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Many medical centers have modified their facility design to provide a safer environment for patients. From an infection control perspective, the primary objective of hospital design is to place the patient at no risk for infection while hospitalized. We describe historical landmarks about hospital design, modern facility design, and specific designs to prevent acquisition and spread of infections such as tuberculosis and aspergillosis. [ABSTRACT FROM AUTHOR]

Northwestern Memorial Hospital instituted in-house molecular typing to rapidly assess microbial clonality and integrated this typing into an infection control program. We compared data on nosocomial infections collected during 24 months before and 60 months after implementing the new program. During the intervention period, infections per 1,000 patient-days fell 13% (p=0.002) and the percentage of hospitalized patients with nosocomial infections decreased 23% (p=0.000006). In our hospital, the percentage of patients with nosocomial infections is 43% below the U.S. rate. Our typing laboratory costs approximately $400,000 per year, a savings of $5.00 for each dollar spent. [ABSTRACT FROM AUTHOR]

A systematic assessment of infections beginning early in pregnancy is necessary to determine the true role of infections in pregnancy loss, given that infections could readily arise only after fetal demise. To this end, we have prospectively determined the frequency of infections in pregnant women who were subjects in a multi-centre US study. Insulin-dependent diabetic subjects and controlled subjects were recruited either before conception (86%) or at the latest within 21 days of conception (14%). We collected data prospectively on all important risk factors and potential confounding variables, seeing 386 diabetic subjects weekly and 432 control subjects every other week during the first trimester. At each visit we inquired about untoward events and explicitly about fever or infections. We found no clinical evidence that infection occurred more often in the 116 subjects experiencing pregnancy loss as compared to the 702 having successful pregnancies. This held both for the 2 week interval in which a given loss was recognized clinically as well as in the prior 2 week interval. Similar findings were not only observed for both the control as well as diabetic subjects but also when data were stratified by genital infection only or by systemic infection only. Our prospective data suggest that the attributable risk of infection in first trimester spontaneous abortion is small. [ABSTRACT FROM AUTHOR]

Agroecosystems are domesticated ecosystems intermediate between natural ecosystems and fabricated ecosystems, and occupy nearly one-thirdof the land areas of the earth. Chemical perturbations as a result of human activity are particularly likely in agroecosystems because ofthe intensity of that activity, which include nutrient inputs intended to supplement native nutrient pools and to support greater biomassproduction and removal. At a long-term fertility trial in South-Central Wisconsin, USA, significant increases in exchangeable acidity were accompanied by decreases in cation exchange capacity (CEC), base saturation, and exchangeable Ca2+ and Mg2+ with application of ammoniacal N fertilizer. Plant analysis shows that a considerable portion of the alkalinity generated by assimilation of N (and to a lesser extent by S) is sequestered in the above-ground plantparts as organic anions and is not returned to the soil if harvested. Elemental analysis of Ca-saturated soil clays indicates an loss of 16% of the CEC of the soil clay and minor increases in Fe and Al. Thereversibility of these changes due to prolonged acidification is doubtful if the changes are due to soil weathering. [ABSTRACT FROM AUTHOR]

We reviewed data from the National Registry of Myocardial Infarction-2 to determine the differences in characteristics and outcomes in patients with acute myocardial infarction (AMI) who have undergone previous coronary artery bypass grafting (CABG), and those who have not, and between post-CABG patients who were treated with alteplase (recombinant tissue-type plasminogen activator [rt-PA]) and those who were treated with primary percutaneous transluminal coronary angioplasty (PTCA). Demographic, therapeutic, and outcome data from patients with AMI were collected at > 1,000 hospitals in the United States in collaboration with National Registry of Myocardial Infarction-2. Of the 45,925 patients receiving reperfusion therapy, 2,544 of the 39,574 treated with rt-PA (6.4%) had a history of CABG, and 375 of the 6,351 treated with primary PTCA (5.9%) had a history of CABG. Patients with a history of CABG were older, more likely to be men, and had more comorbidities, but prior CABG was still an independent predictor of mortality after multivariate regression analysis (odds ratio 1.23; 95% confidence interval 1.05 to 1.44). Among the post-CABG patients who received rT-PA or underwent PTCA, there was no significant difference in in-hospital mortality rate or the combined end point of death and nonfatal stroke. Thus, (1) prior CABG is an independent predictor of mortality, and (2) for post-CABG patients with AMI who are not in shock and who are lytic-eligible, reperfusion therapy with rt-PA and PTCA result in similar outcomes with regard to in-hospital mortality and the combined end point of death and nonfatal stroke. [ABSTRACT FROM AUTHOR]

Background and Objectives: Resident burnout may affect career choices and empathy. We examined predictors of burnout among family medicine residents., Methods: We used data from the 2019-2021 American Board of Family Medicine Initial Certification Questionnaire, which is required of graduating residents. Burnout was a binary variable defined as reporting callousness or emotional exhaustion once a week or more. We evaluated associations using bivariate and multilevel multivariable regression analyses., Results: Among 11,570 residents, 36.4% (n=4,211) reported burnout. This prevalence did not significantly vary from 2019 to 2021 and was not significantly attributable to the residency program (ICC=0.07). Residents identifying as female reported higher rates of burnout (39.0% vs 33.4%, AOR=1.29 [95% CI 1.19-1.40]). Residents reporting Asian race (30.5%, AOR=0.78 [95% CI 0.70-0.86]) and Black race (32.3%, AOR=0.71 [95% CI 0.60-0.86]) reported lower odds of burnout than residents reporting White race (39.2%). We observed lower rates among international medical graduates (26.7% vs 40.3%, AOR=0.54 [95% CI 0.48-0.60]), those planning to provide outpatient continuity care (36.0% vs 38.7%, AOR=0.77 [95% CI 0.68-0.86]), and those at smaller programs (31.7% for <6 residents per class vs 36.3% for 6-10 per class vs 40.2% for >10 per class). Educational debt greater than $250,000 was associated with higher odds of burnout than no debt (AOR=1.29 [95% CI 1.15-1.45])., Conclusions: More than one-third of recent family medicine residents reported burnout. Odds of burnout varied significantly with resident and program characteristics.

