gates Foundation and several non-governmental organisations launched the 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 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 ; two-thirds (n = 13) of secular indicator changes were in a direction expected to promote health. Statistically significant impact attributable to the 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 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 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.
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http://dx.doi.org/10.7189/jogh.10.021002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757842PMC
December 2020

Trends in reproductive, maternal, newborn and child health and nutrition indicators during five years of piloting and scaling-up of interventions in Bihar, India.

J Glob Health 2020 Dec;10(2):021003

Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.

Background: The program in Bihar implemented household and community-level interventions to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) in two phases: a first phase of intensive ancillary support to governmental implementation and innovation testing by non-government organisation (NGO) partners in eight focus districts (2012-2014), followed by a second phase of state-wide government-led implementation with techno-managerial assistance from NGOs (2014 onwards). This paper examines trends in RMNCHN indicators in the program's implementation districts from 2012-2017.

Methods: Eight consecutive rounds of cross-sectional Community-based Household Surveys conducted by CARE India in 2012-2017 provided comparable data on a large number of indicators of frontline worker (FLW) performance, mothers' behaviours, and facility-based care and outreach service delivery across the continuum of maternal and child care. Logistic regression, considering the complex survey design and sample weights generated by that design, was used to estimate trends using survey rounds 2-5 for the first phase in the eight focus districts and rounds 6-9 for the second phase in all 38 districts statewide, as well as the overall change from round 2-9 in focus districts. To aid in contextualising the results, indicators were also compared amongst the formerly focus and the non-focus districts at the beginning of the second phase.

Results: In the first phase, the levels of 34 out of 52 indicators increased significantly in the focus districts, including almost all indicators of FLW performance in antenatal and postnatal care, along with mother's birth preparedness, some breastfeeding practices, and immunisations. Between the two phases, 33 of 52 indicators declined significantly. In the second phase, the formerly focus districts experienced a rise in the levels of 14 of 50 indicators and a decline in the levels of 14 other indicators. There was a rise in the levels of 22 out of 50 indicators in the non-focus districts in the second phase, with a decline in the levels of 13 other indicators.

Conclusions: Improvements in indicators were conditional on implementation support to program activities at a level of intensity that was higher than what could be achieved at scale so far. Successes during the pilot phase of intensive support suggests that RMNCHN can be improved statewide in Bihar with sufficient investments in systems performance improvements.

Study Registration: ClinicalTrials.gov number NCT02726230.
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http://dx.doi.org/10.7189/jogh.10.021003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757843PMC
December 2020

Evaluation of a large-scale reproductive, maternal, newborn and child health and nutrition program in Bihar, India, through an equity lens.

J Glob Health 2020 Dec 19;10(2):021011. Epub 2020 Dec 19.

Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.

Background: Despite increasing focus on health inequities in low- and middle income countries, significant disparities persist. We analysed impacts of a statewide maternal and child health program among the most compared to the least marginalised women in Bihar, India.

Methods: Utilising survey-weighted logistic regression, we estimated programmatic impact using difference-in-difference estimators from Mathematica data collected at the beginning (2012, n = 10 174) and after two years of program implementation (2014, n = 9611). We also examined changes in disparities over time using eight rounds of Community-based Household Surveys (CHS) (2012-2017, n = 48 349) collected by CARE India.

Results: At baseline for the Mathematica data, least marginalised women generally performed desired health-related behaviours more frequently than the most marginalised. After two years, most disparities persisted. Disparities increased for skilled birth attendant identification [+16.2% (most marginalised) vs +32.6% (least marginalized),  < 0.01) and skin-to-skin care (+14.8% vs +20.4%,  < 0.05), and decreased for immediate breastfeeding (+10.4 vs -4.9,  < 0.01). For the CHS data, odds ratios compared the most to the least marginalised women as referent. Results demonstrated that disparities were most significant for indicators reliant on access to care such as delivery in a facility (OR range: 0.15 to 0.48) or by a qualified doctor (OR range: 0.08 to 0.25), and seeking care for complications (OR range: 0.26 to 0.64).

