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The federal Employee Retirement Income Security Act of 1974 (ERISA) supersedes state laws as they relate to employer-based health care plans. Thus, cases brought under ERISA are heard in federal courts. We examined the intent, scope, and impact of recent laws passed in 10 states attempting to expand the legal rights of health plan enrollees to sue their plans. In June 2004, the US Supreme Court ruled that state-law causes of action brought under the Texas Health Care Liability Act involving coverage decisions by Aetna Health Inc and CIGNA Health Care of Texas were preempted by ERISA. The full implications of this decision are not evident at present. [ABSTRACT FROM AUTHOR]

Background: A growing line of research indicates a positive relationship between a healthcare organization's culture and various performance measures. In these studies, a key cultural characteristic is the emphasis placed on teamwork. None of the studies, however, have examined teamwork culture relative to patient satisfaction, which is now 1 of the most widely used performance measures for healthcare organizations.Objectives: This study investigated the relationship between teamwork culture of hospitals and patient reports of their satisfaction with the care they received.Methods: The study setting was the Veterans Health Administration (VHA), Department of Veterans Affairs. The study sample consisted of 125 VHA hospitals for which independent and valid sources of data for culture and patient satisfaction were obtained. Each hospital's culture was assessed relative to 4 dimensions: teamwork, entrepreneurial, bureaucratic, and rational. Patient satisfaction data were available for both inpatient and outpatient settings.Results: Results from multivariate regression analyses indicated a significant and positive relation between teamwork culture and patient satisfaction for inpatient care, and a significant and negative relation between bureaucratic culture and patient satisfaction for inpatient care. Additional analyses revealed an almost 1 standard deviation difference in patient satisfaction scores between hospitals in the top third and bottom third of the distribution for the teamwork culture measure.Conclusion: Study results suggest that hospitals and possibly other healthcare organizations should strive to develop a culture emphasizing teamwork and deemphasizing those aspects of bureaucracy that are not essential to assuring efficiency and quality care. [ABSTRACT FROM AUTHOR]

Background: Opioid use disorder (OUD) remains a significant public health issue as the number of opioid-related overdose deaths continues to reach new highs each year. Buprenorphine/Naloxone is a medication that has been shown to be highly effective for the treatment of OUD. However, the clinical management of patients on this medication is challenging as many patients discontinue treatment prematurely. We conducted a qualitative study focusing on experienced prescribers of buprenorphine to learn about what they believe are key challenges in prescribing this medication to patients with OUD and related strategies for improving treatment outcomes., Methods: We conducted two rounds of interviews with 12 prescribers who were either trained as a primary care physician, nurse practitioner, or physician assistant. These prescribers were recruited from an academically-based treatment program, a community health center, and a commercial substance use disorder treatment facility. Interview data were coded and analyzed in accordance with a grounded theory approach., Results: Key findings and related recommendations emerged for patient monitoring, integration of behavioral health with prescribing, patient volume requirements, and use of telehealth., Conclusion: The interviews generated a number of recommendations for improving patient outcomes from buprenorphine treatment. Some of these recommendations can be implemented quite readily whereas others entail more substantial resources and time commitments., Competing Interests: Declarations. Ethics approval and consent to participate: Approval was secured from a Northeastern University Institutional Review Board (IRB 19-05-06) and consent was obtained from all study participants. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Objectives: This study investigates the impact of participation in self-help groups on treatment completion among individuals undergoing medication for opioid use disorder (MOUD) treatment. Given the suboptimal adherence and retention rates for MOUD, this research seeks to examine the association between treatment completion and patient-level factors. Specifically, we evaluated the causal relationship between self-help group participation and treatment completion for patients undergoing MOUD., Methods: We used the Substance Abuse and Mental Health Services Administration's (SAMHSA) Treatment Episode Data Set: Discharges (TEDS-D) from 2015 to 2019. The data are filtered by the patient's opioid use history, demographics, treatment modality, and other relevant information. In this observational study, machine learning models (Lasso Regression, Decision Trees, Random Forest, and XGBoost) were developed to predict treatment completion. Outcome Adaptive Elastic Net (OAENet) was used to select confounders and outcome predictors, and the robust McNemars test was used to evaluate the causal relationship between self-help group participation and MOUD treatment completion., Results: The machine-learning models showed a strong association between participation in self-help groups and treatment completion. Our causal analysis demonstrated an average treatment effect on treated (ATT) of 0.260 and a p-value < 0.0001 for the robust McNemars test., Conclusions: Our study demonstrates the importance of participation in self-help groups for MOUD treatment recipients. We found that participation in MOUD along with self-help groups caused higher chances of treatment completion than MOUD alone. This suggests that policymakers should consider further integrating self-help groups into the treatment for OUD to improve the adherence and completion rate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Clinical uncertainty in primary care regarding the prognosis of children with respiratory tract infections contributes to the unnecessary use of antibiotics. Improved identification of children at low risk of future hospitalisation might reduce clinical uncertainty. A National Institute for Health and Care Research-funded 5-year programme (RP-PG-0608-10018) was used to develop and feasibility test an intervention., Objectives: The aim of the children with acute cough randomised controlled trial was to reduce antibiotic prescribing among children presenting with acute cough and respiratory tract infection without increasing hospital admission., Design: An efficient, pragmatic open-label, two-arm trial (with embedded qualitative and health economic analyses) using practice-level randomisation using routinely collected data as the primary outcome., Setting: General practitioner practices in England., Participants: General practitioner practices using the Egton Medical Information Systems ® patient-record system for children aged 0-9 years presenting with a cough or upper respiratory tract infection. Recruited by Clinical Research Networks and Clinical Commissioning Groups., Intervention: Comprised: (1) elicitation of parental concerns during consultation; (2) a clinician-focused prognostic algorithm to identify children with acute cough and respiratory tract infection at low, average or elevated risk of hospitalisation in the next 30 days accompanied by prescribing guidance, (3) provision of a printout for carers including safety-netting advice., Main Outcome Measures: Co-primaries using the practice list-size for children aged 0-9 years as the denominator: rate of dispensed amoxicillin and macrolide items at each practice (superiority comparison) from NHS Business Services Authority ePACT2 and rate of hospital admission for respiratory tract infection (non-inferiority comparison) from Clinical Commissioning Groups, both routinely collected over 12 months., Results: Of the 310 practices required, 294 (95%) were recruited (144 intervention and 150 controls) with 336,496 registered 0-9-year-olds (5% of all 0-9-year-old children in England) from 47 Clinical Commissioning Groups. Included practices were slightly larger than those not included, had slightly lower baseline dispensing rates and were located in more deprived areas (reflecting the distribution for practice postcodes nationally). Twelve practices (4%) subsequently withdrew (six related to the pandemic). The median number of times the intervention was used was 70 per practice (by a median of 9 clinicians) over 12 months. There was no evidence that the antibiotic dispensing rate in the intervention practices [0.155 (95% confidence interval 0.135 to 0.179)] differed to controls [0.154 (95% confidence interval 0.130 to 0.182), relative risk= 1.011 (95% confidence interval 0.992 to 1.029); p = 0.253]. There was, overall, a reduction in dispensing levels and intervention usage during the pandemic. The rate of hospitalisation for respiratory tract infection in the intervention practices [0.019 (95% confidence interval 0.014 to 0.026)] compared to the controls [0.021 (95% confidence interval 0.014 to 0.029)] was non-inferior [relative risk = 0.952 (95% confidence interval 0.905 to 1.003)]. The qualitative evaluation found the clinicians liked the intervention, used it as a supportive aid, especially with borderline cases but that it, did not always integrate well within the consultation flow and was used less over time. The economic evaluation found no evidence of a difference in mean National Health Service costs between arms; mean difference -£1999 (95% confidence interval -£6627 to 2630)., Conclusions: The intervention was feasible and subjectively useful to practitioners, with no evidence of harm in terms of hospitalisations, but did not impact on antibiotic prescribing rates., Future Work and Limitations: Although the intervention does not appear to change prescribing behaviour, elements of the approach may be used in the design of future interventions., Trial Registration: This trial is registered as ISRCTN11405239 (date assigned 20 April 2018) at www.controlled-trials.com (accessed 5 September 2022). Version 4.0 of the protocol is available at: https://www.journalslibrary.nihr.ac.uk/ (accessed 5 September 2022)., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (NIHR award ref: 16/31/98) programme and is published in full in Health Technology Assessment ; Vol. 27, No. 32. See the NIHR Funding and Awards website for further award information.

