Disordered eating is not associated with musculoskeletal injury in university athletes.

TAKE HOME MESSAGE: Musculoskeletal injuries and disordered eating are prevalent in varsity-level athletes but are not associated in our participants.

How to predict and treat increased fracture risk in chronic kidney disease.

Men and women with chronic kidney disease (CKD) are at an increased risk of fracture, and this risk increases as kidney function deteriorates. Fractures are associated with morbidity, mortality and economic costs. Despite this, there is a paucity of data regarding how to evaluate risk for fractures in CKD and how to treat high-risk patients. Evidence suggests that bone mineral density (BMD) as assessed by dual-energy X-ray absorptiometry (DXA) is associated with fractures and can also predict future fractures in predialysis (stages 1-3) patients with CKD. In the absence of considerable abnormalities in markers of mineral metabolism, treatment with antiresorptive agents in men and women with early CKD at high fracture risk may be appropriate. Of note, recent data suggest that low BMD as measured by DXA can also predict fractures in patients with more advanced CKD (stages 4, 5 and 5D). However, treatment in patients with advanced CKD requires bone biopsy, the gold standard to assess bone turnover, prior to treatment. Further research, focusing on noninvasive methods to assess fracture risk and bone turnover, together with randomized controlled trials of treatments to reduce fractures in patients at all stages of CKD, is required.

Low bone mineral density and fractures in stages 3-5 CKD: an updated systematic review and meta-analysis.

SUMMARY: The utility of bone mineral density (BMD) testing in chronic kidney disease (CKD) is not known. We performed a meta-analysis of studies reporting on BMD and fracture in CKD. All but one study was cross-sectional. BMD was lower in those with CKD and fractures compared to those without fractures. INTRODUCTION: CKD is associated with an increased risk of fracture. The utility of dual energy X-ray absorptiometry (DXA) to assess fracture risk in CKD is unknown. METHODS: We performed an updated meta-analysis and systematic review of published studies that reported on the association between DXA and fracture (morphometric spine or clinical nonspine) in predialysis and dialysis CKD. We identified 2,894 potential publications, retrieved 292 for detailed review, and included 13. All but one study was cross-sectional and three reported on the ability of DXA to discriminate fracture status in predialysis CKD. Results were pooled using a random effects model and statistical heterogeneity was assessed using the I2 statistic. RESULTS: BMD was statistically significantly lower at the femoral neck, lumbar spine, the 1/3 and ultradistal radius in subjects with fractures compared to those without regardless of dialysis status. For example, femoral neck BMD was 0.06 g/cm2 lower in dialysis subjects and 0.102 g/cm2 lower in predialysis subjects with fractures compared to those without. Lumbar spine BMD was 0.05 g/cm2 lower in dialysis subjects and 0.108 g/cm2 lower in predialysis subjects with fractures compared to those without. Our meta-analysis was limited to studies with small numbers of subjects and even smaller numbers of fractures. All of the studies were observational and only one was prospective. There was statistical heterogeneity at the lumbar spine, 1/3 and ultradistal radius. CONCLUSIONS: Our findings suggest that BMD can discriminate fracture status in predialysis and dialysis CKD. Larger, prospective studies are needed.

The clinical utility of FRAX to discriminate fracture status in men and women with chronic kidney disease.