Complaints provide important information to consumers about nursing homes (NHs), but how substantiated complaints map onto deficiency citations is unknown. The purpose of this study is to understand the relationship between substantiated complaints and deficiency citations. Federally collected NH complaint and inspection records were obtained to identify all single allegation, substantiated complaints for NHs across the U.S. in 2017. Overall, the 369 complaint allegations in our sample resulted in a total of 585 deficiencies at the inspection stage; however, 35.2% of the allegations led to no deficiencies. Nearly two-thirds of the 369 substantiated single allegation complaints were categorized at the intake stage as quality of care (31.7%), resident abuse (17.3%), or resident neglect (14.1%). Further, 18% of the inspection deficiencies originated with complaint allegations that were prioritized as immediate jeopardy at intake, but of these, 71.4% were determined upon inspection to constitute "no actual harm with potential for more than minimal harm." These results provide evidence that complaints have the potential to provide unique valuable information on NH quality of care and draw regulatory attention to consumers' concerns. Future studies should include qualitative research concerning complaint processes by conducting interviews/surveys of complainants, NH staff/administrators, long-term care ombudsmen, and state officials.

Objective: Hypothermia is common among trauma patients and can lead to a serious rise in morbidity and mortality. This study was performed to investigate the effect of active and passive warming measures implemented in the prehospital phase on the body temperature of trauma patients., Methods: In a multicenter, multinational prospective observational design, the effect of active and passive warming measures on the incidence of hypothermia was investigated. Adult trauma patients who were transported by helicopter emergency medical services (HEMS) or ground emergency medical services with an HEMS physician directly from the scene of injury were included. Four HEMS/ground emergency medical services programs from Canada, the United States, and the Netherlands participated., Results: A total of 80 patients (n = 20 per site) were included. Eleven percent had hypothermia on presentation, and the initial evaluation occurred predominantly within 60 minutes after injury. In-line fluid warmers and blankets were the most frequently used active and passive warming measures, respectively. Independent risk factors for a negative change in body temperature were transportation by ground ambulance (odds ratio = 3.20; 95% confidence interval, 1.06-11.49; P = .03) and being wet on initial presentation (odds ratio = 3.64; 95% confidence interval, 0.99-13.36; P = .05)., Conclusion: For adult patients transported from the scene of injury to a trauma center, active and passive warming measures, most notably the removal of wet clothing, were associated with a favorable outcome, whereas wet patients and ground ambulance transport were associated with an unfavorable outcome with respect to temperature., (Copyright © 2023 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Background: Reducing health inequities in marginalized populations, including people with Medicaid insurance, requires care transformation to address medical and social needs that is supported and incentivized by tailored payment methods. Collaboration across health care stakeholders is essential to overcome health system fragmentation and implement sustainable reform in the United States (U.S.). This paper explores how multi-stakeholder teams operationalized the Roadmap to Advance Health Equity model during early stages of their journey to (a) build cultures of equity and (b) integrate health equity into care transformation and payment reform initiatives., Methods: Advancing Health Equity: Leading Care, Payment, and Systems Transformation is a national program in the U.S. funded by the Robert Wood Johnson Foundation that brings together multi-stakeholder teams to design and implement initiatives to advance health equity. Each team consisted of representatives from state Medicaid agencies, Medicaid managed care organizations, and health care delivery organizations in seven U.S. states. Between June and September 2021, semi-structured interviews were conducted with representatives ( n = 23) from all seven teams about experiences implementing the Roadmap to Advance Health Equity model with technical assistance from Advancing Health Equity., Results: Facilitators of building cultures of equity included (1) build upon preexisting intra-organizational cultures of equity, (2) recruit and promote diverse staff and build an inclusive culture, and (3) train staff on health equity and anti-racism. Teams faced challenges building inter-organizational cultures of equity. Facilitators of identifying a health equity focus area and its root causes included (1) use data to identify a health equity focus and (2) overcome stakeholder assumptions about inequities. Facilitators of implementing care transformation and payment reform included (1) partner with Medicaid members and individual providers and (2) support and incentivize equitable care and outcomes with payment. Facilitators of sustainability planning included (1) identify evidence of improved health equity focus and (2) maintain relationships among stakeholders. Teams faced challenges determining the role of the state Medicaid agency., Conclusions: Multi-stakeholder teams shared practical strategies for implementing the Roadmap to Advance Health Equity that can inform future efforts to build intra- and inter-organizational cultures of equity and integrate health equity into care delivery and payment systems., Competing Interests: MC co-chairs the Centers for Medicare and Medicaid Services Health Care Payment Learning and Action Network Health Equity Advisory Team and he is a member of the Bristol-Myers Squibb Company Health Equity Advisory Board and Blue Cross Blue Shield Health Equity Advisory Panel. SP and AS were employed by the company Center for Health Care Strategies. JM was employed by the company Institute for Medicaid Innovation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Thorndike, Peterson, Spitzer, Patel, Smithey, Moore, Cook and Chin.)

Background and Objectives: The quality of training in rural family medicine (FM) residencies has been questioned. Our objective was to assess differences in academic performance between rural and urban FM residencies., Methods: We used American Board of Family Medicine (ABFM) data from 2016-2018 residency graduates. Medical knowledge was measured by the ABFM in-training examination (ITE) and Family Medicine Certification Examination (FMCE). The milestones included 22 items across six core competencies. We measured whether residents met expectations on each milestone at each assessment. Multilevel regression models determined associations between resident and residency characteristics milestones met at graduation, FMCE score, and failure., Results: Our final sample was 11,790 graduates. First-year ITE scores were similar between rural and urban residents. Rural residents passed their initial FMCE at a lower rate than urban residents (96.2% vs 98.9%) with the gap closing upon later attempts (98.8% vs 99.8%). Being in a rural program was not associated with a difference in FMCE score but was associated with higher odds of failure. Interactions between program type and year were not significant, indicating equal growth in knowledge. The proportions of rural vs urban residents who met all milestones and each of six core competencies were similar early in residency but diverged over time with fewer rural residents meeting all expectations., Conclusions: We found small, but persistent differences in measures of academic performance between rural- and urban-trained FM residents. The implications of these findings in judging the quality of rural programs are much less clear and warrant further study, including their impact on rural patient outcomes and community health.