Using hospital cost report data from the Centers for Medicare and Medicaid Services, we examined the changes in hospitals' operating margins and total margins between 2019 and 2021. We found that, as of 2021, hospitals' operating margins had not fully rebounded to 2019 levels, although they had recovered from the 2020 nadirs. Conversely, average total margins increased by 140% during this period across all US hospitals, with the most significant growth occurring among rural hospitals, publicly operated hospitals, and critical access hospitals. Rural hospitals exhibited the largest gains in total margins during this time, experiencing a 1600% increase from 2019 to 2021. Our findings indicate that government relief funding tied to the COVID-19 Public Health Emergency significantly bolstered the financial health of the average hospital and had an outsize effect on lifting total margins among smaller hospitals that entered the pandemic in the most financially vulnerable position., Competing Interests: Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2023. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

Background: Buprenorphine is a widely used treatment option for patients with opioid use disorder (OUD). Premature discontinuation from this treatment has many negative health and societal consequences., Objective: To develop and evaluate a machine learning based two-stage clinical decision-making framework for predicting which patients will discontinue OUD treatment within less than a year. The proposed framework performs such prediction in two stages: (i) at the time of initiating the treatment, and (ii) after two/three months following treatment initiation., Methods: For this retrospective observational analysis, we utilized Massachusetts All Payer Claims Data (MA APCD) from the year 2013 to 2015. Study sample included 5190 patients who were commercially insured, initiated buprenorphine treatment between January and December 2014, and did not have any buprenorphine prescription at least one year prior to the date of treatment initiation in 2014. Treatment discontinuation was defined as at least two consecutive months without a prescription for buprenorphine. Six machine learning models (i.e., logistic regression, decision tree, random forest, extreme-gradient boosting, support vector machine, and artificial neural network) were tested using a five-fold cross validation on the input data. The first-stage models used patients' demographic information. The second-stage models included information on medication adherence during the early phase of treatment based on the proportion of days covered (PDC) measure., Results: A substantial percentage of patients (48.7%) who started on buprenorphine discontinued the treatment within one year. The area under receiving operating characteristic curve (C-statistic) for the first stage models varied within a range of 0.55 to 0.59. The inclusion of knowledge regarding patients' adherence at the early treatment phase in terms of two-months and three-months PDC resulted in a statistically significant increase in the models' discriminative power (p-value < 0.001) based on the C-statistic. We also constructed interpretable decision classification rules using the decision tree model., Conclusion: Machine learning models can predict which patients are most at-risk of premature treatment discontinuation with reasonable discriminative power. The proposed machine learning framework can be used as a tool to help inform a clinical decision support system following further validation. This can potentially help prescribers allocate limited healthcare resources optimally among different groups of patients based on their vulnerability to treatment discontinuation and design personalized support systems for improving patients' long-term adherence to OUD treatment., (© 2021. The Author(s).)

Background: The Patient Protection and Affordable Care Act of 2010 (ACA) encouraged nonprofit hospitals to collaborate with local public health experts in the conduct of community health needs assessments (CHNAs) for the larger goal of improving community health. Yet, little is known about whether collaborations between local health departments and hospitals may be beneficial to community health. In this study, we investigated whether individuals residing in communities with stronger collaboration between nonprofit hospitals and local public health departments (LHDs) reported healthier behaviors. We further explored whether social capital acts as a moderating factor of these relationships., Methods: We used multilevel cross-sectional models, controlling for both individual and community-level factors to explore LHD-hospital collaboration (measured in the National Association of County and City Health Officials (NACCHO) Forces of Change Survey), in relation to individual-level health behaviors in 56,826 adults living in 32 metropolitan and micropolitan statistical areas, captured through the 2015 Behavioral Risk Factor Surveillance System (BRFSS) SMART dataset. Nine health behaviors were examined including vigorous exercise, eating fruits and vegetables, smoking and binge drinking. Social capital, measured using an index developed by the Northeast Regional Center for Rural Development, was also explored as an effect modifier of these relationships., Results: Stronger collaboration between nonprofit hospitals and LHDs was associated with not smoking (odds ratio, OR 1.32, 95% CI 1.11 to 1.58), eating vegetables daily (OR 1.29; 95% CI 1.06 to 1.57), and vigorous exercise (OR 1.17; 95% CI 1.05 to 1.30). The presence of higher social capital also strengthened the relationships between LHD-hospital collaborations and wearing a seatbelt (p for interaction = 0.01) and general exercise (p for interaction = 0.03)., Conclusions: Stronger collaboration between nonprofit hospitals and LHDs was positively associated with healthier individual-level behaviors. Social capital may also play a moderating role in improving individual and population health.

Background: Acute lower respiratory tract infection (ALRTI) is often treated in primary care with antibiotics. The recent Oral Steroids for Acute Cough (OSAC) randomised controlled trial (RCT) showed corticosteroids were not an effective alternative in adults without a diagnosis of asthma with ALRTI., Aim: To investigate if corticosteroids are beneficial for ALRTI in patients with unrecognised asthma., Design & Setting: An exploratory analysis was undertaken of the primary care OSAC trial., Method: A subgroup analysis was performed in patients who responded 'yes' to the following International Primary Care Airways Group (IPCAG) question: did you have wheeze and/or at least two of nocturnal cough or chest tightness or dyspnoea in the past year. Sensitivity analyses were carried out on those who answered 'yes' to wheeze and at least two of the nocturnal symptoms. The primary outcomes were as follows: duration of cough (0-28 days, minimum clinically important difference [MCID] of 3.79 days) and mean symptom severity score (range 0-6; MCID 1.66 units)., Results: In total, 40 (10%) patients were included in the main analysis: mean age 49 years (standard deviation [SD] = 17.9), 52% male. Median cough duration was 3 days in both prednisolone (interquartile range [IQR] = 2-6 days) and placebo (IQR = 1-6 days) groups (adjusted hazard ratio [HR] = 1.10; 95% confidence interval [CI] = 0.47 to 2.54; P = 0.83), equating to 0.24 days longer in the prednisolone group (95% CI = 1.23 days shorter to 2.88 days longer). Mean symptom severity difference was -0.14 (95% CI = -0.78 to 0.49; P =0.65) comparing prednisolone with placebo. Similar findings were found in the sensitivity analysis., Conclusion: No evidence was found to support the use of corticosteroids for ALRTI in patients with clinically unrecognised asthma. Clinicians should not use the IPCAG questions to target oral corticosteroid treatment in patients with ALRTI., (Copyright © 2020, The Authors.)