UNLABELLED: We assessed the ability of the World Health Organization's fracture risk assessment tool (FRAX), bone mineral density (BMD), and age to discriminate fracture status in adults with pre-dialysis chronic kidney disease (CKD). In adults with CKD, FRAX was able to discriminate fracture status but performed no better than BMD alone. INTRODUCTION: Patients with CKD are at increased risk for fracture but the best method to assess fracture risk is not known. METHODS: We assessed the ability of the World Health Organization's FRAX, compared with BMD at the femoral neck (FN), and age to discriminate fracture status (prevalent clinical nonspine and/or morphometric vertebral) in men and women, 18 years and older with pre-dialysis CKD. Results are presented as area under receiver operator characteristic curves (AUC) with 95% confidence intervals (CI). RESULTS: We enrolled 353 subjects; mean age was 65 ± 14 years; weight was 79 ± 18 kg, and estimated glomerular filtration rate was 28 ml/min/1.73 m(2). About one third of the subjects had a prevalent clinical nonspine and/or morphometric vertebral fracture. FRAX was able to discriminate among those with prevalent clinical nonspine fractures (AUC, 0.72; 95% CI, 0.65-0.78), morphometric vertebral fractures (AUC, 0.66; 95% CI, 0.59-0.73), and any fracture (AUC, 0.71; 95% CI, 0.65-0.77). The discriminative ability of BMD at the FN alone was similar to FRAX for morphometric vertebral and any fractures; FRAX performed better than BMD for prevalent clinical nonspine fractures (AUC for BMD alone, 0.66; 95% CI, 0.60-0.73). Compared to FRAX, the AUC for age alone was lower for all fracture types. CONCLUSIONS: Among men and women with CKD, FRAX is able to discriminate fracture status but performs no better than BMD alone.

Bone mineral density by DXA and HR pQCT can discriminate fracture status in men and women with stages 3 to 5 chronic kidney disease.

UNLABELLED: Fractures are common in chronic kidney disease (CKD). We determined if bone mineral density testing by dual energy X-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR pQCT) could discriminate fracture status in CKD patients. Both tests were able to discriminate fracture status. Further, the addition of HR pQCT measurements to DXA measurements did not improve fracture discrimination. INTRODUCTION: The optimal method to identify individuals with CKD at high fracture risk is unknown. METHODS: We determined if bone mineral density (BMD) by DXA and HR pQCT could discriminate fracture status in 211 adult men and women with stages 3 to 5 CKD, attending predialysis clinics in Toronto Canada, using logistic regression. Results are expressed as the odds ratio (OR) of fracture (prevalent vertebral and/or low trauma since age 40 years) per standard deviation decrease in the predictor adjusted for age, weight, sex, and CKD stage. We constructed receiver operating characteristic curves to examine the discriminative ability of BMD measures for fracture. RESULTS: Most participants were Caucasian men with a mean age of 63.3 ± 15.5 years. There were 77 fractures in 74 participants. Decreases in BMD were associated with increased fracture risk: OR = 1.56 (95% confidence interval (CI), 1.41 to 1.71) for BMD by DXA at the ultradistal radius, and OR = 1.24 (95% CI, 1.12 to 1.36) for cortical area by HR pQCT. Further, while both tests were able to discriminate fracture status, the addition of HR pQCT measures to BMD by DXA did not improve fracture discrimination ability. CONCLUSIONS: Among CKD patients not yet requiring renal replacement therapy, BMD by DXA is able to discriminate fracture status.

Methotrexate polyglutamates as a marker of patient compliance and clinical response in psoriasis: a single-centre prospective study.

BACKGROUND: Methotrexate is activated by the sequential addition of glutamic acid residues to form methotrexate polyglutamates (MTXPG(1-5)). MTXPG(1-5) inhibit enzymes of the folate-purine-pyrimidine pathways, and longer-chain MTXPG(3-5) species are more active. OBJECTIVES: To determine the pattern of erythrocyte MTXPG(1-5) in patients initiated on oral methotrexate for psoriasis, and to investigate the potential utility of MTXPGs as markers of compliance and/or clinical response. METHODS: This was a single-centre, prospective study of 55 adult patients with chronic plaque psoriasis initiated on weekly oral methotrexate. Erythrocyte MTXPG(1-5) concentrations were measured (at weeks 4, 8, 12, 24 and 52) using high-performance liquid chromatography. Methotrexate responders achieved ≥ 50% improvement in Psoriasis Area and Severity Index or physician's global score of 'clear'/'nearly clear' at 24 weeks. RESULTS: MTXPG levels were measured in 14-33 patients at each time point. All MTXPG(1-5) species were detected at week 4 of therapy. Steady state for long-chain MTXPG(3-5) and total MTXPG(1-5) was achieved by week 24. MTXPG(3) emerged as the predominant MTXPG species (from week 12 onwards) and reflected overall polyglutamate status (correlating strongly with MTXPG(2-5) , MTXPG(3-5) and MTXPG(4-5) ; R = 0·76-0·95, P < 1·55 × 10(-5)). Age, renal function and sex were not significant determinants of MTXPG(3) concentration. No significant association was identified between MTXPG and adverse events or responder status. CONCLUSIONS: This is the first study to demonstrate the prospective accumulation of MTXPG(1-5) in patients with psoriasis. The detection of MTXPGs early in therapy and the establishment of a steady state with continuous treatment may offer measuring of MTXPG as a test to monitor patient compliance with therapy. Larger studies are required to determine the role of MTXPG as a potential biomarker of clinical response.

