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Background: Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are potentially chemopreventive.Objective: We examined the relation between NSAID use and nonmelanoma skin cancer in a population-based case-control study.Methods: NSAID and analgesic use was analyzed in 1484 participants: 535 with squamous cell carcinoma (SCC), 487 with basal cell carcinoma (BCC), and 462 control subjects.Results: Use of NSAIDs, particularly aspirin, was associated with a reduced odds ratio (OR) of SCC, especially tumors positive for p53 (OR 0.29; 95% confidence interval 0.11-0.79) or with PTCH loss of heterozygosity (OR 0.35; 95% confidence interval 0.13-0.96). Although not considered a NSAID, decreased ORs of both basal cell carcinoma and SCC were observed in relation to use of paracetamol (acetaminophen). Risk of BCC was unrelated to NSAID use.Limitations: Self-reported drug use was a limitation.Conclusions: This study supports the hypothesis that NSAIDs, aspirin in particular, may reduce risk of SCC and may affect specific molecular subtypes of SCC. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD), a largely preventable and manageable respiratory condition, affects an estimated 12% to 20% of adults. Long-acting inhaled [beta]-agonists and anticholinergics have both been shown to improve COPD outcomes and are recommended for moderate to severe disease; however, little is known about their comparative effectiveness. Objective: To compare survival in older patients with COPD who initially receive inhaled long-acting [beta]-agonists with that of patients who receive anticholinergics. Design: Population-based, retrospective cohort study. Setting: Ontario, Canada. Patients: Patients aged 66 years or older (who carry the largest burden of COPD and for whom data were available) who met a validated case definition of COPD on the basis of health administrative data and were newly prescribed an inhaled long-acting [beta]-agonist or a long-acting anticholinergic (but not both) between 2003 and 2007. Patients were followed for up to 5.5 years. Measurements: The primary outcome was all-cause mortality. Results: A total of 46 403 patients with COPD (mean age, 77 years; 49% women) were included. Overall mortality was 38.2%. Mortality was higher in patients initially prescribed a long-acting anticholinergic than in those initially prescribed a long-acting inhaled [beta]-agonist (adjusted hazard ratio, 1.14 [95% CI, 1.09 to 1.19]). Rates of hospitalizations and emergency department visits were also higher in those initially prescribed a long-acting anticholinergic. Limitation: Patients were classified as having COPD on the basis of health administrative records, which did not contain information about lung function. Conclusion: Older adults initially prescribed long-acting inhaled [beta]-agonists for the management of moderate COPD seem to have lower mortality than those initially prescribed long-acting anticholinergics. Further research is needed to confirm these findings in younger patients and in a randomized, controlled trial. Primary Funding Source: Government of Ontario, Canada. [ABSTRACT FROM AUTHOR]

Background: Human evidence that ionizing radiation is carcinogenic first came from reports of nonmelanoma skin cancers (NMSCs) on the hands of workers using early radiation devices. An increased risk of NMSC has been observed among uranium miners, radiologists, and individuals treated with x rays in childhood for tinea capitis (ringworm of the scalp) or for thymic enlargement; NMSC is one of the cancers most strongly associated with the atomic bombing of Hiroshima and Nagasaki. Although exposure to ionizing radiation is a known cause of NMSC, it is not yet clear whether therapeutic radiation causes both major histologic types of NMSC, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Additionally, the potentially modifying effects, such as latency, age when treated, and type of treatment, are not well understood.Purpose: We investigated the relative risks of BCC and SCC associated with previous radiation therapy and evaluated these risks in relation to age and time since initial treatment and the medical condition for which radiation therapy was given.Methods: The study group comprised individual diagnosed with at least one BCC or SCC from January 1980 through February 1986, who were recruited to participate in a skin cancer prevention trial designed to test whether oral beta-carotene supplementation would reduce the risk of new NMSCs. Patients were identified through the dermatology and pathology records of academic medical centers in Hanover, NH; Los Angeles, CA; San Francisco, CA; and Minneapolis, MN. Each participant completed a questionnaire detailing lifetime residence, pigmentary characteristics, occupational and recreational sun exposure, and history of radiation therapy. At enrollment, a study dermatologist assessed skin type (tendency to burn or tan) and extent of actinic skin damage. Participants were followed with an annual dermatologic examination for an average of 4 years. Of the 5232 potentially eligible individuals, 1805 were enrolled in the trial. We excluded 112 patients who reported previous radiation therapy for skin cancer only and three with missing information on whether they were ever treated with radiation therapy, leaving 1690 patients for the analysis. Approximately 4% of the patients died or discontinued participation for other reasons during each study year. We examined time to occurrence of first new histopathologically confirmed BCC and SCC during the follow-up period in relation to history of radiation therapy (for reasons other than NMSC) using a proportional hazards model. A multiple end points survival model was used to compare the rate ratios (RRs) for BCC and SCC. We also used a longitudinal method of analysis to compute the RR of total new BCC and SCC tumors per person per study year associated with radiation therapy. Using this method, we additionally assessed the potential modifying effects of age at treatment, latency, and type of therapy. All P values were derived from two-sided statistical tests of significance.Results: Among the participants we studied, 597 developed a new BCC (n = 1553 tumors) and 118 developed a new SCC (n = 179 tumors). The time to first new BCC, but not SCC, was associated with prior radiation therapy (RR = 1.7; 95% confidence interval [CI] = 1.4-2.0 and RR = 1.0; 95% CI = 0.6-1.7, respectively; P = .03 for the difference between the RRs). The RR of total BCC tumors was slightly higher (RR = 2.3; 95% CI = 1.7-3.1), but it was still unity for SCC (RR = 1.0; 95% CI = 0.5-1.9). BCC risk appeared to increase with younger age at exposure and time since initially treated, although these effects were only marginally statistically significant (P for trend = .06 and .07, respectively). Also, risk of BCC was more strongly related to treatment for acne (RR = 3.3; 95% CI = 2.1-5.2) than other conditions.Conclusions and Implications: Our data suggest that exposure to therapeutic radiation is associated with BCC but not with SCC. [ABSTRACT FROM AUTHOR]