Conclusions: Disparities observed at baseline generally persisted throughout program implementation. The most significant disparities were observed amongst behaviours dependent upon access to care. Changes in disparities largely were due to improvements for the least marginalised women without improvements for the most marginalised. Equity-based assessments of programmatic impacts, including those of universal health approaches, must be undertaken to monitor disparities and to ensure equitable and sustainable benefits for all.

Study Registration: ClinicalTrials.gov number NCT02726230.
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http://dx.doi.org/10.7189/jogh.10.021011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759017PMC
December 2020

Health layering of self-help groups: impacts on reproductive, maternal, newborn and child health and nutrition in Bihar, India.

J Glob Health 2020 Dec 19;10(2):021007. Epub 2020 Dec 19.

Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.

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 - - 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 JEEViKAHL, 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 ( 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 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 ( 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 (), 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.
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http://dx.doi.org/10.7189/jogh.10.021007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759023PMC
December 2020

Health impact of self-help groups scaled-up statewide in Bihar, India.

J Glob Health 2020 Dec 19;10(2):021006. Epub 2020 Dec 19.

Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.

Background: The objective of this study was to assess the impact of self-help groups (SHGs) and subsequent scale-up on reproductive, maternal, newborn, child health, and nutrition (RMNCHN) and sanitation outcomes among marginalised women in Bihar, India from 2014-2017.

Methods: We examined RMNCHN and sanitation behaviors in women who were members of any SHGs compared to non-members, without differentiating between types of SHGs. We analysed annual surveys across 38 districts of Bihar covering 62 690 women who had a live birth in the past 12 months. All analyses utilised data from Community-based Household Surveys (CHS) rounds 6-9 collected in 2014-2017 by CARE India as part of the Bihar Technical Support Program funded by the Bill & Melinda Gates Foundation. We examined 66 RMNCHN and sanitation indicators using survey logistic regression; the comparison group in all cases was age-comparable women from the geographic contexts of the SHG members but who did not belong to SHGs. We also examined links between discussion topics in SHGs and changes in relevant behaviours, and stratification of effects by parity and mother's age.

Results: SHG members had higher odds compared to non-SHG members for 60% of antenatal care indicators, 22% of delivery indicators, 70% of postnatal care indicators, 50% of nutrition indicators, 100% of family planning and sanitation indicators and no immunisation indicators measured. According to delivery platform, most FLW performance indicators (80%) had increased odds, followed by maternal behaviours (57%) and facility care and outreach service delivery (22%) compared to non-SHG members. Self-report of discussions within SHGs on specific topics was associated with increased related maternal behaviours. Younger SHG members (<25 years) had attenuated health indicators compared to older group members (≥25 years), and women with more children had more positive indicators compared to women with fewer children.

Conclusions: SHG membership was associated with improved RMNCHN and sanitation indicators at scale in Bihar, India. Further work is needed to understand the specific impacts of health layering upon SHGs. Working through SHGs is a promising vehicle for improving primary health care.

Study Registration: ClinicalTrials.gov number NCT02726230.
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http://dx.doi.org/10.7189/jogh.10.021006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761401PMC
December 2020

Impact of mHealth interventions for reproductive, maternal, newborn and child health and nutrition at scale: BBC Media Action and the program in Bihar, India.

J Glob Health 2020 Dec 19;10(2):021005. Epub 2020 Dec 19.

Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.

Background: Mobile health (mHealth) tools have potential for improving the reach and quality of health information and services through community health workers in low- and middle-income countries. This study evaluates the impact of an mHealth tool implemented at scale as part of the statewide reproductive,maternal, newborn and child health and nutrition (RMNCHN) program in Bihar, India.

Methods: Three survey-based data sets were analysed to compare the health-related knowledge, attitudes and behaviours amongst childbearing women exposed to the Mobile and Dr. Anita mHealth tools during their visits with frontline workers compared with those who were unexposed.