Background and Objective: The associations between training length and clinical knowledge are unknown. We compared family medicine in-training examination (ITE) scores among residents who trained in 3- versus 4-year programs and to national averages over time., Methods: In this prospective case-control study, we compared the ITE scores of 318 consenting residents in 3-year programs to 243 who completed 4 years of training between 2013 through 2019. We obtained scores from the American Board of Family Medicine. The primary analyses involved comparing scores within each academic year according to length of training. We used multivariable linear mixed effects regression models adjusted for covariates. We performed simulation models to predict ITE scores after 4 years of training among residents who underwent only 3 years of training., Results: At baseline postgraduate year-1 (PGY1), the estimated mean ITE scores were 408.5 for 4-year programs and 386.5 for 3-year programs, a 21.9 point difference (95% CI=10.1-33.8). At PGY2 and PGY3, 4-year programs scored 15.0 points higher and 15.6 points higher, respectively. When extrapolating an estimated mean ITE score for 3-year programs, 4-year programs would still score 29.4 points higher (95% CI=15.0-43.8). Our trend analysis revealed those in 4-year programs had a slightly lesser slope increase compared to 3-year programs in the first 2 years. Their drop-off in ITE scores is less steep in later years, though these differences were not statistically significant., Conclusions: While we found significantly higher absolute ITE scores in 4 versus 3-year programs, these increases in PGY2, PGY3 and PGY4 may be due to initial differences in PGY1 scores. Additional research is needed to support a decision to change the length of family medicine training.

Background and Objectives: Demand for geriatric care is increasing due to aging population. Trends in maintaining certification in geriatrics are unreported. Our objective was to describe the historic trend of family physicians who certified in geriatric medicine (FPs-GM) since 1988 and to assess differences in practice patterns between FPs-GM and family physicians (FPs)., Methods: We performed a retrospective descriptive study using administrative data collected by the American Board of Family Medicine (ABFM). The study population was family physicians registering to continue their ABFM certification from 2017 to 2019. Medicare public use billing data was linked to ABFM administrative data on certification history. We used univariate analysis for descriptive analysis and logistic regression to identify contributors of recertification in geriatrics., Results: We identified a total of 3,207 FPs-GM between 1988 and 2019. More than half maintained GM certification since 2009 (57%), with male gender, White race, and urban practice associated with maintaining GM certification; 61% of their patients were older adults. FPs-GM were more likely to be in an academic practice setting with nearly half (53%) also practicing in hospitals or nursing homes. In the adjusted regression model, younger FPs or FPs who treat more older patients were significantly more likely to be recertified in geriatrics whereas other demographics and practice characteristics were not significant., Conclusions: Most FPs who recently earned GM certification tended to retain certification since the required accredited fellowship started in 1995.

Introduction: This nationwide study builds on prior research, which suggests that Federally Qualified Health Centers (FQHCs) and other primary care providers are associated with increased access to opioid use disorder (OUD) treatment. We compare health care utilization, spending, and quality for Medicaid patients diagnosed with OUD who receive primary care at FQHCs and Medicaid patients who receive most primary care in other settings, such as physician offices (non-FQHCs). We hypothesized that the integrated care model of FQHCs would be associated with greater access to medication for opioid use disorder (MOUD) and/or behavioral health therapy and lower rates of potentially inappropriate co-prescribing., Methods: This cross-sectional study examined 2012 Medicaid Analytic eXtract files for patients diagnosed with OUD receiving most (>50%) primary care at FQHCs (N = 37,142) versus non-FQHCs (N = 196,712) in all 50 states and Washington DC. We used propensity score overlap weighting to adjust for measurable confounding between patients who received care at FQHCs versus non-FQHCs and increase generalizability of findings given variation in Medicaid programs and substance use policies across states., Results: FQHC patients displayed higher primary care utilization and fee-for-service spending, and similar or lower utilization and fee-for-service spending for other health service categories. Contrary to our hypotheses, non-FQHC patients were more likely to receive timely (≤90 days) MOUD (buprenorphine, methadone, naltrexone, or suboxone) (Relative Risk [RR] = 1.10, 95% CI: 1.07, 1.12) and more likely be retained in medication treatment (>180 days) (RR = 1.12, 95% CI: 1.09, 1.14). However, non-FQHC patients were less likely to receive behavioral health therapy (mental health or substance use therapy) (RR = 0.90, 95% CI: 0.88, 0.92) and less likely to remain in behavioral health treatment (RR = 0.92, 95% CI: 0.89, 0.94). Non-FQHC patients were more likely to fill potentially inappropriate prescriptions of benzodiazepines and opioids after OUD diagnosis (RR = 1.35, 95% CI: 1.30, 1.40)., Conclusions: Observed patterns suggest that Medicaid patients diagnosed with OUD who obtained primary care at FQHCs received more integrated care compared to non-FQHC patients. Greater care integration may be associated with increased access to behavioral health therapy and quality of care (lower potentially inappropriate co-prescribing) but not necessarily greater access to MOUD., Competing Interests: The authors have declared that no competing interests exist.

