Clinical research presents health care providers with information on the natural history and clinical presentations of disease as well as diagnostic and treatment options. Consumers, patients, and caregivers also require this information to decide how to evaluate and treat their conditions. All too often, the information necessary to inform these medical decisions is incomplete or unavailable, resulting in more than half of the treatments delivered today lacking clear evidence of effectiveness.

Comparative effectiveness research (CER) identifies what works best for which patients under what circumstances. Congress, in the American Recovery and Reinvestment Act (ARRA) of 2009, tasked the Institute of Medicine (IOM) to recommend national priorities for research questions to be addressed by CER and supported by ARRA funds. In its 2009 report, Initial National Priorities for Comparative Effectiveness Research, the authoring committee establishes a working definition of CER, develops a priority list of research topics to be undertaken with ARRA funding using broad stakeholder input, and identifies the necessary requirements to support a robust and sustainable CER enterprise. The full list of priorities and recommendations can be found in the below report brief.

BACKGROUND: Women are at higher risk than men for adverse events with certain invasive cardiac procedures. Our objective was to compare rates of in-hospital adverse events in men and women receiving implantable cardioverter- defibrillator (ICD) therapy in community practice.

METHODS AND RESULTS: Using the National Cardiovascular Data Registry ICD Registry, we identified patients undergoing first-time ICD implantation between January 2006 and December 2007. Outcomes included in-hospital adverse events after ICD implantation. Multivariable analysis assessed the association between gender and in-hospital adverse events, with adjustment for demographic, clinical, procedural, physician, and hospital characteristics. Of 161,470 patients, 73% were male, and 27% were female. Women were more likely to have a history of heart failure (81% versus 77%, P<0.01), worse New York Heart Association functional status (57% versus 50% in class III and IV, P<0.01), and nonischemic cardiomyopathy (44% versus 27%, P<0.01) and were more likely to receive biventricular ICDs (39% versus 34%, P<0.01). In unadjusted analyses, women were more likely to experience any adverse event (4.4% versus 3.3%, P<0.001) and major adverse events (2.0% versus 1.1%, P<0.001). In multivariable models, women had a significantly higher risk of any adverse event (OR 1.32, 95% CI 1.24 to 1.39) and major adverse events (OR 1.71, 95% CI 1.57 to 1.86).

CONCLUSIONS: Women are more likely than men to have in-hospital adverse events related to ICD implantation. Efforts are needed to understand the reasons for higher ICD implantation-related adverse event rates in women and to develop strategies to reduce the risk of these events.

Any close examination of the epidemiologic trends in childhood suggests 2 fundamental findings. First, pediatrics has been among the most successful specialties in the history of medicine. Second, pediatrics must change. At the heart of this seeming paradox is the recognition that pediatrics has so altered the clinical threats to the well-being ofthe past 50 years that new structures of care will be required. The pride in pediatrics' remarkable record of impact and at the same time defend the status quo. modern children over epidemiology presents a ruthless logic: one cannot take

The challenge to the pediatrics community is to ensure that the changes that will inevitably come are exquisitely focused on meeting the needs of children. We must craft strategies that can protect what remains essential in pediatric practice and yet embrace a historic opportunity to craft requisite reforms. It is in this context that the recent initiatives by the American Board of Pediatrics [Editor's note: also see related supplement titled "Residency Review and Redesign in Pediatrics: New (and Old) Questions" with this issue of Pediatrics.] and the American Academy of Pediatrics to consider new training and practice needs should be welcomed. However, the nature and scale of the challenge will require a new level of direct engagement from pediatricians and a renewed progressive commitment to speak with a stronger and more coherent collective voice.

ABSTRACT

OBJECTIVE. Despite the success of current newborn screening programs, some critics have argued that in the 1960s hundreds of children with false-positive results for phenylketonuria suffered death or disability from treatment with restrictive diets. Medically adverse outcomes after false-positive results may be a reason to be cautious when expanding current newborn screening programs. We sought to determine if newborn screening programs for phenylketonuria before 1980 led to adverse medical outcomes in children with false-positive results.

PATIENTS AND METHODS. We examined the history of newborn screening programs for phenylketonuria in the United States. We reviewed the historical scholarship, conducted a systematic search for medical adverse outcomes, and interviewed key participants in the history of newborn screening programs.

RESULTS. We found no population-based studies of early screening programs for phenylketonuria. One author reported 2 infants treated with restrictive diets after false-positive results for phenylketonuria who were developmentally delayed, and there is unpublished evidence of 4 additional cases of inappropriate treatment, although adverse outcomes were not documented. There were also 4 published reports of adverse medical outcomes after treating children with phenylketonuria variants, as screening for phenylketonuria revealed infants with intermediate or transiently high levels of phenylalanine.

CONCLUSIONS. We found little evidence of death or disability that resulted from the inappropriate treatment of well children who were falsely identified by early newborn screening programs. Because the first decade of newborn screening typically reveals diagnostic and therapeutic complexity, systematic follow-up of screened populations and rapid dissemination of results may reduce morbidity/mortality rates.

