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J Concato

Publications and source records attributed to J Concato.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical epidemiological quality in molecular genetic research: the need for methodological standards.

CONTEXT: A genetic basis has been identified for many medical conditions and some molecular tests have been commercialized. However, little attention has been given to the quality of clinical epidemiology in molecular studies. OBJECTIVE: To examine the clinical epidemiological quality of recent publications on molecular genetic analysis. DESIGN: Cross-sectional study of original research articles published in 1995, identified by manually searching 4 general clinical journals. Of 83 articles identified, 40 were selected for analysis; these 40 discussed molecular genetic techniques, studied 10 or more patients, and had inferential conclusions. MAIN OUTCOME MEASURE: Compliance of the selected articles with 7 methodological standards for clinical epidemiological science (reproducibility, objectivity, delineation of case group, adequacy of spectrum in case group, delineation of comparison group, adequacy of comparison group, and quantitative summary of results). RESULTS: Among the 40 inferential articles that studied 10 or more patients, only 5 (12.5%) complied with all 7 applicable standards, and 10 (25.0%) complied with all but 1 standard, whereas 25 articles (62.5%) failed to comply with 2 or more standards and 9 (22.5%) failed 4 or 5 standards. Most articles did not comply with standards for reproducibility (n = 25, 62.5%) or objectivity (n = 27, 67.5%); however, the majority of articles did comply with standards for adequacy of case group (n = 35, 87.5 %), adequacy of comparison group (n = 35, 87.5%), and quantitative summary of results (n = 36, 90%). CONCLUSIONS: Despite major laboratory advances in molecular genetic analysis, our data suggest that reported applications in clinical journals often have troubling omissions, deficiencies, and lack of attention to the different, but necessary, principles of clinical epidemiological science. Without suitable attention to fundamental methodological standards, the expected benefits of molecular genetic testing may not be achieved.

Clinical Medicine↗
PubMed1999

Differences in cervical cancer mortality among black and white women.

OBJECTIVE: To determine whether stage of disease and treatment patterns account for mortality differences between black and white women with cervical cancer. METHODS: Using data obtained from the Surveillance, Epidemiology, and End Results (SEER) Program for 1988-1994, we determined the associations between race and stage, and race and treatment. Racial differences in survival for up to 7 years of follow-up were adjusted for age, marital status, SEER location, International Federation of Gynecology and Obstetrics (FIGO) stage of disease, lymph node status, grade, histology, and treatment. RESULTS: Cumulative mortality was 36% (366 deaths in 1029 women) for black women and 24% (1215 deaths in 5021 women) for white women; unadjusted hazard ratio was 1.60 (95% confidence interval [CI] 1.43, 1.80). Black women were more likely to present with advanced disease than white women (43.8% compared with 34.8%). In a model adjusting for demographics and FIGO stage, the hazard ratio for black women compared with white women decreased to 1.35 (95% CI 1.19, 1.54). Treatment varied by race, with black women receiving surgery less often (33.5% compared with 48.2%, respectively) and radiation therapy more often (35.3% and 25.2%, respectively) than white women. In a comprehensive model including demographic factors, FIGO stage, other tumor characteristics, and treatment, the adjusted hazard ratio for mortality remained high for black women at 1.30 (95% CI 1.14, 1.48). CONCLUSION: Race remains an independent predictor of cervical cancer survival after accounting for age, stage of disease, treatment patterns, and other factors. Future studies should assess racial differences in clinical severity of disease, comorbidity, and socioeconomic status.

Adult↗
PubMed1999

Alcohol use and functional disability among cognitively impaired adults.