Objective: To compare physician-level versus practice-level primary care continuity and their association with expenditure and acute care utilization among Medicare beneficiaries and evaluate whether continuity of outpatient primary care at either/both physician or/and practice level could be useful quality measures., Data Source: Medicare Fee-For-Service claims data for community dwelling beneficiaries without end-stage renal disease who were attributed to a national random sample of primary care practices billing Medicare (2011-2017)., Study Design: Retrospective secondary data analysis at per Medicare beneficiary per year level. We used multivariable linear regression with practice-level fixed effects to estimate continuity of care score at physician versus practice level and their associations with outcomes., Data Collection/extraction Method: We calculated clinician- and practice-level Bice-Boxerman continuity of care index scores, ranging from 0 to 1, using primary care outpatient claims. Medicare expenditures, hospital admissions, emergency department (ED) visits, and readmissions were obtained from the Medicare Beneficiary Summary File: Cost and Utilization Segment. Ambulatory care sensitive conditions (ACSC) were defined using diagnosis codes on inpatient claims., Principal Findings: We studied 2,359,400 beneficiaries who sought care from 13,926 physicians. Every 0.1 increase in physician continuity score was associated with a $151 reduction in expenditure per beneficiary per year (p < 0.01), and every 0.1 increase in practice continuity score was associated with $282 decrease (p < 0.01) per beneficiary per year. Both physician- and practice-level continuity were associated with lower Medicare expenditures among small, medium, and large practices. Both physician- and practice-level continuity were associated with lower probabilities of hospitalization, ED visit, admissions for ACSC, and readmission., Conclusions: Primary care continuity of care could serve as a potent value-based care quality metric. Physician-level continuity is a unique value center that cannot be supplanted by practice-level continuity., (© 2022 Health Research and Educational Trust.)

Objective: Thea aim of this study was to explore the relationship between Florida nursing home and assisted living facility characteristics and their ability to comply with a new emergency power rule in the aftermath of Hurricane Irma., Methods: This study used characteristics data on Florida nursing homes (NHs) ( N = 680) and assisted living facilities (ALFs) ( N = 2940) in operation between September 2017 and January 2019. Logistic regressions were used to determine whether certain characteristics were associated with compliance with the emergency power rule by January 1, 2019., Results: A total of 219 (32.9%) NHs and 2219 (75.5%) ALFs had an emergency power plan implemented by January 1, 2019. Results suggest having a dementia care unit increased the odds of compliance for NHs, while chain membership, for-profit status, and a higher reliance on Medicaid decreased the odds. Additionally, smaller size, mental health specialty license, and higher reliance on supplemental state funding increased the odds of compliance for ALFs, while nursing care specialty license and for-profit status decreased the odds of compliance., Conclusions: Policy implications from these results include informing policy-makers on the barriers faced by NHs and ALFs to implement a new regulation that may cause financial difficulties and compromise quality care.

Nonprofit hospitals have attracted scrutiny for aggressive collection activities against patients, which persist despite the Patient Protection and Affordable Care Act's attempt to limit particularly egregious practices, called "extraordinary collection actions" (ECAs). This study examines the prevalence of ECAs and characteristics of nonprofit hospitals that reported this behavior as of 2016. Using Community Benefit Insight data, characteristics of hospitals that reported ECAs are compared with hospitals that did not report these practices. ECAs include reporting patient debt to credit agencies, filing lawsuits, placing liens on residences, and issuing civil arrest. Predictors of ECAs among nonprofit hospitals are identified using logistic regression analysis. The prevalence of ECAs is examined for the 2010-2016 time period, and nonprofit hospitals that reported ECAs are mapped to show the geographic distribution. Hospitals reporting ECAs significantly differed in total revenue, system membership, bed size, urban location, financial assistance policy use, and use of poverty guidelines for discounted care. In full logistic regression models, lower total hospital revenue was a significant predictor of ECAs. As social workers, it is vital to understand the landscape of nonprofit hospital collection actions to advocate for policy that protects patients from predatory practices while holding nonprofit hospitals accountable., (© 2021 National Association of Social Workers.)

This perspective addresses the challenges that assisted living (AL) providers face concerning federal guidelines to prevent increased spread of COVID-19. These challenges include restriction of family visitation, use of third-party providers as essential workers, staffing guidelines, transfer policies, and rural AL hospitalizations. To meet these challenges we recommend that AL providers incorporate digital technology to maintain family-resident communication. We also recommend that states adopt protocols that limit the number of AL communities visited by home health care workers in a 14-day period, appeal to the federal government for hazard pay for direct care workers, and to extend the personal care attendant program to AL. It is further recommended that states work with AL communities to implement COVID-19 comprehensive emergency management plans that are well-coordinated with local emergency operation centers to assist with transfers to COVID-19 specific locations and to assist in rural areas with hospital transfers. Together, these recommendations to AL providers and state and federal agencies address the unique structure and needs of AL and would enable AL communities to be better prepared to care for and reduce those infected with COVID-19.

Objective: Nearly 10% of all hospitalized children have a primary behavioral health diagnosis, but the effectiveness of treatment can be limited by caregivers' challenges navigating the behavioral health system. In this study, we assessed a novel peer-support intervention ("parent partners") designed for the caregivers of children admitted to an inpatient psychiatric unit., Methods: We used a mixed-methods approach including 1) document review and interviews to assess implementation and 2) a difference-in-differences analysis using claims for Medicaid-enrolled children admitted to the intervention inpatient psychiatric unit and matched comparison children admitted to other inpatient psychiatric units to assess the impacts on health care use after discharge., Results: Ninety-six percent of caregivers who were offered the intervention engaged with a parent partner. The primary challenges to implementation were accommodating the needs of parent partners to address behavioral health crises among their own children and initial limited engagement from behavioral health clinicians. The intervention leaders reported success in addressing these through adjustments to staffing policies, training parent partners in engagement with clinicians, and incorporating parent partners into team rounds. We did not find a statistically significant difference in follow-up outpatient behavioral health visits (adjusted treatment to comparison difference +3% [90% CI = -2%, +9%]), readmissions (+5% [-33%, +43%]), or behavioral health ED visits (-15% [-44%, +14%])., Conclusions: This novel intervention was implemented successfully, and although our study did not find statistically significant impacts on health care use after discharge, the findings for ED visits are suggestive of benefits. Parent peer support in inpatient settings warrants additional investigation., (Copyright © 2019 Academic Pediatric Association. All rights reserved.)

Description: The American Diabetes Association (ADA) annually updates its Standards of Medical Care in Diabetes to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of patients with diabetes., Methods: The ADA Professional Practice Committee comprises physicians, adult and pediatric endocrinologists, diabetes educators, registered dietitians, epidemiologists, pharmacists, and public health experts. To develop the 2019 standards, the committee continuously searched MEDLINE through November 2018 to consider and review studies, particularly high-quality trials including persons with diabetes, for potential incorporation into recommendations. It also solicited feedback from the larger clinical community., Recommendations: This synopsis focuses on selected guidance relating to use of diabetes technology in adults with diabetes. Recommendations address self-monitoring of blood glucose, continuous glucose monitors, and automated insulin delivery systems.