Results: An evaluation by Mathematica (2014) revealed that exposure to Mobile and Dr. Anita recordings were associated with significantly higher odds of consuming iron-folic acid tablets (odds ratio (OR) = 2.3, 95% confidence interval (CI) = 1.8-3.1) as well as taking a set of three measures for delivery preparedness (OR = 2.8, 95% CI = 1.9-4.2) and appropriate infant complementary feeding (OR = 1.9, 95% CI = 1.0-3.5). CARE India's Community-based Household Surveys (2012-2017) demonstrated significant improvements in early breastfeeding (OR = 1.64, 95% CI = 1.5-1.78) and exclusive breastfeeding (OR = 1.46, 95% CI = 1.33-1.62) in addition to birth preparedness practices. BBC Media Action's Usage & Engagement Survey (2014) demonstrated a positive association between exposure to Mobile and Dr. Anita and exclusive breastfeeding (58% exposed vs 43% unexposed,  < 0.01) as well as maternal respondents' trust in their frontline worker.

Conclusions: Significant improvements in RMNCHN-related knowledge and behaviours were observed for Bihari women who were exposed to Mobile and Dr. Anita. This analysis is unique in its rigorous evaluation across multiple data sets of mHealth interventions implemented at scale. These results can help inform global understanding of how best to use mHealth tools, for whom, and in what contexts.

Study Registration: ClinicalTrials.gov number NCT02726230.
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http://dx.doi.org/10.7189/jogh.10.021005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758913PMC
December 2020

Improving primary health care delivery in Bihar, India: Learning from piloting and statewide scale-up of .

J Glob Health 2020 Dec;10(2):021001

CARE India, Patna, India.

In 2010, the Bill and Melinda Gates Foundation (BMGF) partnered with the Government of Bihar (GoB), India to launch the program to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) outcomes. The program sought to address supply- and demand-side barriers to the adoption, coverage, quality, equity and health impact of select RMNCHN interventions. Approaches included strengthening frontline worker service delivery; social and behavior change communications; layering of health, nutrition and sanitation into women's self-help groups (SHGs); and quality improvement in maternal and newborn care at primary health care facilities. program interventions were piloted in approximately 28 million population in eight innovation districts from 2011-2013, and then beginning in 2014, were scaled up by the GoB across the rest of the state's population of 104 million. A Bihar Technical Support Program provided techno-managerial support to governmental Health as well as Integrated Child Development Services, and the JEEViKA Technical Support Program supported health layering and scale-up of the GoB's SHG program. The level of support at the block level during statewide scale-up in 2014 onwards was approximately one-fourth that provided in the pilot phase of in 2011-2013. This paper - the first manuscript in an 11-manuscript and 2-viewpoint collection on Learning from Lessons for primary health care performance improvement - seeks to provide a broad description of and subsequent statewide adaptation and scale-up, and capture the background and context, key objectives, interventions, delivery approaches and evaluation methods of this expansive program. Subsequent papers in this collection focus on specific intervention delivery platforms. For the analyses in this series, Stanford University held key informant interviews and worked with the technical support and evaluation grantees of the program, as well as leadership from the India Country Office of the BMGF, to analyse and synthesise data from multiple sources. Capturing lessons from the pilot program and statewide scale-up will assist program managers and policymakers to more effectively design and implement RMNCHN programs at scale through technical assistance to governments.
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http://dx.doi.org/10.7189/jogh.10.021001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757841PMC
December 2020

Inpatient Observation After Transition From Intravenous to Oral Antibiotics.

Hosp Pediatr 2020 07 12;10(7):591-599. Epub 2020 Jun 12.

Lucile Packard Children's Hospital Stanford, Stanford, California; and.

Objectives: Children hospitalized with infections are commonly transitioned from intravenous (IV) to enteral (per os [PO]) antibiotics before discharge, after which they may be observed in the hospital to ensure tolerance of PO therapy and continued clinical improvement. We sought to describe the frequency and predictors of in-hospital observation after transition from IV to PO antibiotics in children admitted for skin and soft tissue infections (SSTIs).

Methods: We conducted a retrospective cohort study of children with SSTIs discharged between January 1, 2016, and June 30, 2018, using the Pediatric Health Information System database. Children were classified as observed if hospitalized ≥1 day after transitioning from IV to PO antibiotics. We calculated the proportion of observed patients and used logistic regression with random intercepts to identify predictors of in-hospital observation.