The relationship of trauma history to physical and emotional functioning in primary care pain patients was examined. Data were drawn from a mailed screening questionnaire for a larger study designed to evaluate an intervention for improving pain management in primary care. Results indicated that 50.4% of the pain patients reported experiencing at least one previous emotionally traumatic event. Further, 31% of patients with trauma history continued to be bothered by that experience. Finally, patients who continued to be significantly bothered by the trauma reported more pain, emotional distress, poorer social functioning, and more difficulty with engaging in their daily activities than did patients with either no trauma history or who had a trauma history but did not have bothersome thoughts of the trauma. These preliminary findings suggest that the experience of trauma alone was not related to additional impairments in physical and psychosocial functioning. However, the report that one continued to be bothered by thoughts of a trauma was associated with greater impairments in functioning. [ABSTRACT FROM AUTHOR]

Introduction: Information on newborn gestational age (GA) is essential in research on perinatal and infant health, but it is not always available from administrative databases. We developed and validated a GA prediction model for singleton births for use in epidemiological studies., Methods: Derivation of estimated GA was calculated based on 130 328 newborn infants born in Ontario hospitals between 2007 and 2009, using linear regression analysis, with several infant and maternal characteristics as the predictor (independent) variables. The model was validated in a separate sample of 130 329 newborns., Results: The discriminative ability of the linear model based on infant birth weight and sex was reasonably approximate for infants born before the 37th week of gestation (r2 = 0.67; 95% CI: 0.65-0.68), but not for term births (37-42 weeks; r2 = 0.12; 95% CI: 0.12-0.13). Adding other infant and maternal characteristics did not improve the model discrimination., Conclusion: Newborn gestational age before 37 weeks can be reasonably approximated using locally available data on birth weight and sex.

Objective: Despite marked growth in neonatal intensive care during the past 30 years, it is not known if neonatologists and beds are preferentially located in regions with greater newborn risk. This study reports the relationship between regional measures of intensive care capacity and low birth weight infants using newly developed market-based regions of neonatal intensive care., Design: Cross-sectional small-area analysis of 246 neonatal intensive care regions (NICRs)., Data Sources: 1996 American Medical Association and American Osteopathic Association masterfiles data of clinically active neonatologists; 1999 American Academy of Pediatrics Section on Perinatal Pediatrics survey of directors of neonatal intensive care units in the United States with 100% response rate; 1995 linked birth/death data., Results: The number of total births per neonatologist across NICRs ranged from 390 to 8197 (median: 1722) and the number of total births per intensive care bed ranged from 72 to 1319 (median: 317). The associations between capacity measures and low birth weight rates across NICRs were statistically significant but negligible (R(2): 0.04 for neonatologists; 0.05 for beds). NICRs in the quintile with the greatest neonatologist capacity (average of only 863 births per neonatologist) had very low birth weight (VLBW) rates of 1.5% while those in the quintile of lowest neonatologist capacity (average of 3718 births per neonatologist) had VLBW rates of 1.3%; a similar lack of meaningful difference in VLBW rates was noted across quintiles of intensive care bed capacity. Including midlevel providers and intermediate care beds to the analyses did not alter the findings., Conclusions: Neonatal intensive care capacity is not preferentially located in regions with greater newborn need as measured by low birth weight rates. Whether greater capacity affords benefits to the newborns remains unknown.