Objectives: To evaluate the association between regional market factors and experience with patient-provider communication in primary care services of safety net hospitals., Study Design: A retrospective cohort study with 933,407 patient experience survey respondents from 128 Veterans Health Administration (VHA) hospitals between fiscal years 2013 and 2016., Methods: Patient responses on 5 patient-provider communication questions were used to evaluate quality of care. Six regional market factors were used to characterize veterans' health care insurance coverage and affluence. A logistic regression was used to examine changes in individual-level patient-provider communication experience when regional market factors increase or decrease the demand for VHA primary care services., Results: Our findings supported our hypothesis that changes in regional market factors shift patient demand for VHA care and affect patient-provider communication measured by patient experience surveys. The adjusted odds ratio (AOR) of positive patient-provider communication was associated with a regional increase (first to third quartile) of employer-sponsored insurance (AOR, 1.028; 95% CI, 1.001-1.055) and a decrease (third to first quartile) in the veterans' unemployment rate (AOR, 0.966; 95% CI, 0.944-0.990). Higher primary care capacity (first to third quartile) was also associated with positive patient-provider communication (AOR, 1.050; 95% CI, 1.018-1.082)., Conclusions: Findings from this study raise concerns that safety net hospitals could be unfairly penalized by value-based payment programs and Medicare Hospital Compare. Such policies and programs could improve resource allocation by accounting for regional market factors before acting on quality of care measures.

Background: Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery., Objectives: The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome., Design: This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research., Setting: Urology departments of 26 NHS hospitals in England., Participants: Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised., Interventions: Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm)., Main Outcome Measures: The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness., Results: A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (-0.33, 95% CI -1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43-44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS., Limitations: The trial met its predefined recruitment target, but surgery rates were lower than anticipated., Conclusions: Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS., Future Work: Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy., Trial Registration: Current Controlled Trials ISRCTN56164274., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 42. See the NIHR Journals Library website for further project information., Competing Interests: Outside this work, Paul Abrams reports grants and personal fees for being a consultant and speaker for Astellas Pharma Inc. (Tokyo, Japan), and personal fees for being a consultant for Ipsen (Paris, France) and a speaker for Pfizer Inc. (New York City, NY, USA) and Sun Pharmaceutical Industries Ltd (Mumbai, India). He also reports personal fees from Pierre Fabre S.A. (Paris, France) and Coloplast Ltd (Peterborough, UK). Christopher Chapple reports being an author for Allergan plc (Dublin, Ireland) and Astellas Pharma; being an investigator for scientific studies/trials with Astellas Pharma and Ipsen; being a patent holder with Symimetics; receiving personal fees as a consultant/advisor for Astellas Pharma, Bayer Schering Pharma GmbH (Berlin, Germany), Ferring Pharmaceuticals (Saint-Prex, Switzerland), Galvani Bioelectronics (GlaxoSmithKline; Stevenage, UK), Pierre Fabre, Symimetics, TARIS Biomedical Inc. (Lexington, MA, USA), and Urovant Sciences (Irvine, CA, USA); and receiving personal fees as a meeting participant/speaker for Astellas Pharma and Pfizer. J Athene Lane was a member of the Clinical Trials Unit funded by the National Institute for Health Research during the conduct of this trial. Marcus J Drake reports being on associated advisory boards and has received grants, personal fees and non-financial support from Allergan, Astellas Pharma and Ferring Pharmaceuticals. He has also received personal fees from Pfizer.

Background: Although previous research has demonstrated high rates of inappropriate diagnostic imaging, the potential influence of several physician-level characteristics is not well established., Objective: To examine the influence of three types of physician characteristics on inappropriate imaging: experience, specialty training, and self-referral., Design: A retrospective analysis of over 70,000 MRI claims submitted for commercially insured individuals. Physician characteristics were identified through a combination of administrative records and primary data collection. Multi-level modeling was used to assess relationships between physician characteristics and inappropriate MRIs., Setting: Massachusetts PARTICIPANTS: Commercially insured individuals who received an MRI between 2010 and 2013 for one of three conditions: low back pain, knee pain, and shoulder pain., Measurements: Guidelines from the American College of Radiology were used to classify MRI referrals as appropriate/inappropriate. Experience was measured from the date of medical school graduation. Specialty training comprised three principal groups: general internal medicine, family medicine, and orthopedics. Two forms of self-referral were examined: (a) the same physician who ordered the procedure also performed it, and (b) the physicians who ordered and performed the procedure were members of the same group practice and the procedure was performed outside the hospital setting., Results: Approximately 23% of claims were classified as inappropriate. Physicians with 10 or less years of experience had significantly higher odds of ordering inappropriate MRIs. Primary care physicians were almost twice as likely to order an inappropriate MRI as orthopedists. Self-referral was not associated with higher rates of inappropriate MRIs., Limitations: Classification of MRIs was conducted with claims data. Not all self-referred MRIs could be detected., Conclusions: Inappropriate imaging continues to be a driver of wasteful health care spending. Both physician experience and specialty training were highly associated with inappropriate imaging.

Objective: To quantify the level of adherence to imaging guidelines for three common clinical indications for a commercially insured population., Design: Retrospective analysis of administrative claims data for commercially insured individuals with diagnostic imaging claims (MRI and X-ray) for either uncomplicated low back pain, non-traumatic knee pain or non-traumatic shoulder pain., Setting: The State of Massachusetts for 2010 and 2013., Participants: Adults with no chronic conditions and without evidence of prior management in the 12 months preceding to the initial office visit for each of the clinical indications., Main Outcomes Measures: Imaging procedures performed within 30 days of the initial office visit were classified as appropriate or inappropriate according to adherence to imaging guidelines from American College of Radiology., Results: More than 60% of lumbar spine MRI's were deemed inappropriate in 2010 and in 2013. Over 30% of MRI's for shoulder pain and knee pain were inappropriate in 2010 and in 2013. Patients age 18-59 with inappropriate imaging claims had significantly lower rates of surgical procedures within 90 days of imaging than those with appropriate imaging. Inappropriate imaging accounted for over 20% of annual imaging costs for the three clinical indications., Conclusions: Reducing inappropriate imaging procedures can lead to substantial savings through the elimination of unnecessary and low value procedures. Increased awareness of and adherence to best practice guidelines should be a focus of efforts to cut waste in our healthcare system., (© The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Under the current policy decision making paradigm we make or evaluate a policy decision by intervening different socio-economic parameters and analyzing the impact of those interventions. This process involves identifying the causal relation between interventions and outcomes. Matching method is one of the popular techniques to identify such causal relations. However, in one-to-one matching, when a treatment or control unit has multiple pair assignment options with similar match quality, different matching algorithms often assign different pairs. Since all the matching algorithms assign pairs without considering the outcomes, it is possible that with the same data and same hypothesis, different experimenters can reach different conclusions creating an uncertainty in policy decision making. This problem becomes more prominent in the case of large-scale observational studies as there are more pair assignment options. Recently, a robust approach has been proposed to tackle the uncertainty that uses an integer programming model to explore all possible assignments. Though the proposed integer programming model is very efficient in making robust causal inference, it is not scalable to big data observational studies. With the current approach, an observational study with 50,000 samples will generate hundreds of thousands binary variables. Solving such integer programming problem is computationally expensive and becomes even worse with the increase of sample size. In this work, we consider causal inference testing with binary outcomes and propose computationally efficient algorithms that are adaptable for large-scale observational studies. By leveraging the structure of the optimization model, we propose a robustness condition that further reduces the computational burden. We validate the efficiency of the proposed algorithms by testing the causal relation between the Medicare Hospital Readmission Reduction Program (HRRP) and non-index readmissions (i.e., readmission to a hospital that is different from the hospital that discharged the patient) from the State of California Patient Discharge Database from 2010 to 2014. Our result shows that HRRP has a causal relation with the increase in non-index readmissions. The proposed algorithms proved to be highly scalable in testing causal relations from large-scale observational studies., Competing Interests: The authors have declared that no competing interests exist.