Results: Overall, 15% (558 of 3704) of hospitalizations for SSTIs included observation for ≥1 hospital day after the transition from IV to PO antibiotics. The proportion of children observed differed significantly between hospitals (range of 4%-27%; < .001). Observation after transition to PO antibiotics was less common in older children (adjusted odds ratio [aOR] = 0.69; 95% confidence interval [CI] 0.52-0.90; = .045). Children initially prescribed vancomycin (aOR = 1.36; 95% CI 1.03-1.79; = .032) or with infections located on the neck (aOR = 1.72; 95% CI 1.32-2.24; < .001) were more likely to be observed.

Conclusions: Children hospitalized for SSTIs are frequently observed after transitioning from IV to PO antibiotics, and there is substantial variability in the observation rate between hospitals. Specific factors predict in-hospital observation and should be investigated as part of future studies aimed at improving the care of children hospitalized with SSTIs.
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http://dx.doi.org/10.1542/hpeds.2020-0047DOI Listing
July 2020

Timing and Predictors of Subspecialty Career Choice Among Internal Medicine Residents: A Retrospective Cohort Study.

J Grad Med Educ 2020 Apr;12(2):212-216

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.
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http://dx.doi.org/10.4300/JGME-D-19-00556.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161324PMC
April 2020

Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield.

J Assist Reprod Genet 2020 May 13;37(5):1097-1103. Epub 2020 Apr 13.

Department of Reproductive Endocrinology & Infertility, Stanford Hospital and Clinics, Stanford, CA, USA.

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 < 0.05).

Results: Measures of age were negatively correlated with number of oocytes (chronological age Pearson ρ = - 0.45, biologic age Pearson ρ = - 0.46) and AMH was positively correlated with number of oocytes (Pearson ρ = 0.91). Patients with AgeAccel were noted to have lower AMH values (1.29 ng/mL vs. 2.29, respectively (p = 0.049)) and lower oocyte yield (5.50 oocytes vs. 14.50 oocytes, respectively (p = 0.0030)). A crude association of a 7-oocyte reduction in the age-accelerated group was found (- 6.9 oocytes (CI - 11.6, - 2.4)). In a model with AMH and antral follicle count, AgeAccel was associated with a statistically significant 3.3 reduction in the number of oocytes (- 3.1; 95% CI - 6.5, - 0.1; p = 0.036).

Conclusions: In this small pilot study, AgeAccel is associated with a lower AMH and lower oocyte yield providing preliminary evidence that biologic age, specifically AgeAccel, may serve as an epigenetic biomarker to improve the ability of predictive models to assess ovarian reserve.
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http://dx.doi.org/10.1007/s10815-020-01763-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244694PMC
May 2020

Portable Ultrasound Device Usage and Learning Outcomes Among Internal Medicine Trainees: A Parallel-Group Randomized Trial.

J Hosp Med 2020 Feb 11;15(2):e1-e6. Epub 2020 Feb 11.

Department of Medicine, Stanford University School of Medicine, Stanford, California.

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.
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http://dx.doi.org/10.12788/jhm.3351DOI Listing
February 2020

Variation in Rate of Attention-Deficit/Hyperactivity Disorder Management by Primary Care Providers.

Acad Pediatr 2020 04 30;20(3):384-390. Epub 2019 Nov 30.

Division of Developmental-Behavioral Pediatrics (Y Bannett, HM Feldman, DA Ansel, and LC Huffman), Stanford University School of Medicine, Stanford, Calif.

Objective: To describe variation in rates of attention-deficit/hyperactivity disorder (ADHD) management by pediatrics primary care providers (PCPs) and to assess influence of clinician characteristics on variation.

Methods: Retrospective cohort study of electronic health records from all office visits of patients aged 4 to 17 years seen at least twice between 2015 and 2017 by 73 clinicians in 9 pediatrics practices of a community-based primary health care network in California. Outcomes per clinician: 1) percent patients seen for ADHD management; (2) percent ADHD patients with diagnosed comorbid conditions. Logistic random-effects regression models examined practice- and clinician-level variation.