Epidemiologic studies of disease often produce inconclusive or contradictory results due to small sample sizes or regional variations in the disease incidence or the exposures. To clarify these issues, researchers occasionally pool and reanalyse original data from several large studies. In this paper we explore the use of a two-stage random-effects model for analysing pooled case-control studies and undertake a thorough examination of bias in the pooled estimator under various conditions. The two-stage model analyses each study using the model appropriate to the design with study-specific confounders, and combines the individual study-specific adjusted log-odds ratios using a linear mixed-effects model; it is computationally simple and can incorporate study-level covariates and random effects. Simulations indicate that when the individual studies are large, two-stage methods produce nearly unbiased exposure estimates and standard errors of the exposure estimates from a generalized linear mixed model. By contrast, joint fixed-effects logistic regression produces attenuated exposure estimates and underestimates the standard error when heterogeneity is present. While bias in the pooled regression coefficient increases with interstudy heterogeneity for both models, it is much smaller using the two-stage model. In pooled analyses, where covariates may not be uniformly defined and coded across studies, and occasionally not measured in all studies, a joint model is often not feasible. The two-stage method is shown to be a simple, valid and practical method for the analysis of pooled binary data. The results are applied to a study of reproductive history and cutaneous melanoma risk in women using data from ten large case-control studies., (Copyright 2001 John Wiley & Sons, Ltd.)

Context: In the past 30 years, the number of neonatologists has increased while total births have remained nearly constant. It is not known how equitably this expanded workforce is distributed., Objective: To determine the geographic distribution of neonatologists in the United States., Data Sources: 1996 American Medical Association physician masterfiles; 1999 survey of all U.S. neonatal intensive care units; 1995 American Hospital Association hospital survey; and 1995 U.S. vital records., Measures: The number of neonatologists and neonatal mid-level providers per live birth within 246 market-based regions., Results: The neonatology workforce varied substantially across neonatal intensive care regions. The number of neonatologists per 10,000 live births ranged from 1.2 to 25.6 with an interquintile range of 3.5 to 8.5. The weakly positive correlation between neonatologists and neonatal mid-level providers per live birth is not consistent with substitution of neonatal mid-level providers for neonatologists (Spearman rank-correlation coefficient, 0.17; P < 0.01). There was no difference in the percentage of neonatal fellows in the lowest and highest workforce quintile (14% vs. 16%) or in the percentage of neonatologists engaged predominantly in research, teaching, or administration (14% in lowest and highest quintiles)., Conclusions: The regional supply of neonatologists varies dramatically and cannot be explained by the substitution of neonatal mid-level providers or by the presence of academic medical centers. Further research is warranted to understand whether neonatal intensive care resources are located in accordance with risk and whether more resources improve newborn outcomes.

Arsenic is a known carcinogen specifically linked to skin cancer occurrence in regions with highly contaminated drinking water or in individuals who took arsenic-containing medicines. Presently, it is unknown whether such effects occur at environmental levels found in the United States. To address this question, the authors used data collected on 587 basal cell and 284 squamous cell skin cancer cases and 524 controls interviewed as part of a case-control study conducted in New Hampshire between 1993 and 1996. Arsenic was determined in toenail clippings using instrumental neutron activation analysis. The odds ratios for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were close to unity in all but the highest category. Among individuals with toenail arsenic concentrations above the 97th percentile, the adjusted odds ratios were 2.07 (95% confidence interval (CI): 0.92, 4.66) for SCC and 1.44 (95% CI: 0.74, 2.81) for BCC, compared with those with concentrations at or below the median. While the risks of SCC and BCC did not appear elevated at the toenail arsenic concentrations detected in most study subjects, the authors cannot exclude the possibility of a dose-related increase at the highest levels of exposure experienced in the New Hampshire population.

Objective: To estimate the relative risk of developing basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) after receiving therapeutic ionizing radiation., Design: Population-based case-control study., Setting: New Hampshire., Patients: A total of 592 cases of BCC and 289 cases of SCC identified through a statewide surveillance system and 536 age- and sex-matched controls selected from population lists., Main Outcome Measures: Histologically confirmed BCC and invasive SCC diagnosed between July 1, 1993, through June 30, 1995, among New Hampshire residents., Results: Information regarding radiotherapy and other factors was obtained through personal interviews. An attempt was made to review the radiation treatment records of subjects who reported a history of radiotherapy. Overall, an increased risk of both BCC and SCC was found in relation to therapeutic ionizing radiation. Elevated risks were confined to the site of radiation exposure (BCC odds ratio, 3. 30; 95% confidence interval, 1.60-6.81; SCC odds ratio, 2.94; 95% confidence interval, 1.30-6.67) and were most pronounced for those irradiated for acne exposure. For SCC, an association with radiotherapy was observed only among those whose skin was likely to sunburn with sun exposure., Conclusions: These results largely agree with those of previous studies on the risk of BCC in relation to ionizing radiation exposure. In addition, they suggest that the risk of SCC may be increased by radiotherapy, especially in individuals prone to sunburn with sun exposure. Arch Dermatol. 2000;136:1007-1011