Fracture risk assessment in patients with chronic kidney disease.

Fractures are common in patients with chronic kidney disease (CKD) and associated with substantially high morbidity and mortality. Bone mass measurements are commonly used to assess fracture risk in the general population, but the utility of these measurements in patients with CKD, and specifically among those on hemodialysis, is unclear. This review will outline the epidemiology and etiology of fractures in patients with CKD with a particular emphasis on men and women on hemodialysis. As well, we will summarize the published data, which describes the association between risk factors for fracture (including bone mass measurements, biochemical markers of mineral metabolism, and muscle strength) and fractures in patients with CKD. Patients with CKD suffer from fractures due to impairments in bone quantity, bone quality, and abnormalities of neuromuscular function. There is a paucity of evidence on the associations between bone quality, bone turnover markers, neuromuscular function, and fractures in patients with CKD. Furthermore, the complex etiology of fractures combined with the technical limitations of bone mineral density testing, both by dual energy X-ray absorptiometry (DXA) and by peripheral quantitative tomography (pQCT), limits the clinical utility of bone mass measurements for fracture prediction in CKD; this is particularly true among patients with stages 4 and 5 CKD. Further prospective studies to identify noninvasive measures of bone strength that can be used for fracture risk assessment are needed.

High prevalence of subtle and severe menstrual disturbances in exercising women: confirmation using daily hormone measures.

BACKGROUND: The identification of subtle menstrual cycle disturbances requires daily hormone assessments. In contrast, the identification of severe menstrual disturbances, such as amenorrhea and oligomenorrhea, can be established by clinical observation. The primary purpose of this study was to determine the frequency of subtle menstrual disturbances, defined as luteal phase defects (LPD) or anovulation, in exercising women, with menstrual cycles of 26-35 days, who engage in a variety of sports, both recreational and competitive. Secondly, the prevalence of oligomenorrhea and amenorrhea was also determined via measurement of daily urinary ovarian steroids rather than self report alone. METHODS: Menstrual status was documented by daily measurements of estrone and pregnanediol glucuronide and luteinizing hormone across two to three consecutive cycles and subsequently categorized as ovulatory (Ovul), LPD, anovulatory (Anov), oligomenorrheic (Oligo) and amenorrheic (Amen) in sedentary (Sed) and exercising (Ex) women. RESULTS: Sed (n = 20) and Ex women (n = 67) were of similar (P > 0.05) age (26.3 +/- 0.8 years), weight (59.3 +/- 1.8 kg), body mass index (22.0 +/- 0.6 kg/m2), age of menarche (12.8 +/- 0.3 years) and gynecological maturity (13.4 +/- 0.9 years). The Sed group exercised less (P < 0.001) (96.7 +/- 39.1 versus 457.1 +/- 30.5 min/week) and had a lower peak oxygen uptake (34.4 +/- 1.4 versus 44.3 +/- 0.6 ml/kg/min) than the Ex group. Among the menstrual cycles studied in the Sed group, the prevalence of subtle menstrual disturbances was only 4.2% (2/48); 95.8% (46/48) of the observed menstrual cycles were ovulatory. This finding stands in stark contrast to that observed in the Ex group where only 50% (60/120) of the observed menstrual cycles were ovulatory and as many as 50% (60/120) were abnormal. Of the abnormal cycles in the Ex group, 29.2% (35/120) were classified as LPD (short, inadequate or both) and 20.8% (25/120) were classified as Anov. Among the cycles of Ex women with severe menstrual disturbances, 3.5% (3/86) of the cycles were Oligo and 33.7% (29/86) were Amen. No cycles of Sed women (0/20) displayed either Oligo or Amen. CONCLUSIONS: This study suggests that approximately half of exercising women experience subtle menstrual disturbances, i.e. LPD and anovulation, and that one third of exercising women may be amenorrheic. Estimates of the prevalence of subtle menstrual disturbances in exercising women determined by the presence or absence of short or long cycles does not identify these disturbances. In light of known clinical consequences of menstrual disturbances, these findings underscore the lack of reliability of normal menstrual intervals and self report to infer menstrual status.

Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial.

CONTEXT: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressant, yet it is not known whether one SSRI is more effective than another. OBJECTIVE: To compare the effectiveness of 3 SSRIs (paroxetine, fluoxetine, and sertraline) in depressed primary care patients. DESIGN: Open-label, randomized, intention-to-treat trial, with patient enrollment occurring in April-November 1999. SETTING: Thirty-seven clinics in 2 US primary care research networks. PATIENTS: A total of 573 depressed adult patients for whom their primary care physician thought that antidepressant therapy was warranted and who completed a baseline interview. INTERVENTIONS: Patients were randomly assigned to receive paroxetine (n = 189), fluoxetine (n = 193), or sertraline (n = 191) for 9 months. Primary care physicians were allowed to switch patients to a different SSRI or non-SSRI antidepressant if they did not adequately respond to or tolerate the initial SSRI. MAIN OUTCOME MEASURES: The primary outcome measure was change in the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) Mental Component Summary score (range, 0-100), compared across treatment groups at 1, 3, 6, and 9 months. Secondary outcomes included other depression and psychological measures, multiple measures of social and work functioning, and other domains of health-related quality of life, such as physical functioning, concentration and memory, vitality, bodily pain, sleep, and sexual functioning. RESULTS: Follow-up interviews were successfully completed in 94% of patients at 1 month, 87% at 3 months, 84% at 6 months, and 79% at 9 months. Responses to the 3 SSRIs were comparable on all measures and at all time points. The mean change in the SF-36 Mental Component Summary score at 9 months was + 15.8 in the paroxetine group, + 15.1 in the fluoxetine group, and + 17.4 in the sertraline group. The drugs were also associated with similar incidences of adverse effects and discontinuation rates. CONCLUSIONS: The SSRI antidepressants paroxetine, fluoxetine, and sertraline were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of this trial.

Tocolytic therapy for preterm labour: assessing its potential for reducing preterm delivery.

Preterm labour (PTL) is a major contributor to preterm delivery (PTD) but delivery is often not preventable by current therapies. We conducted this study to determine the proportion of women with PTL who were and who were not candidates for tocolytic therapy. The cohort comprised residents of Olmsted County, Minnesota who delivered at >20 weeks' gestation in 1985--94 and who experienced PTL. Medical records were abstracted to identify episodes of PTL, its treatment and outcome. We developed an algorithm that accounted for gestation at delivery and pregnancy complications to determine the proportion of pregnancies complicated by PTL that were candidates for tocolytic therapy. Of 651 pregnancies complicated by PTL, a 50% probability sample, stratified by delivery year, were selected and abstracted. The cumulative incidence of PTL ranged from 3.6 to 6.4 per 100 deliveries of live or stillborn infants. Tocolysis was not contraindicated for 49.4% of all women with PTL and for a third of women with only one PTL episode. Delivery was delayed to >35 weeks in 53.8% of candidates for tocolysis. Only an additional 11.7% of women with one or more PTL episodes could have had their PTD delayed beyond 35 weeks if a perfect tocolytic therapy had been available. Many pregnancies complicated by PTL occurred at > or =35 weeks or involved maternal or obstetric factors that contraindicated tocolytic medications. The maximum incremental benefit that could be expected of a new safe and efficacious tocolytic therapy would be to reduce current PTD rates resulting from PTL by about 12%.