Background: Acute otitis media (AOM) is a common reason for primary care consultations and antibiotic prescribing in children. Options for improved pain control may influence antibiotic prescribing and consumption., Objective: The Children's Ear Pain Study (CEDAR) investigated whether or not providing anaesthetic-analgesic ear drops reduced antibiotic consumption in children with AOM. Secondary objectives included pain control and cost-effectiveness., Design: A multicentre, randomised, parallel-group (two-group initially, then three-group) trial., Setting: Primary care practices in England and Wales., Participants: 1- to 10-year-old children presenting within 1 week of suspected AOM onset with ear pain during the preceding 24 hours and not requiring immediate antibiotics. Participating children were logged into the study and allocated using a remote randomisation service., Interventions: Two-group trial - unblinded comparison of anaesthetic-analgesic ear drops versus usual care. Three-group trial - blinded comparison of anaesthetic-analgesic ear drops versus placebo ear drops and unblinded comparison with usual care., Main Outcome Measures: The primary outcome measure was parent-reported antibiotic use by the child over 8 days following enrolment. Secondary measures included ear pain at day 2 and NHS and societal costs over 8 days., Results: Owing to a delay in provision of the placebo drops, the recruitment period was shortened and most participants were randomly allocated to the two-group study ( n  = 74) rather than the three-group study ( n  = 32). Comparing active drops with usual care in the combined two-group and three-group studies, 1 out of 39 (3%) children allocated to the active drops group and 11 out of 38 (29%) children allocated to the usual-care group consumed antibiotics in the 8 days following enrolment [unadjusted odds ratio 0.09, 95% confidence interval (CI) 0.02 to 0.55; p  = 0.009; adjusted for delayed prescribing odds ratio 0.15, 95% CI 0.03 to 0.87; p  = 0.035]. A total of 43% (3/7) of patients in the placebo drops group consumed antibiotics by day 8, compared with 0% (0/10) of the three-group study active drops groups ( p  = 0.051). The economic analysis of NHS costs (£12.66 for active drops and £11.36 for usual care) leads to an estimated cost of £5.19 per antibiotic prescription avoided, but with a high degree of uncertainty. A reduction in ear pain at day 2 in the placebo group ( n  = 7) compared with the active drops group ( n  = 10) (adjusted difference in means 0.67, 95% CI -1.44 to 2.79; p  = 0.51) is consistent with chance. No adverse events were reported in children receiving active drops., Limitations: Estimated treatment effects are imprecise because the sample size target was not met. It is not clear if delayed prescriptions of an antibiotic were written prior to randomisation. Few children received placebo drops, which hindered the investigation of ear pain., Conclusions: This study suggests that reduced antibiotic use can be achieved in children with AOM by combining a no or delayed antibiotic prescribing strategy with anaesthetic-analgesic ear drops. Whether or not the active drops relieved ear pain was not established., Future Work: The observed reduction in antibiotic consumption following the prescription of ear drops requires replication in a larger study. Future work should establish if the effect of ear drops is due to pain relief., Trial Registration: Current Controlled Trials ISRCTN09599764., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 34. See the NIHR Journals Library website for further project information. Alastair D Hay was funded by a NIHR Research Professorship (funding identifier NIHR-RP-02-12-012)., Competing Interests: Alastair D Hay and William Hollingworth are members of the Health Technology Assessment Clinical Trials Board. Chris Metcalfe is a member of a clinical trials unit in receipt of National Institute for Health Research (NIHR) support funding. Desmond Nunez is an author of a related Cochrane review protocol. Paul Little is the Director of the NIHR Programme Grants for Applied Research programme and a member of the NIHR Journals Library Board.

Background: The drainage, irrigation and fibrinolytic therapy (DRIFT) trial, conducted in 2003-6, showed a reduced rate of death or severe disability at 2 years in the DRIFT compared with the standard treatment group, among preterm infants with intraventricular haemorrhage (IVH) and post-haemorrhagic ventricular dilatation., Objectives: To compare cognitive function, visual and sensorimotor ability, emotional well-being, use of specialist health/rehabilitative and educational services, neuroimaging, and economic costs and benefits at school age., Design: Ten-year follow-up of a randomised controlled trial., Setting: Neonatal intensive care units (Bristol, Katowice, Glasgow and Bergen)., Participants: Fifty-two of the original 77 infants randomised., Interventions: DRIFT or standard therapy (cerebrospinal fluid tapping)., Main Outcome Measures: Primary - cognitive disability. Secondary - vision; sensorimotor disability; emotional/behavioural function; education; neurosurgical sequelae on magnetic resonance imaging; preference-based measures of health-related quality of life; costs of neonatal treatment and of subsequent health care in childhood; health and social care costs and impact on family at age 10 years; and a decision analysis model to estimate the cost-effectiveness of DRIFT compared with standard treatment up to the age of 18 years., Results: By 10 years of age, 12 children had died and 13 were either lost to follow-up or had declined to participate. A total of 52 children were assessed at 10 years of age (DRIFT, n  = 28; standard treatment, n  = 24). Imbalances in gender and birthweight favoured the standard treatment group. The unadjusted mean cognitive quotient (CQ) score was 69.3 points [standard deviation (SD) 30.1 points] in the DRIFT group compared with 53.7 points (SD 35.7 points) in the standard treatment group, a difference of 15.7 points, 95% confidence interval (CI) -2.9 to 34.2 points; p  = 0.096. After adjusting for the prespecified covariates (gender, birthweight and grade of IVH), this evidence strengthened: children who received DRIFT had a CQ advantage of 23.5 points ( p  = 0.009). The binary outcome, alive without severe cognitive disability, gave strong evidence that DRIFT improved cognition [unadjusted odds ratio (OR) 3.6 (95% CI 1.2 to 11.0; p  = 0.026) and adjusted OR 10.0 (95% CI 2.1 to 46.7; p  = 0.004)]; the number needed to treat was three. No significant differences were found in any secondary outcomes. There was weak evidence that DRIFT reduced special school attendance (adjusted OR 0.27, 95% CI 0.07 to 1.05; p  = 0.059). The neonatal stay (unadjusted mean difference £6556, 95% CI -£11,161 to £24,273) and subsequent hospital care (£3413, 95% CI -£12,408 to £19,234) costs were higher in the DRIFT arm, but the wide CIs included zero. The decision analysis model indicated that DRIFT has the potential to be cost-effective at 18 years of age. The incremental cost-effectiveness ratio (£15,621 per quality-adjusted life-year) was below the National Institute for Health and Care Excellence threshold. The cost-effectiveness results were sensitive to adjustment for birthweight and gender., Limitations: The main limitations are the sample size of the trial and that important characteristics were unbalanced at baseline and at the 10-year follow-up. Although the analyses conducted here were prespecified in the analysis plan, they had not been prespecified in the original trial registration., Conclusions: DRIFT improves cognitive function when taking into account birthweight, grade of IVH and gender. DRIFT is probably effective and, given the reduction in the need for special education, has the potential to be cost-effective as well. A future UK multicentre trial is required to assess efficacy and safety of DRIFT when delivered across multiple sites., Trial Registration: Current Controlled Trials ISRCTN80286058., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 4. See the NIHR Journals Library website for further project information. The DRIFT trial and 2-year follow-up was funded by Cerebra and the James and Grace Anderson Trust., Competing Interests: No competing interests were declared.