Results: Of 40,323 patients in the cohort, 2039 (5.1%) carried an ADHD diagnosis, of which 1142 (56%) received ADHD medication. Percent of patients seen for ADHD management varied by clinician from 0.0% to 8.3% (median 3.0%). After accounting for practice-level variation and patient characteristics (ie, sex, age, insurance), clinician characteristics explained 28% of clinician variation in ADHD management. ADHD management rate was associated with high-percent full-time equivalent (odds ratio 1.17; 95% confidence interval 1.07-1.27). Percent of ADHD patients with diagnoses of comorbidities varied by clinician from 0.0% to 100% (median 35%). Association between ADHD management rate and comorbidity diagnosis was minimal (R = 0.10).

Conclusions: Objective electronic health records measures showed that PCPs in this network varied widely in their involvement in ADHD management. For most PCPs, percent of patients with ADHD and diagnosis of comorbidities was lower than estimated prevalence rates. Exploration of modifiable factors associated with PCP variation is needed to inform strategies for implementation of evidence-based practices.
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http://dx.doi.org/10.1016/j.acap.2019.11.016DOI Listing
April 2020

Brain signatures of threat-safety discrimination in adolescent chronic pain.

Pain 2020 03;161(3):630-640

Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Palo Alto, CA, United States.

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.
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http://dx.doi.org/10.1097/j.pain.0000000000001753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018610PMC
March 2020

A randomized, placebo-controlled crossover trial of phentermine-topiramate ER in patients with binge-eating disorder and bulimia nervosa.

Int J Eat Disord 2020 02 13;53(2):266-277. Epub 2019 Nov 13.

Najarian Center for Obesity, Los Osos, California.

Objective: Open trials suggest phentermine/topiramate ER (PHEN/TPM-ER), food and drug administration (FDA) approved for obesity, has utility for binge eating. With no randomized controlled trials (RCTs) yet performed, this trial aimed to evaluate PHEN/TPM-ERs efficacy and safety in a crossover RCT for patients with binge-eating disorder (BED) or bulimia nervosa (BN).

Method: Participants were randomized to 12-weeks PHEN/TPM-ER (3.75 mg/23 mg-15 mg/92 mg) or placebo followed by 2-weeks drug washout, then 12-week crossover. Demographics, vitals, eating disorder behaviors, mood, and side effects were measured. Primary outcome was objective binge-eating (OBE) days/4-weeks; secondary outcomes included binge abstinence. Mixed-effect models estimated treatment effects, with fixed effects adjusting for treatment, study period, and diagnosis.

Results: The 22 adults (BED = 18, BN = 4) were female (96%), Caucasian (55%), aged 42.9 (SD = 10.1) years with body mass index = 31.1 (SD = 6.2) kg/m . Baseline OBE days/4-weeks decreased from 16.2 (SD = 7.8) to 4.2 (SD = 8.4) after PHEN/TPM-ER versus 13.2 (SD = 9.1) after placebo (p < .0001), with abstinence rates = 63.6% on PHEN/TPM-ER versus 9.1% on placebo (p < .0001). Weight changes = -5.8 kg on PHEN/ TPM-ER versus +0.4 kg on placebo. Drop-out = 2 (9%) on PHEN/TPM-ER and 2 (9%) on placebo, with few side effects. Vital sign changes with PHEN/TPM-ER were minimal and similar to placebo. Responses were not significantly different for BED versus BN.

Discussion: This first RCT to evaluate the efficacy and safety of PHEN/TPM-ER for BED/BN found this drug combination significantly more effective at reducing binge eating than placebo and well tolerated. However, with only four participants with BN, findings regarding the safety of PHEN/TPM-ER in patients with BN must be taken with caution.

Trial Registration: Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824.
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http://dx.doi.org/10.1002/eat.23192DOI Listing
February 2020

Patterns of Opioid and Benzodiazepine Use in Opioid-Naïve Patients with Newly Diagnosed Low Back and Lower Extremity Pain.

J Gen Intern Med 2020 01 12;35(1):291-297. Epub 2019 Nov 12.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.

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 < 0.001); however, prescribing of benzodiazepines only decreased from 11.6% in 2008 to 10.8% in 2015. Patients with continued or new benzodiazepine use consistently used more opioids than patients who never used or stopped using benzodiazepines during the study period (one-way ANOVA, P < 0.001). For patients with continued and new benzodiazepine use, the odds ratio of long-term opioid use compared with those never prescribed a benzodiazepine was 2.99 (95% CI, 2.89-3.08) and 2.68 (95% CI, 2.62-2.75), respectively.