Hispanic and Anglo college women's risk factors for substance use and eating disorders.

This study investigated the role of temperament style (Novelty Seeking and Harm Avoidance) of Hispanic American and Anglo college women in moderating and mediating the relationship between family addiction/family functioning and offspring problem behaviors. The sample was comprised of 67 Hispanic American and 770 Anglo undergraduate women. Findings of this study indicate that the processes of risk that lead to substance use and eating disorders follow different routes for Hispanic American and Anglo women. Novelty Seeking and Harm Avoidance were found to be important factors in both moderating and mediating the effects of parental drinking and family dysfunction for both Hispanic and Anglo college women.

The virtual standardized patient. Simulated patient-practitioner dialog for patient interview training.

We describe the Virtual Standardized Patient (VSP) application, having a computerized virtual person who interacts with medical practitioners in much the same way as actors hired to teach and evaluate patient assessment, diagnosis, and interviewing skills. The VSP integrates technologies from two successful research projects conducted at Research Triangle Institute. AVATALK provides natural language processing, emotion and behavior modeling, and composite facial expression and lip-shape modeling for a natural patient-practitioner dialog. Trauma Patient Simulator provides case-based patient history and trauma casualty data, real-time physiological modeling, interactive patient assessment, 3-D scenario simulation, and instructional record-keeping capabilities. The VSP offers training benefits that include enhanced adaptability, availability, and assessment.

Assessing the Saskatchewan database for outcomes research studies of depression and its treatment.

This study was conducted to evaluate the validity of using the Saskatchewan Health administrative claims databases for conducting depression research. To develop a claims-based definition of depression, we identified a cohort of individuals who began a "new" period of antidepressant use (no use 180 days prior) from which we selected a stratified random sample (n = 600) for medical record abstraction. The medical record diagnosis was used as the gold standard for judging our database definitions of depression. After defining a primary database definition of depression, we tried to refine it using medically probable scenarios and assessed refinement by agreement statistics. Defining depression with ICD9 codes 296 (affective disorders), 309 (adjustment reaction), and 311 (depressive disorders), the sensitivity (Se), specificity (Sp), positive (PV+) and negative predictive (PV-) values were: 71%, 85%, 86%, and 70%, respectively. Algorithms that limited the number of false-negatives resulted in: Se = 84% and PV- = 77% whereas those that limited false-positives resulted in: Sp = 90% and PV+ = 86%. Although our depression definition requires treatment with antidepressants, this definition will allow us to conduct future studies of depression and its treatment using the Saskatchewan Health databases.

A meta-analysis comparing the effectiveness of buprenorphine and methadone.

Increases in the use of illicit opiates have refocused attention on these drugs. One outgrowth of this attention has been the increased consideration of pharmacotherapies to provide alternatives to methadone maintenance. Buprenorphine is one new tool used in the attenuation of illicit opiate use. Like methadone, buprenorphine produces cross-tolerance to other opiates. However, it may have advantages over methadone including a longer duration, limited withdrawal syndrome, and increased safety. Buprenorphine's ability to serve as a replacement drug for illicit opiate use is well documented, and efforts have recently been made to compare the drug with methadone. The purpose of this study was to provide a meta-analysis of all available research reporting a controlled comparison of buprenorphine and methadone. This analysis provided a rating of the comparative efficacy of each drug, thus giving clinicians an additional guide when selecting an appropriate course of treatment. Findings suggest a relative equality in the efficacy of buprenorphine and methadone, although patients receiving methadone were less likely to test positive for illicit opiate use. Past experience with methadone maintenance acted as a moderating variable, however, such that those receiving buprenorphine were more likely to stay drug-free in studies that included patients with prior methadone experience.

Healthcare use among U.S. women aged 45 and older: total costs and costs for selected postmenopausal health risks.