Background: Longitudinal clinical experiences are a common component of undergraduate medical curricula, yet these programs have not been systematically characterized in US medical schools., Objective: Our study sought to identify and characterize longitudinal clinical programs (LCPs) in US medical schools and measure associations between programs' structures and goals., Design: Using a mixed-methods approach, we conducted a secondary analysis of data from publicly available websites. We conducted a systematic keyword search of the websites of 137 LCME-accredited US medical schools to identify LCPs. We included programs with student-patient interactions of at least six months. We categorized programs using qualitative thematic analysis and compared associations between program structures and goals., Results: We identified 98 LCPs in 69 schools. Half (52.0%) of LCPs occurred during the core clinical year. Program structures included 'clinic attachments' (50.0%), 'longitudinal integrated clerkships' (26.5%), and 'patient attachments' (20.4%). We identified goals in 89 programs, including 'exposing students to specific topics, patient demographics, or practice settings' (78.7%); 'clinical or professional skill development' (65.2%); and 'understanding the patient experience' (19.1%). Patient attachments were associated with 'exposure to specific patient demographics' (P = .04) and 'understanding the patient experience' (P = .03). Pre-clinical programs were associated with clinical skills development (P = .01)., Conclusions: Our study identifies the scope and nature of LCPs in US medical schools. Understanding connections between educational structures and goals may guide program design and research investigations of educational processes and outcomes.

Variations in treatment modalities for skin growths contribute substantially to overall healthcare spending within dermatology. However, little is known regarding factors impacting patient decision-making when choosing a treatment modality. In this survey-based, cross-sectional study (n = 375, 81.9% response rate), we asked patients to rate the importance of different treatment parameters for a nonfacial skin growth, further classified into five domains: efficacy, appearance, financial impact, visit duration, and productivity. Although patients generally prioritized treatment efficacy when selecting a treatment modality, they emphasized different aspects of the treatment experience as a function of age, gender, race, insurance status, and history of malignancy. Patients over age 50 were less likely to consider treatment impact on finances as being "important", but more so efficacy and visit duration. Women were more likely to value efficacy and appearance. Patients without private insurance were more likely to cite efficacy and impact on productivity as being "important". While the underlying reasons for these variations differ across patients, these findings help explain variations in treatment selection among patients choosing between treatments for skin growths and may ultimately lead to improved shared decision-making.

Objective: To examine the relationship between nurse staffing patterns and patients' experience of care in hospitals with a particular focus on staffing flexibility., Data Sources/study Setting: The study sample comprised U.S. general hospitals between 2010 and 2012. Nurse staffing data came from the American Hospital Association Annual Survey, and patient experience data came from the Medicare Hospital Consumer Assessment of Healthcare Providers and Systems., Study Design: An observational research design was used entailing a pooled, cross-sectional data set. Regression models were estimated using generalized estimating equation (GEE) and hospital fixed effects. Nurse staffing patterns were assessed based on both levels (i.e., ratio of full-time equivalent nurses per 1,000 patient days) and composition (i.e., skill mix-percentage of registered nurses; staffing flexibility-percentage of part-time nurses)., Principal Findings: All three staffing variables were significantly associated with patient experience in the GEE analysis, but only staffing flexibility was significant in the fixed-effects analysis. A higher percentage of part-time nurses was positively associated with patient experience. Multiplicative and nonlinear effects for the staffing variables were also observed., Conclusions: Among three staffing variables, flexibility was found to be the most important relative to patient experience. Unobserved hospital characteristics appear to underlie patient experience as well as certain nurse staffing patterns., (© Health Research and Educational Trust.)

Objectives: Although most nonprofit hospitals are required to conduct periodic community health needs assessments (CHNAs), such assessments arguably are most critical for communities with substantial health needs. The objective of this study was to describe differences in progress in conducting CHNAs between hospitals located in communities with the greatest compared with the fewest health needs., Methods: We used data on CHNA activity from the 2013 tax filings of 1331 US hospitals combined with data on community health needs from the County Health Rankings. We used bivariate and multivariate analyses to examine differences in hospitals' progress in implementing comprehensive CHNAs using 4 activities: (1) strategies to address identified needs, (2) participation in developing community-wide plans, (3) including CHNA into a hospital's operational plan, and (4) developing a budget to address identified needs. We compared progress in communities with the greatest and the fewest health needs using a comprehensive indicator comprising a community's socioeconomic factors, health behaviors, access to medical care, and physical environment., Results: In 2013, nonprofit hospitals serving communities with the greatest health needs conducted an average of 2.5 of the 4 CHNA activities, whereas hospitals serving communities with the fewest health needs conducted an average of 2.7 activities. Multivariate analysis, however, showed a negative but not significant relationship between the magnitude of a community's health needs and a hospital's progress in implementing comprehensive CHNAs., Conclusions: Hospitals serving communities with the greatest health needs face high demand for free and reduced-cost care, which may limit their ability to invest more of their community benefit dollars in initiatives aimed at improving the health of the community.

Objectives: To investigate whether tax-exempt hospitals' investments in community health are associated with patterns of governmental public health spending focusing specifically on the relationship between hospitals' community benefit expenditures and the spending patterns of local health departments (LHDs)., Study Design: We combined data on tax-exempt hospitals' community benefit spending with data on spending by the corresponding LHD that served the county in which a hospital was located. Data were available for 2 years, 2009 and 2013. Generalized linear regressions were estimated with indicators of hospital community benefit spending as the dependent variable and LHD spending as the key independent variable., Principal Findings: Hospital community benefit spending was unrelated to how much local public health agencies spent, per capita, on public health in their communities., Conclusions: Patterns of local public health spending do not appear to impact the investments of tax-exempt hospitals in community health activities. Opportunities may, however, exist for a more active engagement between the public and private sector to ensure that the expenditures of all stakeholders involved in community health improvement efforts complement one another., (© Health Research and Educational Trust.)