Importance: Obesity is associated with an increased risk of breast cancer, including the estrogen receptor (ER)-positive subtype in postmenopausal women. Whether excess adiposity is associated with increased risk in women with a normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown., Objective: To investigate the association between body fat and breast cancer risk in women with normal BMI., Design, Setting, and Participants: This ad hoc secondary analysis of the Women's Health Initiative (WHI) clinical trial and observational study cohorts was restricted to postmenopausal participants with a BMI ranging from 18.5 to 24.9. Women aged 50 to 79 years were enrolled from October 1, 1993, through December 31, 1998. Of these, 3460 participants underwent body fat measurement with dual-energy x-ray absorptiometry (DXA) at 3 US designated centers with follow-up. At a median follow-up of 16 years (range, 9-20 years), 182 incident breast cancers had been ascertained, and 146 were ER positive. Follow-up was complete on September 30, 2016, and data from October 1, 1993, through September 30, 2016, was analyzed August 2, 2017, through August 21, 2018., Main Outcomes and Measures: Body fat levels were measured at baseline and years 1, 3, 6, and 9 using DXA. Information on demographic data, medical history, and lifestyle factors was collected at baseline. Invasive breast cancers were confirmed via central review of medical records by physician adjudicators. Blood analyte levels were measured in subsets of participants., Results: Among the 3460 women included in the analysis (mean [SD] age, 63.6 [7.6] years), multivariable-adjusted hazard ratios for the risk of invasive breast cancer were 1.89 (95% CI, 1.21-2.95) for the highest quartile of whole-body fat and 1.88 (95% CI, 1.18-2.98) for the highest quartile of trunk fat mass. The corresponding adjusted hazard ratios for ER-positive breast cancer were 2.21 (95% CI, 1.23-3.67) and 1.98 (95% CI, 1.18-3.31), respectively. Similar positive associations were observed for serial DXA measurements in time-dependent covariate analyses. Circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides were higher, whereas levels of high-density lipoprotein cholesterol and sex hormone-binding globulin were lower in those in the uppermost vs lowest quartiles of trunk fat mass., Conclusions and Relevance: In postmenopausal women with normal BMI, relatively high body fat levels were associated with an elevated risk of invasive breast cancer and altered levels of circulating metabolic and inflammatory factors. Normal BMI categorization may be an inadequate proxy for the risk of breast cancer in postmenopausal women., Trial Registration: ClinicalTrials.gov identifier: NCT00000611.

Objectives: To assess bone marrow (BM) sampling in academic medical centers., Methods: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed., Results: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent., Conclusions: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

Background: The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion., Methods: A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system. The implanted pumps were refilled percutaneously at least every 12 weeks. The primary end point was the rate of catheter-related complications using the new model 10642 catheter compared with a predefined objective performance criterion of 2.5 per 1,000 patient-days based on the literature., Results: Patients (n = 60) with severe PAH (World Health Organization group 1) receiving a stable dose of IV treprostinil for at least 4 weeks received an implant device and were followed up for 12.1 ± 4.4 months. Six catheter-related complications occurred, corresponding to a complication rate of 0.27 per 1,000 patient-days. The 97.5% upper one-sided confidence bound of 0.59 was less than the predefined criterion of 2.5 per 1,000 patient-days (P < .0001). Plasma treprostinil levels at 1 week postimplantation were highly correlated with baseline levels (r = 0.91; P < .0001). The delivery system management time as reported by the patients was 2.5 ± 1.7 hours per week preimplantation, and this time decreased to 0.6 ± 0.8 hour per week at 6 months' postimplantation (P < .0001). All patients rated overall satisfaction with the implantable system as good, very good, or excellent at 6 weeks and 6 months. There were no catheter-related bloodstream infections or catheter occlusions., Conclusions: The implantable intravascular delivery system delivered treprostinil to patients with PAH with a low rate of catheter-related complications and a high rate of patient satisfaction., Trial Registry: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: From February 21, 2006, through September 24, 2013, the Centers for Medicare & Medicaid Services (CMS) required, via the National Coverage Determination manual, that bariatric surgery be performed only in hospitals that had been designated as a Center of Excellence (COE). The effect of this certification requirement on access to bariatric surgery has been reported only anecdotally., Objective: To investigate whether the COE certification requirement proved to be a barrier to patients' access to bariatric surgical procedures., Design, Setting, and Participants: Using the National Inpatient Sample, we retrospectively identified patients who underwent bariatric surgery from January 1, 2006, through December 31, 2011., Exposure: Bariatric surgery., Main Outcomes and Measures: Logistic regression and χ² tests were used to examine differences in patients' sociodemographic characteristics over time., Results: A total of 134,227 bariatric surgical patients were identified. The proportion of the population who were older than 64 years increased from 2.9% in 2006 to 7.0% in 2011 (P < .001) and there was a decrease in the proportion of patients who were 49 years and younger (P < .001). The percentage of female patients who underwent bariatric surgery decreased from 80.4% to 78.1% (P < .001) and the percentage of patients who were classified as black, Hispanic, or Asian or Pacific Islander increased from 12.3% to 15.1% (P < .001), 9.7% to 12.5% (P < .001), and 0.3% to 0.4% (P < .001), respectively. The proportion of patients with Medicare increased from 8.5% to 16.3% (P < .001) and those with Medicaid from 6.6% to 11.8% (P < .001). The percentage of patients with private insurance declined from 72.4% to 63.3% (P < .001). The proportion of patients in the lowest income quartile increased from 20.7% to 22.9% (P < .001) while those in the highest income quartile decreased from 25.8% to 23.9% (P < .001)., Conclusions and Relevance: The COE certification requirement by CMS did not appear to limit access to bariatric surgery. Future studies should determine whether CMS's recent (2013) change in policy (ie, removing the mandatory COE certification for bariatric surgical insurance coverage) might sacrifice patient safety without addressing the real cause of limited access to health care.