The purpose of this study is to estimate the level of healthcare use and costs incurred by postmenopausal women overall and for these selected conditions: cardiovascular disease, osteoporosis, breast cancer, and gynecological cancers. National healthcare survey and discharge data were used to estimate healthcare use by women aged 45 and older. Clinical Classification for Health Policy Research (CCHPR) codes were used to identify patients whose primary diagnosis or procedure corresponded with the selected conditions. National weights were used to estimate resource use. Treatment costs were estimated using cost/charge ratios or the Medicare fee schedule to calculate costs for each individual procedure. Estimated total annual medical care treatment costs for women 45 and older were about $186 billion in 1997 dollars, including about $60.4 billion for cardiovascular disease, $12.9 billion for osteoporosis, and $5.0 billion for breast and gynecological cancers. For each condition, estimated resource use and costs are reported for hospitalization, outpatient, nursing home, and home healthcare services. Resource use and costs are also reported by age and expected source of payment. The economic burden of disease for conditions commonly affecting postmenopausal women is substantial. Prior research establishes that hormone replacement therapy (HRT) may be effective in reducing the burden of disease among women who continue preventive therapy for many years, but few at-risk women do so. New alternatives for prevention, such as selective estrogen receptor modulators (SERMs), may be effective in reducing the burden of disease among postmenopausal women.

Pharmacological treatment of alcohol dependence: a review of the evidence.

CONTEXT: Alcoholism affects approximately 10% of Americans at some time in their lives. Treatment consists of psychosocial interventions, pharmacological interventions, or both, but which drugs are most effective at enhancing abstinence and preventing relapse has not been systematically reviewed. OBJECTIVE: To evaluate the efficacy of 5 categories of drugs used to treat alcohol dependence--disulfiram, the opioid antagonists naltrexone and nalmefene, acamprosate, various serotonergic agents (including selective serotonergic reuptake inhibitors), and lithium. DATA SOURCES: Reports of randomized controlled trials, nonrandomized trials, and other study designs in English, French, and German identified from multiple searches of MEDLINE, EMBASE, and specialized databases; hand searching bibliographies of review articles; searches for unpublished literature; and discussions with investigators in the field. STUDY SELECTION: We included all studies on alcohol-dependent human subjects aged 18 years or older from all inpatient and outpatient settings between 1966 and December 1997 that met our inclusion criteria. DATA EXTRACTION: We abstracted the following information: study design and blinding, diagnostic instrument and severity assessment, drug interventions and cointerventions, demographic and comorbidity details about patients, compliance, and numerous outcome measures (eg, relapse, return to drinking, drinking or nondrinking days, time to first drink, alcohol consumed per unit of time, craving). We graded quality of the individual articles (scale, 0-100) independently from the strength of evidence for each drug class (A, strong and consistent evidence of efficacy in studies of large size and/or high quality; B, mixed evidence of efficacy; C, evidence of lack of efficacy; and I, insufficient evidence). DATA SYNTHESIS: Of 375 articles evaluated, we abstracted and analyzed data from 41 studies and 11 follow-up or subgroup studies. Naltrexone (grade A) reduces the risk of relapse to heavy drinking and the frequency of drinking compared with placebo but does not substantially enhance abstinence, ie, avoidance of any alcohol consumption. Acamprosate (grade A, from large-scale studies in Europe) reduces drinking frequency, although its effects on enhancing abstinence or reducing time to first drink are less clear. Controlled studies of disulfiram (grade B) reveal a mixed outcome pattern--some evidence that drinking frequency is reduced but minimal evidence to support improved continuous abstinence rates. The limited data on serotonergic agents were not very promising (grade I), although most studies were confounded by high rates of comorbid mood disorders. Lithium lacks efficacy (grade C) in the treatment of primary alcohol dependence. CONCLUSIONS: Recent reports documenting that naltrexone and acamprosate are more effective than placebo in the treatment of alcoholism justify clinical interest in use of these medications for alcohol-dependent patients. Use of disulfiram is widespread but less clearly supported by the clinical trial evidence; however, targeted studies on supervised administration of disulfiram may be warranted. Use of existing serotonergic agents or lithium for patients with primary alcohol dependence does not appear to be supported by the efficacy data available at this time; these medications may still have a positive effect in patients with coexisting psychiatric disorders.