Objectives: To compare the completeness and agreement of prostate cancer data recorded by the National Cancer Registration and Analysis Service (NCRAS) with research-level data specifically abstracted from medical records from the Cluster randomised triAl of prostate specific antigen (PSA) testing for Prostate cancer (CAP) trial., Design: Cross-sectional comparison study., Participants: We included 1356 men from the CAP trial cohort who were linked to the NCRAS registry., Primary and Secondary Outcome Measures: Completeness of prostate cancer data in NCRAS and CAP and agreement for tumour, node, metastases (TNM) stage (T1/T2; T3; T4/N1/M1) and Gleason grade (4-6; 7; 8-10), measured by differences in proportions and Cohen's kappa statistic. Data were also stratified by year and pre-2010 versus post-2010, when NCRAS reporting standards changed., Results: Compared with CAP, completeness was lower in NCRAS for Gleason grade (41.2% vs 76.7%, difference 35.5, 95% CI 32.1 to 39.0) and TNM stage (29.9% vs 67.6%, difference 37.6, 95% CI 34.1 to 41.1). NCRAS completeness for Gleason grade (pre-2010 vs post-2010 31.69% vs 64%; difference 32.31, 95% CI 26.76 to 37.87) and TNM stage (19.31% vs 55.50%; difference 36.19, 95% CI 30.72 to 41.67) improved over time. Agreement for Gleason grade was high (Cohen's kappa, κ=0.90, 95% CI 0.88 to 0.93), but lower for TNM stage (κ=0.41, 95% CI 0.37 to 0.51) overall. There was a trend towards improved agreement on Gleason grade, but not TNM stage, when comparing pre-2010 and post-2010 data., Conclusion: NCRAS case identification was very high; however, data on prostate cancer grade was less complete than CAP, and agreement for TNM stage was modest. Although the completeness of NCRAS data has improved since 2010, the higher completeness rate in CAP demonstrates that gains could potentially be achieved in routine registry data. This study's findings highlight a need for improved recording of stage and grade data in the source medical records., Competing Interests: Competing interests: RM,ET, JOD, and CM have received grants from Cancer Research UK in the previous three years., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa)., Setting, Participants and Outcome Measures: Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man's age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study., Results: The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45-49 years to 53.0% for men aged 65-69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively)., Conclusion: A high proportion of men aged 45-69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa., Trial Registration Number: ISRCTN20141297,NCT02044172., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Current management for men with lower urinary tract symptoms (LUTS) is a pathway that results in prostate surgery in a significant proportion. While helpful in relieving benign prostatic obstruction (BPO), surgery may be ineffective for men suffering from difficulties not relating to BPO. The UPSTREAM trial started recruitment in October 2014 with the aim of establishing whether a care pathway including urodynamics (a diagnostic tool for BPO and thus an indication of whether surgery is needed) is no worse for men, in terms of symptomatic outcome, than one without (routine care)., Methods/design: This analysis plan outlines the main outcomes of the study and specific design choices, such as non-inferiority margins. The trial is currently recruiting in 26 hospitals across the UK, randomising men to either urodynamics or routine care, with recruitment set to end on the 31 December 2016. All outcomes will be measured 18 months after randomisation to allow sufficient time for surgical procedures and recovery. The primary outcome is based on a non-inferiority design with a margin of 1 point on the International Prostate Symptom Score (IPSS) scale. The key secondary outcome for this trial is surgery rate per arm, which is estimated to be at least 18% lower in the urodynamics arm. Surgery rates, adverse events, flow rate, urinary symptoms and sexual symptoms are secondary outcomes to be assessed for superiority. This is an update to the UPSTREAM protocol, which has already been published in this journal., Discussion: This a priori statistical analysis plan aims to reduce reporting bias by allowing access to the trial's objectives and plans in advance of recruitment end. The results of the trial are expected to be published soon after the trial end date of 30 September 2018., Trial Registration: ISRCTN registry, ISRCTN56164274 . Registered on 8 April 2014.

The importance of 1,5-anhydroglucitol (1,5-AG) as an intermediate biomarker for diabetic pregnancy is multi-fold: (1) it serves as a reliable indicator of moderate-level glycemic control, especially during early gestation; (2) it has been associated with increased risk of diabetes, independent of HbA1c and fasting glucose; and (3) it is an independent risk factor for the development of eclampsia during pregnancy. However, the clinical use of this biomarker during pregnancy has been underutilized due to physiological changes in glomerular filtration rate, plasma volume, and other hemodynamic parameters which have been hypothesized to bias gestational serum 1,5-AG concentrations. Here, we develop an in-silico model of gestational 1,5-AG by combining pre-existing physiological data in the literature with a two-compartment mathematical model, building off of a previous kinetic model described by Stickle and Turk (1997) Am. J. Physiol., 273, E821. Our model quantitatively characterizes how renal and hemodynamic factors impact measured 1,5-AG during normal pregnancy and during pregnancy with gestational diabetes and diabetes mellitus. During both normal and diabetic pregnancy, we find that a simple two-compartment model of 1,5-AG kinetics, with all parameters but reabsorption fraction adjusted for time in pregnancy, efficiently models 1,5-AG kinetics throughout the first two trimesters. Allowing reabsorption fraction to decrease after 25 weeks permits parameters closer to expected physiological values during the last trimester. Our quantitative model of 1,5-AG confirms the involvement of hypothesized renal and hemodynamic mechanisms during pregnancy, clarifying the expected trends in 1,5-AG to aid clinical interpretation. Further research and data may elucidate biological changes during the third trimester that account for the drop in 1,5-AG concentrations, and clarify physiological differences between diabetes subtypes during pregnancy., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Informed consent (IC) is an ethical and legal prerequisite for trial participation, yet current approaches evaluating participant understanding for IC during recruitment lack consistency. No validated measure has been identified that evaluates participant understanding for IC based on their contributions during consent interactions. This paper outlines the development and formative evaluation of the Participatory and Informed Consent (PIC) measure for application to recorded recruitment appointments. The PIC allows the evaluation of recruiter information provision and evidence of participant understanding., Methods: Published guidelines for IC were reviewed to identify potential items for inclusion. Seventeen purposively sampled trial recruitment appointments from three diverse trials were reviewed to identify the presence of items relevant to IC. A developmental version of the measure (DevPICv1) was drafted and applied to six further recruitment appointments from three further diverse trials to evaluate feasibility, validity, stability and inter-rater reliability. Findings guided revision of the measure (DevPICv2) which was applied to six further recruitment appointments as above., Results: DevPICv1 assessed recruiter information provision (detail and clarity assessed separately) and participant talk (detail and understanding assessed separately) over 20 parameters (or 23 parameters for three-arm trials). Initial application of the measure to six diverse recruitment appointments demonstrated promising stability and inter-rater reliability but a need to simplify the measure to shorten time for completion. The revised measure (DevPICv2) combined assessment of detail and clarity of recruiter information and detail and evidence of participant understanding into two single scales for application to 22 parameters or 25 parameters for three-arm trials. Application of DevPICv2 to six further diverse recruitment appointments showed considerable improvements in feasibility (e.g. time to complete) with good levels of stability (i.e. test-retest reliability) and inter-rater reliability maintained., Conclusions: The DevPICv2 provides a measure for application to trial recruitment appointments to evaluate quality of recruiter information provision and evidence of patient understanding and participation during IC discussions. Initial evaluation shows promising feasibility, validity, reliability and ability to discriminate across a range of recruiter practice and evidence of participant understanding. More validation work is needed in new clinical trials to evaluate and refine the measure further.

Melanoma is the most lethal of skin cancers, in part because of its proclivity for rapid and distant metastasis. It is also potentially the most neurotropic cancer in terms of probability of CNS metastasis from the primary lesion. Despite surgical resection and radiotherapy, prognosis remains guarded for patients with brain metastases. Over the past five years, a new domain of personalized therapy has emerged for advanced melanoma patients with the introduction of BRAF and other MAP kinase pathway inhibitors, immunotherapy, and combinatory therapeutic strategies. By targeting critical cellular signaling pathways and unleashing the adaptive immune response against tumor antigens, a subset of melanoma patients have demonstrated remarkable responses to these treatments. Over time, acquired resistance to these modalities inexorably develops, providing new challenges to overcome. We review the rapidly evolving terrain for intracranial melanoma treatment, address likely and potential mechanisms of resistance, as well as evaluate promising future therapeutic approaches currently under clinical investigation., Competing Interests: CONFLICTS OF INTEREST None.

Objectives: To identify how US tax-exempt hospitals are progressing in regard to community health needs assessment (CHNA) implementation following the Patient Protection and Affordable Care Act., Methods: We analyzed data on more than 1500 tax-exempt hospitals in 2013 to assess patterns in CHNA implementation and to determine whether a hospital's institutional and community characteristics are associated with greater progress., Results: Our findings show wide variation among hospitals in CHNA implementation. Hospitals operating as part of a health system as well as hospitals participating in a Medicare accountable care organization showed greater progress in CHNA implementation whereas hospitals serving a greater proportion of uninsured showed less progress. We also found that hospitals reporting the highest level of CHNA implementation progress spent more on community health improvement., Conclusions: Hospitals widely embraced the regulations to perform a CHNA. Less is known about how hospitals are moving forward to improve population health through the implementation of programs to meet identified community needs.