BACKGROUND: The extent to which alcohol exposure increases risk for functional disability among older adults with cognitive impairment has not previously been assessed. OBJECTIVE: To examine the potential relationship between alcohol use and functional disability among older cognitively impaired adults. DESIGN: Retrospective medical record review. SETTING: Hospital-based geriatric assessment center. PARTICIPANTS: Two hundred forty-two consecutive participants with Mini-Mental Status Examination scores of < or = 24. MEASUREMENTS: Proxy-reported alcohol intake was classified in categories of never, former, light (< 1 drink/week), moderate (> or = 1 but < 14 drinks/week), and heavy (> or = 14 drinks/week) drinkers, and functional status was determined by proxy-reported performance in seven basic (BADL) and seven instrumental (IADL) activities of daily living (0 = poorest function and 14 = best function). RESULTS: Compared with never drinkers, moderate drinkers demonstrated higher mean BADL (12.2 vs 11.4, P = .033) and IADL scores (6.6 vs 5.6, P = .067), whereas heavy drinkers had higher BADL (12.8 vs 11.4, P = .019) but lower IADL scores (4.8 vs 5.6, P = .425). Former drinkers demonstrated both lower BADL (10.8 vs 11.4, P = .107) and IADL scores (3.9 vs 5.6, P = .011) compared with never drinkers. Evaluation of a potential dose-response effect was limited due to low numbers of light and heavy drinkers. CONCLUSIONS: Among cognitively impaired adults, moderate and heavy drinkers demonstrated better BADL function, whereas former drinkers had poorer IADL function, compared with never drinkers. Prospective studies that incorporate additional measures of exposure (e.g., cumulative lifetime consumption) and function (e.g., performance-based tests) may provide a more comprehensive understanding of alcohol's effects among older cognitively impaired adults.

Activities of Daily Living↗
PubMed1998

Importance of functional measures in predicting mortality among older hospitalized patients.

CONTEXT: Measures of physical and cognitive function are strong prognostic predictors of hospital outcomes for older persons, but current risk adjustment and burden of illness assessment indices do not include these measures. OBJECTIVE: To evaluate and validate the contribution of functional measures to the ability of 5 standard burden of illness indices (Charlson, Acute Physiology and Chronic Health Evaluation [APACHE] II, Disease Staging, All Patient Refined Diagnosis Related Groups, and a clinician's subjective rating) in predicting 90-day and 2-year mortality among older hospitalized patients. DESIGN: Two prospective cohort studies. SETTING: General medicine service, university teaching hospital. PATIENTS: For the development cohort, 207 consecutive patients aged 70 years or older, and for the validation cohort, 318 comparable patients. MAIN OUTCOME MEASURE: Death within 90 days and 2 years from the index admission. RESULTS: In the development cohort, 29 patients (14%) and 81 patients (39%) died within 90 days and 2 years, respectively. A functional axis was developed using 3 independent risk factors: impairment in instrumental activities of daily living, Mini-Mental State Examination score of less than 20, and shortened Geriatric Depression Scale score of 7 or higher, creating low-, intermediate-, and high-risk groups with associated mortality rates of 20%, 32%, and 60%, respectively (P<.001); the C statistic for the final model was 0.69. The corresponding mortality rates in the validation cohort, in which 59 (19%) and 138 (43%) died within 90 days and 2 years, respectively, were 24%, 45%, and 60% (P<.001); the C statistic for the final model was 0.66. For each burden of illness index, the functional axis contributed significantly to the predictive ability of the model for both 90 days and 2 years. When the functional axis and each burden of illness measure were analyzed in cross-stratified format, mortality rates increased progressively from low-risk to high-risk functional groups within strata of burden of illness indices (double-gradient phenomenon). The contributions of functional and burden of illness measures were substantive and interrelated. CONCLUSIONS: Functional measures are strong predictors of 90-day and 2-year mortality after hospitalization. Furthermore, these measures contribute substantially to the prognostic ability of 5 burden of illness indices. Optimal risk adjustment for older hospitalized patients should incorporate functional status variables.

Activities of Daily Living↗
PubMed1998

Prognostic staging system for recurrent, persistent, and second primary cancers of the oral cavity and oropharynx.