Demographics, health behaviors, and past drug use as predictors of recall accuracy for previous prescription medication use.

Drug data for pharmacoepidemiologic studies are often ascertained by self-report, but little research has addressed the factors influencing its accuracy. Stratified random sampling was used to select individuals for a study comparing interview data on past prescription drug use with dispensation information from the Group Health Cooperative of Puget Sound pharmacy database. The strata included age, gender, and recency of use. Recall accuracy and its determinants were evaluated for repetitively used non-steroidal anti-inflammatory drugs (NSAIDs), short-term NSAIDs (only a single dispensation), and post-menopausal estrogens. We investigated whether recall accuracy was influenced by education, marital status, race, smoking, alcohol consumption, cumulative drug history, the number of different NSAIDs or estrogens dispensed (both by name and dosage), and the number of dispensations of the drug in question. For repetitively used NSAIDs, recall accuracy was positively associated with the number of NSAID dispensations (the odds of recall were 1.7 [95% confidence interval {CL}: 1.3-2.2] times greater for each additional four dispensations of the NSAID), the total number of drugs dispensed and the number of different NSAIDs dispensed. For estrogen and short-term NSAID use, only higher educational attainment improved recall accuracy: the odds of recall were 4.1 (95% CI: 1.4-11.7) and 2.1 (95% CI: 1.0-4.7) times greater for those with some college compared with those with only a high school degree, respectively. This study demonstrates that predictors of recall accuracy for previous medication use differ by the type of drug and the repetitiveness of its use.

Biochemical epidemiology of gallbladder cancer.

To evaluate the a priori hypotheses that an increased level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four cases with newly diagnosed histologically confirmed gallbladder cancer were compared with 264 controls with cholelithiasis or choledocholithiasis in the absence of cancer and with 126 controls with normal biliary tracts. All study subjects were undergoing abdominal surgery. Interview data were collected for all study subjects, as well as blood, bile, and gallstone specimens when feasible. Sera were analyzed for carcinoembryonic antigen, cholesterol concentration, and total bile acids. Bile specimens were analyzed for carcinoembryonic antigen; and for concentration of bile salts; cholesterol; phospholipids; and the glycine and taurine conjugates of cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic, and lithocholates; sulfoglycolithocholate; and sulfotaurolithocholate. Gallstone specimens were analyzed for the percentage of cholesterol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus the two control groups (median 11.7 nmol/mL vs. 9.3 nmol/mL for stone controls and 8.2 nmol/L for nonstone controls, P < or = .02 for each pairwise comparison). Biliary bile acids were markedly decreased in the cases (median 3.98 micromol/mL vs. 33.09 micromol/mL, and 154.0 micromol/L, respectively, P < or = .0001 for each comparison), even after excluding those with a serum bilirubin higher than 2.0 mg/dL. Bile cholesterol was lower for the cases as well (median 1.70 micromol/mL vs. 4.90 micromol/mL, and 16.81 micromol/ mL, respectively, P < or = .02), as was the concentration of bile phospholipids (median 2.97 micromol/mL vs. 6.26 micromol/mL, and 52.69 micromol/mL, P = .1 and .0004, respectively). Contrary to our a priori hypothesis, there was no difference between the cases and either control group in their bile concentrations of lithocholate, the proportion of bile acids which were sulfated, or the concentration of nonsulfated lithocholate. However, the cases had a higher concentration of ursodeoxycholate (UDC) (P < .004 for both control groups), especially glycoursodeoxycholate (P < .001 for both control groups). A previously published suggestion that gallstone size differed between cases and controls was not confirmed. In conclusion, cases with gallbladder cancer differed from controls with stones and from controls with normal biliary tracts in their serum and bile biochemistries. These findings may be a reflection of the disease process, or may provide useful clues to its pathogenesis.