Limitations: This study used administrative claims analyses, which rely on accuracy and completeness of diagnostic, procedural, and prescription codes.

Conclusion: Overall opioid prescribing for low back pain or lower extremity pain decreased substantially during the study period, indicating a shift in management within the medical community. Rates of benzodiazepine prescribing, however, remained at approximately 11%. Concurrent prescriptions of benzodiazepines and opioids after LBP or LEP diagnosis were associated with increased risk of long-term opioid use.
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http://dx.doi.org/10.1007/s11606-019-05549-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957597PMC
January 2020

Atrial Fibrillation Burden Signature and Near-Term Prediction of Stroke: A Machine Learning Analysis.

Circ Cardiovasc Qual Outcomes 2019 10 15;12(10):e005595. Epub 2019 Oct 15.

Veterans Affairs Palo Alto Health Care System, Palo Alto, CA (M.A., S.K.S., J.F., M.P.T.).

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 CHADS-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 CHADS-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 CHADS-VASc had an AUC of 0.5 or less in both data sets. Combining CHADS-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 CHADS-VASc for near-term risk of stroke.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.118.005595DOI Listing
October 2019

How are medical students using the Electronic Health Record (EHR)?: An analysis of EHR use on an inpatient medicine rotation.

PLoS One 2019 16;14(8):e0221300. Epub 2019 Aug 16.

Department of Internal Medicine, Division of Hospital Medicine, Stanford University School of Medicine, Stanford, California, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221300PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697335PMC
April 2020

Initiative for Prevention and Early Identification of Delirium in Medical-Surgical Units: Lessons Learned in the Past Five Years.

Am J Med 2019 12 20;132(12):1421-1430.e8. Epub 2019 Jun 20.

Department of Medicine, Stanford University School of Medicine, Stanford, Calif; Department of Quality, Patient Safety, and Clinical Effectiveness, Stanford, Calif.

Background: Delirium is an acute change in mental status affecting 10%-64% of hospitalized patients, and may be preventable in 30%-40% of cases. In October 2013, a task force for delirium prevention and early identification in medical-surgical units was formed at our hospital. We studied whether our standardized protocol prevented delirium among high-risk patients.

Methods: We studied 105,455 patient encounters between November 2013 and January 2018. Since November 2013, there has been ongoing education to decrease deliriogenic medications use. Since 2014, nurses screen all patients for presence or absence of delirium using the Confusion Assessment Method (CAM). Since 2015, nurses additionally screen all patients for risk of delirium. In 2015, a physician order set for delirium was created. Nonpharmacological measures are implemented for high-risk or CAM positive patients.

Results: 98.8% of patient encounters had CAM screening, and 99.6% had delirium risk screening. Since 2013, odds of opiate use decreased by 5.0% per year (P < .001), and odds of benzodiazepine use decreased by 8.0% per year (P < .001). There was no change in anticholinergic use. In the adjusted analysis, since 2015, odds of delirium decreased by 25.3% per year among high-risk patients (n = 21,465; P < .001). Among high-risk patients or those diagnosed with delirium (n = 22,121), estimated length of stay decreased by 0.13 days per year (P < .001), odds of inpatient mortality decreased by 16.0% per year (P = .011), and odds of discharge to a nursing home decreased by 17.1% per year (P < .001).

Conclusion: With high clinician engagement and simplified workflows, our delirium initiative has shown sustained results.
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http://dx.doi.org/10.1016/j.amjmed.2019.05.035DOI Listing
December 2019

Determinants of Cost Variation in Total Hip and Knee Arthroplasty: Implications for Alternative Payment Models.

J Am Acad Orthop Surg 2020 Mar;28(6):e245-e254

From the Department of Medicine (Dr. Rudy, Dr. Ahuja, and Dr. Rohatgi), Stanford University School of Medicine, and the Quantitative Science Unit (Dr. Bentley), Stanford University, Stanford, CA.