Background: Accreditation reviews of medical schools typically occur at fixed intervals and result in a summative judgment about compliance with predefined process and outcome standards. However, reviews that only occur periodically may not be optimal for ensuring prompt identification of and remediation of problem areas., Aims: To identify the factors that affect the ability to implement a continuous quality improvement (CQI) process for the interval review of accreditation standards., Methods: Case examples from the United States, Canada, the Republic of Korea and Taiwan, were collected and analyzed to determine the strengths and challenges of the CQI processes implemented by a national association of medical schools and several medical school accrediting bodies. The CQI process at a single medical school also was reviewed., Results: A functional CQI process should be focused directly on accreditation standards so as to result in the improvement of educational quality and outcomes, be feasible to implement, avoid duplication of effort and have both commitment and resource support from the sponsoring entity and the individual medical schools., Conclusions: CQI can enhance educational program quality and outcomes, if the process is designed to collect relevant information and the results are used for program improvement.

As forensic psychiatry and forensic psychology have grown and matured, the range of specialized services provided by each has expanded. In addition to traditional services such as forensic mental health assessments in criminal, family, and civil contexts, forensic specialists are now involved in delivering services in the community that include (in the criminal justice context) assessment for diversion into specialized probation or problem-solving courts, rehabilitation needs upon reentry (including specialized parole), and risk assessment for particular populations such as sexual offenders. Specialized forensic treatment services include those provided to clients under the jurisdiction of problem-solving courts or parole/probation. Similar specialized assessment and treatment services may be provided for juveniles. The nature of such service needs underscores the importance of the university-based forensic clinic as one source of specialized forensic services in the community. Such clinics are based in universities, directed by supervising faculty, and offer services provided in part by forensic trainees (psychiatric residents and forensic fellows; psychology doctoral students, interns, and post-doctoral fellows). The structure and operations of such clinics are described, with different models provided. Implications for specialized training, forensic practice, and research are discussed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

CFOs can take four steps to help their organizations align successfully and cost-effectively with physicians: Understand the type of alignment required for the organization. Determine the right strategies for strengthening the organization's alignment gaps. Execute successfully. Monitor consistently and systematically.

During the spring of 2009, pandemic influenza A (H1N1) virus (pH1N1) was recognized and rapidly spread worldwide. To describe the geographic distribution and patient characteristics of pH1N1-associated deaths in the United States, the Centers for Disease Control and Prevention requested information from health departments on all laboratory-confirmed pH1N1 deaths reported from 17 April through 23 July 2009. Data were collected using medical charts, medical examiner reports, and death certificates. A total of 377 pH1N1-associated deaths were identified, for a mortality rate of .12 deaths per 100,000 population. Activity was geographically localized, with the highest mortality rates in Hawaii, New York, and Utah. Seventy-six percent of deaths occurred in persons aged 18-65 years, and 9% occurred in persons aged ≥ 65 years. Underlying medical conditions were reported for 78% of deaths: chronic lung disease among adults (39%) and neurologic disease among children (54%). Overall mortality associated with pH1N1 was low; however, the majority of deaths occurred in persons aged <65 years with underlying medical conditions.

The United States is undertaking a major expansion of comparative effectiveness research, with the potential to achieve systemwide improvements in health care quality, outcomes, and resource allocation. However, to achieve these improvements in children's health and health care, comparative effectiveness research needs to be targeted, designed, conducted, and reported in ways that are responsive to the unique circumstances of children and adolescents. These include clinically important differences in the type and course of disease in children; demographic differences between the overall child and adult population in the United States, such as racial and ethnic makeup; and methodological issues involving study design. Our overarching point is that the base of evidence in pediatrics must not fall even further behind that for the adult population in an era of rapid advancement and funding of comparative effectiveness research.

The first U.S. multicenter clinical trial to assess the performance of the Cepheid Xpert MRSA assay (Xpert MRSA) was conducted. The assay is a qualitative test designed for the rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) directly from nares swabs. This novel test combines integrated nucleic acid extraction and automated real-time PCR for the detection of a MRSA-specific signature sequence. A total of 1,077 nares specimens were collected from seven geographically distinct health care sites across the United States with prevalence rates ranging from 5.2% to 44%. Nares specimens were tested by (i) the Xpert MRSA assay, (ii) direct culture on CHROMagar MRSA medium (direct CM culture), and (iii) broth-enriched culture (Trypticase soy broth with 6.5% sodium chloride) followed by plating onto CHROMagar MRSA medium (broth-enriched CM culture). When direct CM culture was designated the reference method, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Xpert MRSA assay were 94.3%, 93.2%, 73.0%, and 98.8%, respectively. When broth-enriched CM culture was used as the reference method, the clinical sensitivity, specificity, PPV, and NPV of the Xpert MRSA assay were 86.3%, 94.9%, 80.5%, and 96.6%, respectively. The BD GeneOhm MRSA (BDGO) assay was performed as a comparative molecular method. No statistical performance differences were observed between the Xpert MRSA and BDGO assays when they were compared to culture methods. From this large-scale, multicenter clinical comparison, we conclude that the Xpert MRSA assay is a simple, rapid, and accurate method for performing active surveillance for MRSA in a variety of health care populations.

Objective: To determine the prevalence of central venous catheter (CVC) use among patients both within and outside the ICU setting., Design: A 1-day prevalence survey of CVC use among adult inpatients at six medical centers participating in the Prevention Epicenter Program of the CDC. Using a standardized form, observers at each Epicenter performed a hospital-wide survey, collecting data on CVC use., Setting: Inpatient wards and ICUs of six large urban teaching hospitals., Results: At the six medical centers, 2,459 patients were surveyed; 29% had CVCs. Among the hospitals, from 43% to 80% (mean, 59.3%) of ICU patients and from 7% to 39% (mean, 23.7%) of non-ICU patients had CVCs. Despite the lower rate of CVC use on non-ICU wards, the actual number of CVCs outside the ICUs exceeded that of the ICUs. Most catheters were inserted in the subclavian (55%) or jugular (22%) site, with femoral (6%) and peripheral (15%) sites less commonly used. The jugular (33.0% vs 16.6%; P < .001) and femoral (13.8% vs 2.7%; P < .001) sites were more frequently used in ICU patients, whereas peripherally inserted (19.9% vs 5.9%; P < .001) and subclavian (60.7% vs 47.3%; P < .001) catheters were more commonly used in non-ICU patients., Conclusions: Current surveillance and infection control efforts to reduce morbidity and mortality associated with bloodstream infections concentrate on the high-risk ICU patients with CVCs. Our survey demonstrated that two-thirds of identified CVCs were not in ICU patients and suggests that more efforts should be directed to patients with CVCs who are outside the ICU.