Objective: To explore whether geographic variations in Medicare hospital utilization rates are due to differences in local hospital capacity, after controlling for socioeconomic status and disease burden, and to determine whether greater hospital capacity is associated with lower Medicare mortality rates., Data Sources/study Setting: The study population: a 20 percent sample of 1989 Medicare enrollees. Measures of resources were based on a national small area analysis of 313 Hospital Referral Regions (HRR). Demographic and socioeconomic data were obtained from the 1990 U.S. Census. Measures of local disease burden were developed using Medicare claims files., Study Design: The study was a cross-sectional analysis of the relationship between per capita measures of hospital resources in each region and hospital utilization and mortality rates among Medicare enrollees. Regression techniques were used to control for differences in sociodemographic characteristics and disease burden across areas., Data Collection/extraction Methods: Data on the study population were obtained from Medicare enrollment (Denominator File) and hospital claims files (MedPAR) and U.S. Census files., Principal Findings: The per capita supply of hospital beds varied by more than twofold across U.S. regions. Residents of areas with more beds were up to 30 percent more likely to be hospitalized, controlling for ecologic measures of socioeconomic characteristics and disease burden. A greater proportion of the population was hospitalized at least once during the year in areas with more beds; death was also more likely to take place in an inpatient setting. All effects were consistent across racial and income groups. Residence in areas with greater levels of hospital resources was not associated with a decreased risk of death., Conclusions: Residence in areas of greater hospital capacity is associated with substantially increased use of the hospital, even after controlling for socioeconomic characteristics and illness burden. This increased use provides no detectable mortality benefit.

Objective: Despite national initiatives to improve asthma medical treatment, the appropriateness of physician prescribing for children with asthma remains unknown. This study measures trends and recent patterns in the pediatric use of medications approved for reversible obstructive airway disease (asthma medications)., Design: Population-based longitudinal and cross-sectional analyses. Setting. A nonprofit staff model health maintenance organization located in the Puget Sound area of Washington state., Participants: Children 0 to 17 years of age enrolled continuously during any one of the years from 1984 to 1993 (N = 83 232 in 1993). PRIMARY OUTCOME MEASURES. Percent of enrollees filling prescriptions for asthma medications and fill rates by medication class and estimated duration of inhaled antiinflammatory medication use., Results: Between 1984 and 1993, the frequency of asthma medication use increased: the percent of children filling any asthma medication prescription increased from 4. 0% to 8.1%, whereas the percent filling an inhaled antiinflammatory inhaler rose from 0.4% to 2.4%. In contrast, the intensity of inhaled antiinflammatory use decreased among users; 37% of users filled more than two inhalers during the year in 1984, and 29% in 1993. In high beta-agonist users (filling more than two beta-agonist inhalers each quarter per year), the estimated duration of inhaled antiinflammatory use increased slightly from a mean of 4.1 months per year in 1984-1986 to 5.0 months in 1991-1993; estimated duration of use in adolescents 10 to 17 years of age was approximately half that of children 5 to 9 years of age., Conclusions: The proportion of children using asthma medications increased substantially during the study period, but the use of inhaled antiinflammatory medication per patient remained low even for those using large amounts of inhaled beta-agonists. These findings suggest that most asthma medications were used by children with mild lower airway symptoms and that inhaled antiinflammatory medication use in children with more severe disease fell short of national guidelines.

We conducted a study to estimate the current incidence rates of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) of the skin in the population of New Hampshire (NH), USA, and to quantify recent changes in the incidence rates of these malignancies. BCCs and SCCs diagnosed among NH residents were identified through physician practices and central pathology laboratories in NH and bordering regions from June 1979 through May 1980 and from July 1993 through June 1994. For each diagnosis period, we estimated the age-adjusted incidence rates for both BCC and SCC among both men and women and for separate anatomic sites. Between 1979-1980 and 1993-1994, incidence rates of SCC increased by 235% in men and by 350% in women. Incidence rates of BCC increased by more than 80% in both men and women. While the absolute increase was greatest for tumors of the head and neck, the relative change was most pronounced for tumors on the trunk in men and on the lower limb in women. Thus, there has been a marked rise in the incidence rates of BCC and SCC skin cancers in NH in recent years. The anatomic pattern of increase in BCC and SCC incidence is consistent with an effect of greater sunlight exposure. Studies of BCC and SCC occurrence are needed to identify possible behavioral and environmental factors and to assess possible changes in diagnostic practices that might account for the rise in incidence of these common malignancies.