Mitochondrial genomes (mitogenomes) of flowering plants are well known for their extreme diversity in size, structure, gene content, and rates of sequence evolution and recombination. In contrast, little is known about mitogenomic diversity and evolution within gymnosperms. Only a single complete genome sequence is available, from the cycad Cycas taitungensis, while limited information is available for the one draft sequence, from Norway spruce (Picea abies). To examine mitogenomic evolution in gymnosperms, we generated complete genome sequences for the ginkgo tree (Ginkgo biloba) and a gnetophyte (Welwitschia mirabilis). There is great disparity in size, sequence conservation, levels of shared DNA, and functional content among gymnosperm mitogenomes. The Cycas and Ginkgo mitogenomes are relatively small, have low substitution rates, and possess numerous genes, introns, and edit sites; we infer that these properties were present in the ancestral seed plant. By contrast, the Welwitschia mitogenome has an expanded size coupled with accelerated substitution rates and extensive loss of these functional features. The Picea genome has expanded further, to more than 4 Mb. With regard to structural evolution, the Cycas and Ginkgo mitogenomes share a remarkable amount of intergenic DNA, which may be related to the limited recombinational activity detected at repeats in Ginkgo Conversely, the Welwitschia mitogenome shares almost no intergenic DNA with any other seed plant. By conducting the first measurements of rates of DNA turnover in seed plant mitogenomes, we discovered that turnover rates vary by orders of magnitude among species., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We examined the magnitude and related costs of potentially avoidable hospitalizations including re-hospitalizations for long-stay residents in nursing homes., Design: We conducted our investigation as a retrospective cohort study where the cohort comprised individuals who were eligible for Medicare and had spent at least 120 uninterrupted days in a nursing home in New York State between 2004 and 2007. To conduct the study, we linked the Minimum Data Set, Medicare Provider Assessment File and Provider of Service File., Measurements: We defined a potentially avoidable hospitalization as one where a resident was admitted to a hospital for which the principle diagnosis was 1 of 15 ambulatory care sensitive (ACS) conditions., Results: Although the percentage of total hospitalizations for ACS conditions declined during the study period, 20% or more of annual hospitalizations were for ACS conditions entailing Medicare payments in excess of $450 million. Approximately 40% of the residents who were hospitalized once for an ACS condition were re-hospitalized during the study period for the same or different ACS condition., Conclusion: During the study period, potentially avoidable hospitalizations from nursing homes were a common occurrence in New York. A substantial percentage of such hospitalizations involved residents who had been previously hospitalized, in some cases multiple times, for an ACS condition. Although the observed decline in ACS-related hospitalizations suggests improvements in nursing home care, various policy and managerial-level initiatives may be needed to ensure that nursing home residents are not exposed to a substantial risk of avoidable hospitalizations in the future., (© The Author 2015. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.)

Background: Lower urinary tract symptoms (LUTS) comprise storage symptoms, voiding symptoms and post-voiding symptoms. Prevalence and severity of LUTS increase with age and the progressive increase in the aged population group has emphasised the importance to our society of appropriate and effective management of male LUTS. Identification of causal mechanisms is needed to optimise treatment and uroflowmetry is the simplest non-invasive test of voiding function. Invasive urodynamics can evaluate storage function and voiding function; however, there is currently insufficient evidence to support urodynamics becoming part of routine practice in the clinical evaluation of male LUTS., Design: A 2-arm trial, set in urology departments of at least 26 National Health Service (NHS) hospitals in the United Kingdom (UK), randomising men with bothersome LUTS for whom surgeons would consider offering surgery, between a care pathway based on urodynamic tests with invasive multichannel cystometry and a care pathway based on non-invasive routine tests. The aim of the trial is to determine whether a care pathway not including invasive urodynamics is no worse for men in terms of symptom outcome than one in which it is included, at 18 months after randomisation. This primary clinical outcome will be measured with the International Prostate Symptom Score (IPSS). We will also establish whether inclusion of invasive urodynamics reduces rates of bladder outlet surgery as a main secondary outcome., Discussion: The general population has an increased life-expectancy and, as men get older, their prostates enlarge and potentially cause benign prostatic obstruction (BPO) which often requires surgery. Furthermore, voiding symptoms become increasingly prevalent, some of which may not be due to BPO. Therefore, as the population ages, more operations will be considered to relieve BPO, some of which may not actually be appropriate. Hence, there is sustained interest in the diagnostic pathway and this trial could improve the chances of an accurate diagnosis and reduce overall numbers of surgical interventions for BPO in the NHS. The morbidity, and therapy costs, of testing must be weighed against the cost saving of surgery reduction., Trial Registration: Controlled-trials.com - ISRCTN56164274 (confirmed registration: 8 April 2014).

Objectives: We investigated whether federally tax-exempt hospitals consider community health needs when deciding how much and what types of community benefits to provide., Methods: Using 2009 data from hospital tax filings to the Internal Revenue Service and the 2010 County Health Rankings, we employed both univariate and multivariate analyses to examine the relationship between community health needs and the types and levels of hospitals' community benefit expenditures. The study sample included 1522 private, tax-exempt hospitals throughout the United States., Results: We found some patterns between community health needs and hospitals' expenditures on community benefits. Hospitals located in communities with greater health needs spent more as a percentage of their operating budgets on benefits directly related to patient care. By contrast, spending on community health improvement initiatives was unrelated to community health needs., Conclusions: Important opportunities exist for tax-exempt hospitals to improve the alignment between their community benefit activities and the health needs of the community they serve. The Affordable Care Act requirement that hospitals conduct periodic community health needs assessments may be a first step in this direction.

Background: Although pay-for-performance (P4P) has become a central strategy for improving quality in US healthcare, questions persist about the effectiveness of these programs. A key question is whether quality improvement that occurs as a result of P4P programs is sustainable, particularly if incentives are removed., Objective: To investigate sustainability of performance levels following removal of performance-based incentives., Design, Setting, and Participants: Observational cohort study that capitalized on a P4P program within the Veterans Health Administration (VA) that included adoption and subsequent removal of performance-based incentives for selected inpatient quality measures. The study sample comprised 128 acute care VA hospitals where performance was assessed between 2004 and 2010., Intervention: VA system managers set annual performance goals in consultation with clinical leaders, and report performance scores to medical centers on a quarterly basis. These scores inform performance-based incentives for facilities and their managers. Bonuses are distributed based on the attainment of these performance goals., Measurements: Seven quality of care measures for acute coronary syndrome, heart failure, and pneumonia linked to performance-based incentives., Results: Significant improvements in performance were observed for six of seven quality of care measures following adoption of performance-based incentives and were maintained up to the removal of the incentive; subsequently, the observed performance levels were sustained., Limitations: This is a quasi-experimental study without a comparison group; causal conclusions are limited., Conclusion: The maintenance of performance levels after removal of a performance-based incentive has implications for the implementation of Medicare's value-based purchasing initiative and other P4P programs. Additional research is needed to better understand human and system-level factors that mediate sustainability of performance-based incentives.