PRIMARY AIM: Examine the effectiveness of extended cognitive behavior therapy (CBT) in promoting longer-term smoking abstinence.

DESIGN: Open-label treatment phase followed by extended treatment phase. Randomization conducted prior to entry into open-label treatment phase; analysis based on intention-to-treat to avoid threat of selection bias.

SETTING: Community smoking cessation clinic.

PARTICIPANTS: A total of 304 adult smokers (> or = 18 years of age; > or = 10 cigarettes/day). INTERVENTION: Open-label (8 weeks): all participants received bupropion SR, nicotine patch, CBT. Extended treatment (12 weeks): participants received either CBT + voicemail monitoring and telephone counseling or telephone-based general support.

MEASUREMENTS: Seven-day point prevalence abstinence, expired-air carbon monoxide. RESULTS: At week 20 follow-up, CBT produced a higher 7-day point prevalence abstinence rate: 45% versus 29%, P = 0.006; at 52 weeks the difference in abstinence rates (31% versus 27%) was not significant. History of depression was a moderator of treatment. Those with a positive history had a better treatment response at 20 weeks when assigned to the less intensive telephone support therapy (P < 0.05).

CONCLUSION: The superiority of CBT to 20 weeks suggests that continued emphasis on the development of cognitive and behavioral strategies for maintaining non-smoking during an extended treatment phase may help smokers to maintain abstinence in the longer term. At present, the minimum duration of therapy is unknown.

Women's choices appear to emphasize child welfare more than those of men. This paper presents new evidence on how suffrage rights for American women helped children to benefit from the scientific breakthroughs of the bacteriological revolution. Consistent with standard models of electoral competition, suffrage laws were followed by immediate shifts in legislative behavior and large, sudden increases in local public health spending. This growth in public health spending fueled large-scale door-to-door hygiene campaigns, and child mortality declined by 8-15 percent (or 20,000 annual child deaths nationwide) as cause-specific reductions occurred exclusively among infectious childhood killers sensitive to hygienic conditions.

Introduction: Little is known about the natural history of malignant solitary pulmonary nodules (SPN). Experts' beliefs may help fill these knowledge gaps and explain variation in clinical practices.

Methods: Using a modified Delphi process, we surveyed a group of lung cancer experts about tumor growth, disease progression, and prognosis in patients with malignant SPN. After completing the first survey, experts were given the opportunity during a second survey to revise their responses in light of their peers' beliefs.

Results: The response rate was 100% (14 of 14) for both surveys. There was consensus that disease progression depends on the tumor growth rate, that survival for patients with untreated lung cancer is approximated by a declining exponential function, and that treatment is delayed by approximately 1 tumor volume doubling time (TVDT) in patients who undergo a period of watchful waiting. Just over half of experts (8 of 14) agreed that lung cancer progresses in three steps (from local to regional to distant disease), whereas 43% (6 of 14) preferred a 2-step model (from local to systemic disease). Likewise, 64% of experts (9 of 14) believed that malignant nodules grow exponentially, whereas 36% (5 of 14) believed that growth is slower than exponential. Experts' estimates of the risk of disease progression during a period of observation lasting 1 TVDT varied from 1 to 50%. Estimates of 5-year survival for patients in whom diagnosis and treatment were delayed by 1 TVDT varied between 40% and 80%.

Conclusions: There is substantial variability in experts' beliefs about the natural history of untreated, malignant SPN. Different beliefs may be partly responsible for variation in management practices.

Context: Studies of prostitution have focused largely on individuals involved in the commercial sex trade, with an emphasis on understanding the public health effect of this behavior. However, a broader understanding of how prostitution affects mental and physical health is needed. In particular, the study of prostitution among individuals in substance use treatment would improve efforts to provide comprehensive treatment. Objectives: To document the prevalence of prostitution among women and men entering substance use treatment, and to test the association between prostitution, physical and mental health, and health care utilization while adjusting for reported history of childhood sexual abuse, a known correlate of prostitution and poor health outcomes.

Design, Setting, and Participants: Cross-sectional, secondary data analysis of 1606 women and 3001 men entering substance use treatment in the United States who completed a semistructured intake interview as part of a larger study. Main Outcome

Measures: Self-reported physical health (respiratory, circulatory, neurological, and internal organ conditions, bloodborne infections) and mental health (depression, anxiety, psychotic symptoms, and suicidal behavior), and use of emergency department, clinic, hospital, or inpatient mental health services within the past year.

Results: Many participants reported prostitution in their lifetime (50.8% of women and 18.5% of men) and in the past year (41.4% of women and 11.2% of men). Prostitution was associated with increased risk for bloodborne viral infections, sexually transmitted diseases, and mental health symptoms. Prostitution was associated with use of emergency care in women and use of inpatient mental health services for men.

Conclusions: Prostitution was common among a sample of individuals entering substance use treatment in the United States and was associated with higher risk of physical and mental health problems. Increased efforts toward understanding prostitution among patients in substance use treatment are warranted. Screening for prostitution in substance use treatment could allow for more comprehensive care to this population.