Background: Alternative payment models have been proposed to deliver high-quality, cost-effective care. Under these models, payments may be shared between the hospital and the post-acute care services. Post-acute care services may account for one-third of the episode costs for total hip or knee arthroplasty (THA/TKA). Because hospitals or episode initiators bear notable financial risks in these payment models with minimal risk adjustment for complexity, it has been suggested these models may lead to prospective selection of healthier and younger patients. Studies evaluating the effect of patient demographics, medical complexity, and surgical characteristics on the cost of index hospitalization have been limited. We aimed to (1) quantify the impact of patient demographics, medical complexity, and surgical characteristics (type of anesthesia and operating time) on variation in direct cost of index hospitalization and (2) examine the association of these characteristics with discharge with home health services or to rehabilitation facility.

Methods: Retrospective study of 3,542 patients admitted to our hospital for elective THA/TKA between 2012 and 2017. Multivariable generalized estimating equations were used for analysis.

Results: Patient demographics and medical complexity accounted for 6.2% (THA) and 5.6% (TKA) of variation in direct cost of index hospitalization. Surgical characteristics accounted for 37.1% (THA) and 35.3% (TKA) of the cost variation. One thousand one hundred eighty-three (53.4%) patients were discharged with home health services, and 1,237 (29.4%) were discharged to rehabilitation facility. Patient demographics and higher medical complexity were markedly associated with discharge with home health services or to rehabilitation facility after THA/TKA.

Discussion: Patient demographics and medical complexity had minimal impact on variation in direct cost of index hospitalization for elective THA/TKA compared with surgical characteristics but were markedly associated with discharge with home health services or to rehabilitation facility. Having additional risk adjustment in these payment models could mitigate concerns about access to care for higher risk, higher cost patients.
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http://dx.doi.org/10.5435/JAAOS-D-18-00718DOI Listing
March 2020

Expenditures and Health Care Utilization Among Adults With Newly Diagnosed Low Back and Lower Extremity Pain.

JAMA Netw Open 2019 05 3;2(5):e193676. Epub 2019 May 3.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California.

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.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.3676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512284PMC
May 2019

United States State-Level Variation in the Use of Neuraxial Analgesia During Labor for Pregnant Women.

JAMA Netw Open 2018 12 7;1(8):e186567. Epub 2018 Dec 7.

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California.

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.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.6567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324365PMC
December 2018

The impact of state parity laws on copayments for and adherence to oral endocrine therapy for breast cancer.

Cancer 2019 02 19;125(3):374-381. Epub 2018 Dec 19.

Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California.

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.
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http://dx.doi.org/10.1002/cncr.31910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340721PMC
February 2019

Association of Opioid Prescriptions From Dental Clinicians for US Adolescents and Young Adults With Subsequent Opioid Use and Abuse.

JAMA Intern Med 2019 02;179(2):145-152

Division of Gastroenterology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California.

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.
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http://dx.doi.org/10.1001/jamainternmed.2018.5419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439650PMC
February 2019

Reply to Ritchie-McLean, Susanna; Wilmshurst, Sally, regarding their comment "Can population cohort studies assess the long-term impact of anesthesia in children?"

Paediatr Anaesth 2018 12;28(12):1157-1158

Child Population and Translational Health Research, The Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1111/pan.13520DOI Listing
December 2018

An Electronic Best Practice Alert Based on Choosing Wisely Guidelines Reduces Thrombophilia Testing in the Outpatient Setting.

J Gen Intern Med 2019 01;34(1):29-30

Department of Medicine, Division of Hospital Medicine, Stanford University School of Medicine, 300 Pasteur Drive, HC007, Stanford, CA, 94305, USA.

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http://dx.doi.org/10.1007/s11606-018-4663-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318198PMC
January 2019

Initial Provider Specialty Is Associated With Long-term Opiate Use in Patients With Newly Diagnosed Low Back and Lower Extremity Pain.

Spine (Phila Pa 1976) 2019 Feb;44(3):211-218

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA.

Study Design: Retrospective longitudinal cohort analysis of patients diagnosed in 2010, with continuous enrollment 6 months prior to and 12 months following the initial visit.

Objective: To determine whether provider specialty influences patterns of opiate utilization long after initial diagnosis.

Summary Of Background Data: Patients with low back pain present to a variety of providers and receive a spectrum of treatments, including opiate medications. The impact of initial provider type on opiate use in this population is uncertain.