Objective: To ensure optimal care for patients with schizophrenia, antipsychotic medications must be appropriately prescribed and used. Therefore, the primary objectives of this study were to identify and describe pathways for antipsychotic prescribing, assess the consistency of observed pathways with treatment guidelines, and describe variability across facilities., Methods: Data from Veterans Affairs administrative data sets from fiscal year (FY) 2003 to FY 2007 were gathered for analysis in this retrospective cohort study of antipsychotic prescribing pathways among 13 facilities across two regional networks. Patients with a new episode of care for schizophrenia or schizoaffective disorder in FY 2005 were identified, and antipsychotic prescribing history was obtained for two years before and after the index diagnosis. Demographic characteristics and distribution of comorbidities were assessed. Median medical center rates of polypharmacy were calculated and compared with Fisher's exact test., Results: Of 1,923 patients with a new episode of schizophrenia care, 1,003 (52%) had complete data on prescribing pathways. A majority (74%) of patients were prescribed antipsychotic monotherapy, and 19% received antipsychotic polypharmacy. Of patients receiving antipsychotic polypharmacy, 65% began polypharmacy within 90 days of starting any antipsychotic treatment. There was a fourfold difference in polypharmacy across facilities. Antipsychotic polypharmacy was not associated with geographic location or medical center patient volume. Clozapine utilization was low (0%-2%)., Conclusions: Retrospective examination of longitudinal prescribing patterns identified multiple antipsychotic prescribing pathways. Although most patients received guideline-concordant care, antipsychotic polypharmacy was commonly used as initial treatment, and there was substantial variability among facilities. Study findings suggest the utility of secondary data to assess treatment adaptation or switching for practical clinical trials.

Background: The mitochondrial genomes of flowering plants vary greatly in size, gene content, gene order, mutation rate and level of RNA editing. However, the narrow phylogenetic breadth of available genomic data has limited our ability to reconstruct these traits in the ancestral flowering plant and, therefore, to infer subsequent patterns of evolution across angiosperms., Results: We sequenced the mitochondrial genome of Liriodendron tulipifera, the first from outside the monocots or eudicots. This 553,721 bp mitochondrial genome has evolved remarkably slowly in virtually all respects, with an extraordinarily low genome-wide silent substitution rate, retention of genes frequently lost in other angiosperm lineages, and conservation of ancestral gene clusters. The mitochondrial protein genes in Liriodendron are the most heavily edited of any angiosperm characterized to date. Most of these sites are also edited in various other lineages, which allowed us to polarize losses of editing sites in other parts of the angiosperm phylogeny. Finally, we added comprehensive gene sequence data for two other magnoliids, Magnolia stellata and the more distantly related Calycanthus floridus, to measure rates of sequence evolution in Liriodendron with greater accuracy. The Magnolia genome has evolved at an even lower rate, revealing a roughly 5,000-fold range of synonymous-site divergence among angiosperms whose mitochondrial gene space has been comprehensively sequenced., Conclusions: Using Liriodendron as a guide, we estimate that the ancestral flowering plant mitochondrial genome contained 41 protein genes, 14 tRNA genes of mitochondrial origin, as many as 7 tRNA genes of chloroplast origin, >700 sites of RNA editing, and some 14 colinear gene clusters. Many of these gene clusters, genes and RNA editing sites have been variously lost in different lineages over the course of the ensuing ∽200 million years of angiosperm evolution.

Before a genetically modified (GM) crop can be commercialized it must pass through a rigorous regulatory process to verify that it is safe for human and animal consumption, and to the environment. One particular area of focus is the potential introduction of a known or cross-reactive allergen not previously present within the crop. The assessment of possible allergenicity uses the guidelines outlined by the Food and Agriculture Organization (FAO) and World Health Organization's (WHO) Codex Alimentarius Commission (Codex) to evaluate all newly expressed proteins. Some regulatory authorities have broadened the scope of the assessment to include all DNA reading frames between stop codons across the insert and spanning the insert/genomic DNA junctions. To investigate the utility of this bioinformatic assessment, all naturally occurring stop-to-stop frames in the non-transgenic genomes of maize, rice, and soybean, as well as the human genome, were compared against the AllergenOnline (www.allergenonline.org) database using the Codex criteria. We discovered thousands of frames that exceeded the Codex defined threshold for potential cross-reactivity suggesting that evaluating hypothetical ORFs (stop-to-stop frames) has questionable value for making decisions on the safety of GM crops., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the present series of experiments, we show that N-methyl-D-aspartate receptor (NMDAR)-driven synaptic plasticity and NO-cGMP-PKG signaling in the LA regulate the training-induced expression of ERK and the ERK-driven immediate early genes (IEGs) Arc/Arg3.1, c-Fos, and EGR-1 in the LA and the MGm/PIN. Rats receiving intra-LA infusion of the NR2B selective antagonist Ifenprodil, the NOS inhibitor 7-Ni, or the PKG inhibitor Rp-8-Br-PET-cGMPS exhibited significant decreases in ERK activation and in the training-induced expression of all three IEGs in the LA and MGm/PIN while intra-LA infusion of the PKG activator 8-Br-cGMP had the opposite effect. Remarkably, those rats given intra-LA infusion of the membrane impermeable NO scavenger c-PTIO exhibited significant decreases in ERK activation and ERK-driven IEG expression in the MGm/PIN, but not in the LA. Together with our previous experiments, these results suggest that synaptic plasticity and the NO-cGMP-PKG signaling pathway promote fear memory consolidation, in part, by regulating ERK-driven transcription in both the LA and the MGm/PIN. They further suggest that synaptic plasticity in the LA during fear conditioning promotes ERK-driven transcription in MGm/PIN neurons via NO-driven "retrograde signaling."

Advocates for physician-owned hospitals specializing in cardiac, orthopedic, and surgical services claim that these facilities induce healthy competition, stimulating improved performance among acute care hospitals. This paper examines the effect of specialty hospital entry, on one indicator of competition among hospitals: changes in service provision by general hospitals in local markets. Results suggest that general hospitals are stepping up their own offerings of services that are in direct competition with those of specialty hospitals. Entry of specialty hospitals is also associated with significantly higher growth in high-technology diagnostic imaging services in the general hospitals in those markets.

The shift from local, community-based organizations to more complex delivery systems raises questions about the community orientation and accountability of health systems and their affiliates. This study examines whether hospitals affiliated with health care systems are more or less likely to engage in practices that reflect responsibility to their local communities by providing benefits in the form of uncompensated care, community engagement, Medicaid caseload, and accessible pricing policies. Using audited state data and other sources, we performed a longitudinal analysis on a pooled cross-sectional data file for the years 1989-2003 for all hospitals in Texas, California, and Florida. Results indicate that when compared to independent hospitals, system affiliation is associated with less community benefit. However, the level of community benefit varies depending on the type of community benefit examined and the structural characteristics of the system with which a hospital is affiliated. Results further suggest that the level and type of community benefit is conditioned by the market under which system-affiliated hospitals operate.

Objective: To compare the costs of physician-owned cardiac, orthopedic, and surgical single specialty hospitals with those of full-service hospital competitors., Data Sources: The primary data sources are the Medicare Cost Reports for 1998-2004 and hospital inpatient discharge data for three of the states where single specialty hospitals are most prevalent, Texas, California, and Arizona. The latter were obtained from the Texas Department of State Health Services, the California Office of Statewide Health Planning and Development, and the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project. Additional data comes from the American Hospital Association Annual Survey Database., Study Design: We identified all physician-owned cardiac, orthopedic, and surgical specialty hospitals in these three states as well as all full-service acute care hospitals serving the same market areas, defined using Dartmouth Hospital Referral Regions. We estimated a hospital cost function using stochastic frontier regression analysis, and generated hospital specific inefficiency measures. Application of t-tests of significance compared the inefficiency measures of specialty hospitals with those of full-service hospitals to make general comparisons between these classes of hospitals., Principal Findings: Results do not provide evidence that specialty hospitals are more efficient than the full-service hospitals with whom they compete. In particular, orthopedic and surgical specialty hospitals appear to have significantly higher levels of cost inefficiency. Cardiac hospitals, however, do not appear to be different from competitors in this respect., Conclusions: Policymakers should not embrace the assumption that physician-owned specialty hospitals produce patient care more efficiently than their full-service hospital competitors.