Articular cartilage has a limited potential to repair. Unsatisfactory results with current treatment methods (e.g. osteochondral autografts, drilling or microfracturing) has triggered the development of new cartilage restoration techniques including autologous cell transplantation (mesenchymal stem cells or chondrocytes) with or without supporting scaffolds. Autologous chondrocyte transplantation (ACT) was first used in humans in 1987 and the first pilot was published in 1994. Two years after transplantation, 14 of the 16 patients with femoral condyle transplants had a restored joint function and 11 of 15 femoral transplants demonstrated a hyaline repair tissue. Results from patellar transplants were less encouraging. To date, we have treated over 1000 and other groups over 6000 patients. The technique gives stable long-term results with a high percentage of good to excellent results (84-90%) in patients with different types of single femoral condyle lesions, whereas in patients with other types of lesions in the knee it is less successful (average 74%). A better understanding of the repair mechanism induced by the cultured chondrocytes and the regulatory mechanisms controlling chondrogenic differentiation combined with identification and culture of stem cells with chondrogenic potential will be the key to new cartilage treatments.

A member of the Enterobacteriaceae initially identified as Kluyvera cryocrescens by the MicroScan Gram-Negative Combo 13 panel caused an outbreak of nosocomial infections in four patients (pneumonia, n = 2; urinary tract infection, n = 1; wound infection, n = 1) and urinary tract colonization in one patient. When the strains were tested by the Enteric Reference Laboratory of the Centers for Disease Control and Prevention, biochemical results were most compatible with Yersinia intermedia, Kluyvera cryocrescens, and Citrobacter farmeri but identification scores were low and test results were discrepant. However, when the biochemical test profile was placed in the computer database as a new organism, all strains were identified as the organism with high identification scores (0. 999968 to 0.999997) and no discrepant test results. By 16S rRNA sequence analysis the organism clustered most closely with, but was distinct from, Citrobacter farmeri and Citrobacter amalonaticus. Based on its unique biochemical profile and rRNA sequence, this organism is designated Enteric Group 137. Restriction endonuclease analysis and taxonomic antibiograms of strains causing the outbreak demonstrated a single clone of Enteric Group 137, and antibiotic susceptibility testing revealed the presence of extended-spectrum beta-lactamase (ESBL) resistance. Enteric Group 137 appears to be a new opportunistic pathogen that can serve as a source of ESBL resistance in the hospital.

Objectives: This study examined the validity of the Complications Screening Program (CSP) by testing whether (1) ICD-9-CM codes used to identify a complication are coded completely and accurately and (2) the CSP algorithm successfully separates conditions present on admission from those occurring in the hospital., Methods: We compared diagnosis and procedure codes contained in the Medicare claim with codes abstracted from an independent re-review of more than 1,200 medical records from Connecticut and California., Results: Eighty-nine percent of the surgical cases and 84% of the medical cases had their CSP trigger codes corroborated by re-review of the medical record. For 13% of the surgical cases and 58% of the medical cases, the condition represented by the code was judged to be present on admission rather than occurring in-hospital. The positive predictive value of the claim was greater than 80% for the surgical risk pool, suggesting the value of the CSP as a screening tool., Conclusions: The CSP has validity as a screen for most surgical complications but only for 1 medical complication. The CSP does not have validity as a "stand-alone" tool to identify more than a few in-hospital surgery-related events. The addition of an indicator to the Medicare claim to capture the timing of secondary diagnoses would improve the validity of the CSP for identifying both surgical and medical in-hospital events.

Viewing ethics in surgical practice as applying critical thinking to issues of human values leads to 4 levels of consideration: the individual patient, the surgeon, surgical research and education, and surgical organizations. This perspective starts with quantitative and qualitative feedback from patients, studies of the process of surgical decision making, and understanding how surgeons matter in preoperative counseling and postoperative recovery. Surgeons should become as active in research on the psychosocial aspects of surgical care as they are in research on the biological. Based on this information, surgical training should become explicit in preparing surgeons for patient-centered management of surgical care. Finally, surgical organizations can help by recognizing research in the human values domain, setting standards that recognize feedback from patients, and addressing more formally the needs of underserved populations. This approach fails to give the basis for clear answers but gives priority to more understanding of the moral dilemmas faced by patients and their surgeons.

Injuries are the leading killer of children in the United States, at a rate significantly higher than in other industrialized countries. In this article, we outline how a behaviorally and developmentally based model of prevention may assist in determining effective interventions for various injury risks. Two conclusions emerge: (a) the strength of perceived costs and consequences for taking effective safety actions greatly influences the probability that they will be implemented; and (b) intervening at the most developmentally appropriate time is likely to result in more effective outcomes. Further, clinical psychologists are uniquely suited to assess contingencies that maintain unsafe practices, but we need to enlist the participation of citizens and other professionals to mount persuasive intervention campaigns. Despite strong demonstration projects, childhood injury reduction has lagged behind other public health endeavors. Obstacles to injury prevention include (a) the diffusion of injury threats, complicating the identification of effective targets for intervention; (b) the tendency of parents and even some health professionals to regard injuries as products of fate, which fosters complacency; (c) the failure of U.S. social service policy to support preventive strategies; and (d) an American cultural tradition of opposing regulation. Suggestions for improved public policy and intervention procedures are advanced.