Objective: Because of time constraints in the office environment, problems of concern to elderly patients may not be raised during clinic visits. To facilitate communication about geriatric health problems, we examined the impact of a strategy that used patient self-assessment data to improve community practices., Design: Twenty-two primary care practices were randomized to participate in the intervention strategy (intervention practices) or to provide usual care (usual care practices)., Setting: Primary care practices in 16 towns in New Hampshire (total, 45 physicians)., Patients: 1651 patients 70 years of age or older., Intervention: All patients received a mailed survey that asked about their health problems and about how well these problems were being addressed by their physicians. In the intervention practices, these data were used to generate a customized letter that directed the patient to specific sections in an 80-page modified version of the National Institute on Aging's Age Pages and were summarized and communicated to the patient's physician., Main Outcome Measure: Change from baseline in patients' overall assessment of health care., Results: In 8 of 11 intervention practices, patients felt that their care had improved over the 2-year study period. This improvement occurred in only 1 of 11 usual care practices (P = 0.003). Patients in intervention practices reported receiving significantly more help with physical function, fall prevention, and assistance for memory problems. Self-assessed health status did not differ in the two groups., Conclusion: A standard, easy-to-implement strategy to improve the quality of provider--patient interactions can improve the satisfaction of older patients cared for in community practices.

Objective: Asthma hospitalization rates continue to increase nationally for children despite efforts by the National Institutes of Health and specialty organizations to improve outcomes through the dissemination of practice guidelines. To understand the generalizability of national trends to regional populations, we studied childhood hospitalizations over a 10-year period in four northeastern states., Design: Longitudinal analysis of hospitalization rates by patient residence and patient characteristics using state hospital discharge datasets., Population: Age < 18 years residing in Maine, New Hampshire, Vermont, or New York state during the period 1985 to 1994., Results: In multivariate analyses (controlling for age, sex, race/ethnicity, median household income, metropolitan status), we found that New York asthma hospitalization rates increased 3.8% per annum (95% confidence interval: 3.3, 4.2), whereas in New Hampshire, rates decreased 5.8% (95% confidence interval: 7.6, 4.1). Maine and Vermont rates did not change significantly during the study period. Increased asthma hospitalization rates were noted in black and Hispanic populations, in children residing in zip codes with lower median household incomes, and in those living in metropolitan areas. Hospitalization rates for nonasthma causes fell substantially. As a result, the proportion of hospital days attributed to childhood asthma increased in all population groups., Conclusions: Asthma discharge rates measured by the state of residence or socioeconomic characteristic do not necessarily parallel national trends. None of the current hypotheses offered to explain national trends in asthma hospitalization rates (changes in disease severity, diagnostic substitution, or differences in the supply and character of medical care) can be the sole explanation of these regional trends. Efforts intended to improve asthma outcomes may benefit a greater number of children by redirecting resources toward specific populations identified through state hospital discharge datasets.

We extend the linear random-effects growth curve model (REGCM) (Laird and Ware, 1982, Biometrics 38, 963-974) to study the effects of population covariates on one or more characteristics of the growth curve when the characteristics are expressed as linear combinations of the growth curve parameters. This definition includes the actual growth curve parameters (the usual model) or any subset of these parameters. Such an analysis would be cumbersome using standard growth curve methods because it would require reparameterization of the original growth curve. We implement a two-stage method of estimation based on the two-stage growth curve model used to describe the response. The resulting generalized least squares (GLS) estimator for the population parameters is consistent, asymptotically efficient, and multivariate normal when the number of individuals is large. It is also robust to model misspecification in terms of bias and efficiency of the parameter estimates compared to maximum likelihood with the usual REGCM. We apply the method to a study of factors affecting the growth rate of salmonellae in a cubic growth model, a characteristic that cannot be analyzed easily using standard techniques.

Objective: To assess the impact of regional supplemented general anesthesia (RSGEN) on regional myocardial function during abdominal aortic surgery (AAS)., Design: Prospective randomized study., Setting: Single academic medical center., Participants: Seventy-three patients scheduled for infrarenal aortic aneursymectomy., Interventions: Patients received standardized intraoperative anesthetic management consisting of either general anesthesia (GA; n = 37) or general anesthesia supplemented by epidural anesthesia (RSGEN; n = 36)., Measurements and Main Results: Hemodynamic measurements and transesophageal echocardiograms (TEE) were obtained at eight intraoperative times. The electrocardiogram (ECG) was continuously recorded using Holter monitoring. Of the 56 patients with interpretable TEE recordings, 8 of 30 (27%) GA patients and 7 of 26 (27%) RSGEN patients developed new segmental wall motion abnormalities (SWMAs). There was no treatment effect on either the incidence (p = 0.23) or the intensity (p = 0.34) of SWMAs. Cross-clamping of the aorta was associated with the onset of new SWMAs (odds ratio, 8.2; 95% CI, 1.1 to 64; p = 0.04). Among the 63 patients with interpretable Holter recordings, 9 of 34 (26%) GA patients and 9 of 29 (31%) RSGEN patients exhibited intraoperative ischemia. There was no treatment effect on the incidence (p = 0.22) or intensity (p = 0.67) of ECG ischemia., Conclusion: Despite providing modest hemodynamic depression, RSGEN did not reduce the incidence or intensity of either regional myocardial dysfunction or ECG ischemia. New SWMAs were temporally associated with cross-clamping of the aorta and tended to resolve with unclamping.