Methods: We performed a retrospective analysis of opiate-naïve adult patients in the United States with newly diagnosed low back or lower extremity pain. We estimated the risk of early opiate prescription (≤14 d from diagnosis) and long-term opiate use (≥six prescriptions in 12 mo) based on the provider type at initial diagnosis using multivariable logistic regression, adjusting for patient demographics and comorbidities.

Results: We identified 478,981 newly diagnosed opiate-naïve patients. Of these, 40.4% received an opiate prescription within 1 year and 4.0% met criteria for long-term use. The most common initial provider type was family practice, associated with a 24.4% risk of early opiate prescription (95% CI, 24.1-24.6) and a 2.0% risk of long-term opiate use (95% CI, 2.0-2.1). Risk of receiving an early opiate prescription was higher among patients initially diagnosed by emergency medicine (43.1%; 95% CI, 41.6-44.5) or at an urgent care facility (40.8%; 95% CI, 39.4-42.3). Risk of long-term opiate use was highest for patients initially diagnosed by pain management/anesthesia (6.7%; 95% CI, 6.0-7.3) or physical medicine and rehabilitation (3.4%; 95% CI, 3.1-3.8) providers.

Conclusion: Initial provider type influences early opiate prescription and long-term opiate use among opiate-naïve patients with newly diagnosed low back and lower extremity pain.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000002840DOI Listing
February 2019

A population-based comparison of the post-operative outcomes of open and laparoscopic appendicectomy in children.

Med J Aust 2018 07 9;209(2):80-85. Epub 2018 Jul 9.

Menzies Centre for Health Policy, University of Sydney, Sydney, NSW.

Objective: To assess and compare the post-operative outcomes of open and laparoscopic appendicectomy in children.

Design: Record linkage analysis of administrative hospital (Admitted Patient Data Collection) and emergency department (Emergency Department Data Collection) data.Participants, setting: Children under 16 years of age who underwent an appendicectomy in a public or private hospital in New South Wales between January 2002 and December 2013.

Main Outcome Measures: Association between type of appendicectomy and post-operative complications within 28 days of discharge, adjusted for patient characteristics and type of hospital.

Results: Of 23 961 children who underwent appendicectomy, 19 336 (81%) had uncomplicated appendicitis and 4625 (19%) had appendicitis complicated by abscess, perforation, or peritonitis. The proportion of laparoscopic appendicectomies increased from 11.8% in 2002 to 85.8% in 2013. In cases of uncomplicated appendicitis, laparoscopic appendicectomy was associated with more post-operative complications (mostly symptomatic re-admissions or emergency department presentations) than open appendicectomy (7.4% v 5.8%), but with a reduced risk of post-operative intestinal obstruction (adjusted odds ratio [aOR], 0.59; 95% CI, 0.36-0.97). For cases of complicated appendicitis, the risk of wound infections was lower for laparoscopic appendicectomy (aOR, 0.67; 95% CI, 0.50-0.90), but not the risks of intestinal obstruction (aOR, 0.97; 95% CI, 0.62-1.52) or intra-abdominal abscess (aOR, 1.06; 95% CI, 0.72-1.55).

Conclusion: Post-appendicectomy outcomes were similar for most age groups and hospital types. Children with uncomplicated appendicitis have lower risk of post-operative bowel obstruction after laparoscopic appendicectomy than after open appendicectomy, but may be discharged before their post-operative symptoms have adequately resolved.
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http://dx.doi.org/10.5694/mja17.00541DOI Listing
July 2018

Gestation at birth, mode of birth, infant feeding and childhood hospitalization with infection.

Acta Obstet Gynecol Scand 2018 Aug 29;97(8):988-997. Epub 2018 May 29.

Menzies Center for Health Policy, School of Public Health, University of Sydney, Sydney, New South Wales, Australia.

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 <39 weeks and formula feeding increase the risk of infection-related hospitalization in childhood, which increases further when these factors co-occur. Reducing early planned birth and supporting breastfeeding are potentially cost-effective approaches to reducing the risk of hospitalization.
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http://dx.doi.org/10.1111/aogs.13371DOI Listing
August 2018