Context: Previous studies have documented that cancer patients tend to overestimate the probability of long-term survival. If patient preferences about the trade-offs between the risks and benefits associated with alternative treatment strategies are based on inaccurate perceptions of prognosis, then treatment choices may not reflect each patient's true values., Objective: To test the hypothesis that among terminally ill cancer patients an accurate understanding of prognosis is associated with a preference for therapy that focuses on comfort over attempts at life extension., Design: Prospective cohort study., Setting: Five teaching hospitals in the United States., Patients: A total of 917 adults hospitalized with stage III or IV non-small cell lung cancer or colon cancer metastatic to liver in phases 1 and 2 of the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT)., Main Outcome Measures: Proportion of patients favoring life-extending therapy over therapy focusing on relief of pain and discomfort, patient and physician estimates of the probability of 6-month survival, and actual 6-month survival., Results: Patients who thought they were going to live for at least 6 months were more likely (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8-3.7) to favor life-extending therapy over comfort care compared with patients who thought there was at least a 10% chance that they would not live 6 months. This OR was highest (8.5; 95% CI, 3.0-24.0) among patients who estimated their 6-month survival probability at greater than 90% but whose physicians estimated it at 10% or less. Patients overestimated their chances of surviving 6 months, while physicians estimated prognosis quite accurately. Patients who preferred life-extending therapy were more likely to undergo aggressive treatment, but controlling for known prognostic factors, their 6-month survival was no better., Conclusions: Patients with metastatic colon and lung cancer overestimate their survival probabilities and these estimates may influence their preferences about medical therapies.

Context: An understanding of determinants of inconsistent pill-taking could be useful to service providers who are trying to help women prevent unwanted pregnancy. This article explores the predictors of inconsistent use in a nationally representative sample of U.S. women aged 15-44., Methods: Data on 1,485 pill users participating in the 1995 National Survey of Family Growth are used to describe users' characteristics, and logistic regression analyses are conducted to identify factors that predict inconsistent use (defined as missing two or more pills in a three-month period) among both users of the pill only and dual method users., Results: While 85% of pill users rely solely on the pill, 15% also use another method. Overall, 16% of users are inconsistent in their pill-taking (16% of those using the pill alone and 20% of dual method users). Among users of the pill only, Hispanic and non-Hispanic black women have a significantly increased likelihood of inconsistent use (odds ratios, 2.5 and 2.1, respectively), as do those who recently began use (2.7) and those who have had an unintended pregnancy (1.6). For dual method users, the odds are significantly elevated among women whose income is less than 250% of the federal poverty level (4.3) and among new users (4.5)., Conclusion: Service providers may need to better address consistency of pill-taking among women who have characteristics associated with inconsistent use.

The upsurge of large, single/multi-specialty group practices in contemporary health care has precipitated a corresponding surge in marketing strategies aimed at promoting group speed, efficiency, and/or productivity. Subsequently, the quality of care is often overlooked or redefined in financial terms. However, assessing quality of care--above and beyond strictly economic factors--can provide crucial information for executives concerned with making informed managerial decisions. This article explores one prototypical physician group's quest to assess their "quality care quotient," and explicates the process by which they obtained important data from patients, as well as how they used the assessment to improve their practice. The process may serve as an exemplar to physician groups concerned with conducting such analyses.

Objectives: This report shows data on a wide range of topics from the 1995 National Survey of Family Growth (NSFG), including: pregnancy and birth, marriage, divorce, cohabitation, sexual intercourse, contraception, infertility, use of family planning and other medical services, and health conditions and behavior., Methods: The data in this report are based on in-person interviews with a national sample of 10,847 women 15-44 years of age. The interviews lasted an average of 103 minutes. The response rate was 79 percent. The sample data are adjusted for nonresponse and are national estimates., Results: Following large increases in the 1970's and 1980's, the proportion of teenagers who have ever had sexual intercourse decreased slightly between 1990 and 1995; condom use, both at first intercourse and currently, has increased markedly since the 1970's. These changes may have contributed to the decreases in the teen birth rate observed in the 1990's. For all women 15-44 years of age, the number whose partner was currently using the condom (at the date of interview) increased from 3.6 million in 1982 to 5.1 million in 1988 and 7.9 million in 1995. About 8 percent of women reported that their first intercourse was not voluntary. This result is consistent with an earlier national survey. About 20 percent reported that they had been forced by a man to have intercourse at some time in their lives. About 10 percent of births in 1990-95 were unwanted by the mother compared with 12 percent in 1984-88. The decrease in unwanted births was particularly large for black women. It appears that the prevalence of pelvic inflammatory disease (PID) and vaginal douching have both decreased since 1988.

A survey of all 123 nonchronic-care pediatric hospitals in the United States revealed that 75% of hospitals responding had greatly increased the use of effective medical procedure preparation technologies, such as filmed modeling and coping skills instruction, in comparison to the last survey. Respondent characteristics such as position (e.g., nurse, child life worker, physician), degree (e.g., RN, MA, PhD), and length of time in the position failed to predict the type of techniques selected, but higher respondent knowledge and more psychological sources of preparation information did predict the use of preparation techniques used for drawing blood that experts rated as more effective. Challenges for more effective dissemination of research in the future are considered, as is the need for increased study of research-implementation links.

Within the last decade, a substantial amount of attention has been devoted to etiological research on the association between exposure to fallout radionuclides from the Chernobyl accident and radiation-induced late effects (cancer) among children. A majority of the studies completed to date have been of the descriptive type, which only correlate average population exposure with average rate of cancer incidence as a function of calendar period. Since individual dosimetry is not performed in descriptive studies, it is unclear whether exposure precedes the development of cancer and a final decision cannot be made regarding the association between radiation exposure and cancer. This paper reviews the background epidemiology and outlines an analytical study design that is needed to clarify the unclear association between Chernobyl fallout exposure and childhood cancer. We discuss the essential elements of an analytical case-control design such as genetic predisposition, vital statistics, sample size and power determinations, ascertainment of cases and controls, and phenomenological dose modeling to establish individual doses. Examples such as cytogenetic biodosimetry, medical radiation dosimetry, and cytogenetic characterization of leukemia to minimize exposure and diagnostic misclassification are provided. We recommend the analytical methods described in this paper for studying the role of Chernobyl radionuclides and development of childhood cancer.