Purpose: The purpose of this study was to assess the effect of superficial femoral artery (SFA) stenosis morphologic characteristics and lesion location on the rate of atherosclerotic disease progression., Methods: We identified 19 patients who required arteriography for treatment of critical leg ischemia and who had previously undergone arteriography of that leg when minimal or no symptoms were present. These initial incidental arteriographic evaluations were performed during evaluation of arterial disease in another vascular bed from 4 to 81 months (mean, 32 months) previously. Distinct SFA stenoses or occlusion on the final arteriogram (n = 98) were characterized by their location, length, stenosis severity, and morphologic appearance on the initial arteriogram. The contribution of patient-specific risk factors to disease progression was also assessed., Results: Stenosis progression occurred independently among multiple lesions within the same patient (negligible intraclass correlation coefficient, r = 0.06). Lesions in the adductor canal region were more likely to occlude than lesions elsewhere in the SFA (adjusted odds ratio = 10.7; p = 0.03). Severity of initial lesion stenosis also was predictive of occlusion (adjusted odds ratio = 1.8; p = 0.04). However, most progressing lesions (93%) actually arose in areas of initially mild disease (stenoses < 50%) despite more severe initial lesions elsewhere. Increasing age (p = 0.023) and previous contralateral leg bypass (p = 0.036) were also associated with increasing rates of lesion progression. Smooth-asymmetric lesions progressed 11% more slowly than other lesion types (p = 0.003)., Conclusions: Our analysis of atherosclerotic SFA lesion progression in patients with critical ischemia shows that initial stenosis severity was associated with higher occlusion rates and that smooth-asymmetric lesions progressed more slowly than lesions with other morphologic characteristics. Severe stenoses usually arose from minimally diseased regions and progressed more rapidly than preexisting, more highly stenotic lesions. Most SFA occlusions resulted from disease progression in the adductor canal region whether or not antecedent lesions were seen on arteriography and whether or not more severe stenoses were initially present elsewhere. Increased age and history of previous contralateral bypass were patient-specific predictors of lesion progression.

We conducted a nested case-control study of squamous cell skin cancer (SCC) to determine whether risk was related to plasma concentrations of selenium, alpha-tocopherol, beta-carotene, and retinol. We derived the study sample from participants in our Skin Cancer Prevention Study, all of whom had at least one basal cell or squamous cell skin cancer before study entry. Those who developed a new squamous cell skin cancer during the 3-5-year follow-up period were selected as cases (n = 132). Controls (n = 264) were chosen at random, with matching by age, sex, and study center, from among those who did not develop SCC but were being followed actively at the time the SCC case was diagnosed. Prediagnostic plasma samples were analyzed for alpha-tocopherol, beta-carotene, and retinol using high-performance liquid chromatography. Selenium determinations were made using instrumental neutron activation analysis. Odds ratios were computed using conditional logistic regression for matched samples. We found no consistent pattern of SCC risk associated with any of the nutrients examined. The odds ratios (95% confidence intervals) for the highest versus the lowest quartiles of beta-carotene, retinol, alpha-tocopherol, and selenium were 0.73 (0.38-1.41), 1.43 (0.77-2.64), 0.89 (0.43-1.85), and 0.86 (0.47-1.58), respectively. Thus, our data add to the growing body of evidence that these nutrients, at the concentrations we evaluated, are not related strongly to SCC risk.

Objective: To examine the relationship between beta carotene plasma concentration and beta carotene supplementation and risk of death from major disease causes., Design: Cohort study of plasma concentrations; randomized, controlled clinical trial of supplementation., Setting: Medical school-affiliated dermatology practices., Patients: A total of 1188 men and 532 women with mean age of 63.2 years, who had enrolled in a randomized clinical trial of beta carotene supplementation to prevent nonmelanoma skin cancer., Intervention: Oral beta carotene, 50 mg per day for a median of 4.3 years., Main Outcome Measures: All-cause mortality and mortality from cardiovascular disease and cancer., Results: During a median follow-up period of 8.2 years, there were 285 deaths. Persons whose initial plasma beta carotene concentrations were in the highest quartile (>0.52 micromol/L [27.7 microg/dL]) had a lower risk of death from all causes (adjusted relative rate [RR], 0.52; 95% confidence interval [CI] 0.44 to 0.87) and from cardiovascular diseases (adjusted RR, 0.57; 95% CI, 0.34 to 0.95) compared with persons with initial concentrations in the lowest quartile (<0.21 micromol/L [11.2 microg/dL]). Patients randomly assigned to beta carotene supplementation showed no reduction in relative mortality rates from all causes (adjusted RR, 1.03; 95% CI, 0.82 to 1.30) or from cardiovascular disease (adjusted RR, 1.16; 95% CI, 0.82 to 1.64). There was no evidence of lower mortality following supplementation among patients with initial beta carotene concentrations below the median for the study group., Conclusions: These analyses provide no support for a strong effect of supplemental beta carotene in reducing mortality from cardiovascular disease or other causes. Although the possibility exists that beta carotene supplementation produces benefits that are too small or too delayed to have been detected in this study, noncausal explanations should be sought for the association between plasma concentrations of beta carotene and diminished risk of death.

Objective: To evaluate the utility of the Centers for Disease Control and Prevention (CDC) Risk Questionnaire and a behavioral risk factor questionnaire in identifying children with blood lead concentrations of 0.48 mumol/L (10 micrograms/dL) or more., Design: Cross-sectional study of 463 urban Massachusetts children (6 to 72 months of age) screened for lead with venous blood., Results: Twenty-two percent of the children had elevated blood lead concentrations. Of the five CDC questions, only one was significantly associated with an increased adjusted odds ratio for elevated blood lead: having a sibling, housemate, or playmate who was followed up or treated for lead poisoning (odds ratio, 2.7; 95% confidence interval, 1.7 to 4.2; P < .001). Children who had at least one positive or equivocal response to any of the five CDC questions (n = 318 [68.7%]) were not at higher risk than were children who displayed a negative response to all five questions (odds ratio, 1.1; 95% confidence interval, 0.7 to 1.8; P = .69). Of nine behaviors surveyed, two were associated with an increased adjusted odds for elevated blood lead: use of a pacifier (odds ratio, 2.4; 95% confidence interval, 1.3 to 4.4; P = .01) and playing near the outside of the home (odds ratio, 3.4; 95% confidence interval, 2.0 to 5.8; P < .001)., Conclusions: In this population of children, the CDC risk questionnaire did not identify a group at higher risk for lead exposure. We suggest that practitioners in urban communities screen all children according to the same schedule. We conclude that risk factors differ by community and no risk questionnaire developed at the national level should be applied across communities to target screening.

Objective: To review the late sequelae of jejunoileal bypass (JIB) and the potential role of late surgical reversal in ameliorating morbidity and mortality following JIB., Design: Patients who underwent JIB between 1965 and 1977 were contacted and pertinent health-event information was gathered. Early sequelae were defined as disorders occurring within the first 2 years after JIB; late sequelae were those occurring after 2 years. Health events occurring between 0 and 23 years after JIB were documented., Setting: A private, tertiary referral center., Patients: Patients underwent JIB for morbid obesity that had failed medical and/or psychiatric interventions., Main Outcome Measures: Body mass index (BMI) (weight kilograms divided by the square of the height in meters), diarrhea, electrolyte imbalance, acute, and chronic liver disease, renal disease, JIB reversal, reason for JIB reversal, death, and cause of death., Results: A total of 453 morbidity obese patients underwent JIB. By 2 years following JIB, the mean (+/- SD) BMI dropped from 49.3 +/- 8.1 to 31.1 +/- 0.8 and remained at this level until year 15, after which weight gradually increased (BMI, 35.4 +/- 3.1). The most severe early complication was acute liver failure, which occurred in 7% of patients and caused seven deaths. At 15 years, the actuarial probability of the most common serious late complications related to JIB were renal disease (37%), with two deaths; diarrhea (29%); and liver disease (10%), with three deaths. One hundred thirty-eight patients (31%) had a bypass reversal. The most common indications for reversal were diarrhea and electrolyte disturbance (29%), renal disease (19%), and liver disease (17%). Fifty-six patients died more than 30 days after JIB: 64% before JIB reversal, 13% at the time of reversal, and 23% subsequently., Conclusions: Jejunoileal bypass is associated with progressive accrual of serious, sometimes life-threatening complications. Lifelong follow-up for early diagnosis and surgical reversal before life is threatened should reduce the morbidity and mortality associated with this procedure.

Background: Geographic variations in the use of hospital services are associated with differences in the availability of hospital beds. There continues to be uncertainty about the extent to which unmeasured case-mix differences explain these findings. Previous research showed that the number of occupied beds per capita in Boston was substantially higher than the number of occupied beds per capita in New Haven, Connecticut, and that overall rates of hospital utilization were higher for Boston residents than for New Haven residents., Methods: We used Medicare claims data to study cohorts of Medicare beneficiaries 65 years of age or older and residing in Boston or New Haven who were initially hospitalized for one of five indications (acute myocardial infarction, stroke, gastrointestinal bleeding, hip fracture, or potentially curative surgery for breast, colon, or lung cancer). Residents of Boston or New Haven who were discharged between October 1, 1987, and September 30, 1989, were enrolled in the cohort corresponding to the earliest such admission and followed for up to 35 months., Results: The relative rate of readmission in Boston as compared with New Haven was 1.64 (95 percent confidence interval, 1.53 to 1.76) for all cohorts combined, with a similarly elevated rate for each of the five clinical cohorts and each age, sex, and race subgroup examined. Hospital-specific readmission rates varied substantially among the hospitals in Boston and were higher than those in New Haven. No relation was found between mortality (during the first 30 days after discharge or over the entire study period) and either community or hospital-specific readmission rates., Conclusions: Regardless of the initial cause of the admission, Medicare beneficiaries who were initially hospitalized in Boston had consistently higher rates of readmission than did Medicare beneficiaries hospitalized in New Haven. Differences in the severity of illness are unlikely to explain these findings. One possible explanation is a threshold effect of hospital-bed availability on decisions to admit patients.

Background: The antioxidants beta carotene and vitamin E may play a role in cancer prevention. However, some studies have suggested that oral supplements of beta carotene may cause a decrease in serum levels of alpha tocopherol (vitamin E)., Purpose: We conducted this study to determine if beta carotene supplements affect serum levels of vitamin E and vice versa., Methods: Five hundred five patients in a clinical trial of antioxidant vitamins, used to prevent recurrences of colonic polyps, received either a placebo, 25 mg of beta carotene per day, 1 g ascorbic acid plus 400 mg alpha tocopherol per day, or all three agents combined. Serum levels of beta carotene and vitamin E were measured before and after 9 months of supplementation, using high-performance liquid chromatography., Results: Vitamin E levels changed very little among the groups receiving placebo or beta carotene and went up substantially and equally in the groups receiving vitamin E plus ascorbic acid or all three agents together. Conversely, beta carotene levels changed very little for the groups receiving placebo or ascorbic acid plus vitamin E but went up substantially and equally for the groups receiving beta carotene alone or all three agents., Conclusions: We conclude that oral supplementation with beta carotene for 9 months does not alter serum concentration of vitamin E and that supplementation with vitamin E plus ascorbic acid does not alter serum beta carotene levels.

Objective: To determine normal values for the urinary calcium/creatinine ratio (UCa/Cr) in infants. To assess the impact of short-term supplementation of infant formula with calcium and phosphorus on UCa/Cr in a group of infants., Design: We determined UCa/Cr in randomly collected urine samples from a group of children and adults. Short-term supplementation of infant formula with calcium glycerophosphate was carried out in 21 infants, and UCa/Cr was monitored in a before-and-after trial., Setting: A pediatric clinic at an academic center (infants and adults), and a day-care center (older children)., Participants: A total of 103 infants between 5 days and 7 months of age, 40 infants between 8 and 17 months of age, 41 children between 18 months and 6 years, and 31 adults., Results: The 95th percentiles for molar UCa/Cr for the different age groups were as follows: less than 7 months, 2.42 (0.86 mg/mg); 7 to 18 months, 1.69 (0.60 mg/mg); 19 months to 6 years, 1.18 (0.42 mg/mg); and adults, 0.61 (0.22 mg/mg). Regression analysis indicated a statistically significant decline in average UCa/Cr with age (R2 = 0.115, p < 0.0001 for log (UCa/Cr) vs log (age)). The geometric means for the two groups of infants were significantly greater than those of the older children and the adults (p < 0.05). Values for UCa/Cr in adults in our sample were comparable to those previously reported. We detected no significant changes in mean UCa/Cr during week-long periods of calcium supplementation of up to 1.8 gm of calcium and 1.39 gm of phosphorus per liter of formula., Conclusion: We conclude that normal values for UCa/Cr are much higher in infants than in older children and adults; UCa/Cr is age-related and declines gradually in the first several years of life, and short-term supplementation of infant formula with calcium glycerophosphate has minimal effect on UCa/Cr.

The authors have devised a meta-analytic method to summarize diagnostic test performances, which they describe along with a clinical example wherein they analyze the performances of real-time ultrasonography in eight studies of the detection of proximal deep venous thrombosis of the lower extremity, selected on the basis of specific inclusion criteria. To evaluate the evidence for fitting a summary receiver operating characteristic (ROC) curve, a test of correlation between the estimates of true-positive rate (TPR) and false-positive rate (FPR) is performed. A high positive correlation argues for summarizing the studies with an ROC curve. In the absence of such correlation, a test of homogeneity is applied separately to the estimates of sensitivity (TPR) and specificity (TNR) to evaluate whether differences among studies are due to chance alone. If the estimates are homogeneous, a summary point estimate and confidence intervals (CIs) are calculated. As a final step, subgroup analyses can be performed to assess alternative explanations of variability in TPR and FPR. Within groups defined by the presence or absence of symptoms of venous thrombosis, a negative correlation between TPR and FPR and homogeneity among studies were found. For symptomatic patients, the summary TPR was 0.97 with a 95% CI of (0.94, 0.99) and the summary TNR was 0.97 (0.95, 0.99). For asymptomatic patients, the summary TPR was 0.66 (0.50, 0.81), and the summary TNR was 0.96 (0.90, 0.99). The difference in TPR between symptomatic and asymptomatic patients was statistically significant. There was no evidence that test referral bias or lack of independent interpretation of test results influenced these findings.(ABSTRACT TRUNCATED AT 250 WORDS)