OBJECTIVE: To develop a practical staging system for predicting mortality of patients with recurrent squamous cell tumors of the oral cavity and oropharyngeal mucosa. DESIGN AND SETTING: An inception cohort at an academic medical center. PATIENTS: A total of 308 patients who had evidence of recurrent, persistent, or second primary tumors of the oral cavity and oropharynx between January 1, 1980, and December 31, 1991, of whom 162 (52.6%) met inclusion criteria. MAIN OUTCOME MEASURE: One-year mortality. RESULTS: The median survival time was 10 months. In bivariate analysis, the TNM stage of the recurrent tumor, invasion of pharyngeal constrictors and the floor-of-mouth muscles, weight loss, local and systemic symptoms, and eating function had significant effects on mortality. Multivariable analysis (done by conjunctive consolidation and Cox regression) identified constrictor invasion, the TNM stage of the recurrence, and weight loss as having a substantial effect on mortality. A composite 4-stage system using these 3 variables demarcated 1-year survival rates of 88.2% (30/34), 71.9% (23/32), 32.6% (16/49), and 4.2% (2/47). CONCLUSIONS: The TNM status of recurrent tumors predicts mortality, but constrictor muscle invasion and weight loss also have major prognostic importance. The consolidation of these variables into a composite staging system successfully stratifies patients with widely divergent mortality rates. Improved staging of recurrent head and neck tumors can lead to more effective decisions about the comparisons and merits of additional treatment.

Aged↗
PubMed1998

The quest for "power": contradictory hypotheses and inflated sample sizes.

To have the "power" of avoiding undersized clinical trials, the customary statistical strategy used in the past few decades is aimed at rejecting both a null stochastic hypothesis and a contradictory alternative hypothesis. This approach gives a trial the "power" to confirm the "insignificance" of differences much smaller than the large value of delta desired in trials done to show efficacy. In many instances, however, a prime problem is that the current "double-significance" approach produces sample sizes 2-3 times larger than needed for stochastic confirmation of large differences (> or =delta). The inflated sample sizes and consequent problems can be avoided if a realistic value for delta is chosen and maintained thereafter, and if an adequate "capacity" is calculated for "single significance."

Bias↗
PubMed1998

Physician awareness of alcohol use disorders among older patients.

OBJECTIVES: To determine primary care physicians' awareness of, and screening practices for, alcohol use disorders (AUDs) among older patients. DESIGN: Cross-sectional telephone survey of a national sample of primary care physicians. PARTICIPANTS: Physicians randomly sampled from the Masterfile database of the American Medical Association and stratified by specialty as family practice physicians, internal medicine physicians, and either family practice or internal medicine physicians with geriatric certification. MAIN RESULTS: A total of 171 physicians were contacted: 155 (91%) agreed to participate, and responses were analyzed from 150 (50 family practice, 50 internal medicine, 50 with geriatric certification). The median prevalence estimate of AUDs among older patients was 5% for each group of physicians. In contrast to published prevalence rates of AUDs ranging from 5% to 23%, 38% of physicians reported prevalence estimates of less than 5%, and 5% cited estimates of at least 25%. Compared with the other groups, the physicians with geriatric certification were more likely to report no regular screening (42% vs 20% for family practice vs 18% for internal medicine, p = .01), while younger (<40 years) and middle-aged physicians (40-55 years) reported higher annual screening rates relative to older physicians (>55 years) (77% vs 60% vs 44% respectively, p = .03). Among physicians who regularly screened (n = 110), 100% asked quantity-frequency questions, 39% also used the CAGE questions, and 15% also cited use of biochemical markers. CONCLUSIONS: Primary care physicians may "underdetect" AUDs among older patients. The development of age-specific screening methods and physician education may facilitate detection of older patients with (or at risk for) these disorders.

Aged↗
PubMed1997

Asking patients what they like: overlooked attributes of patient satisfaction with primary care.

PURPOSE: Ask patients to describe important attributes of their primary health care; and use the responses to develop a taxonomy for classifying patient satisfaction. DESIGN: Open-ended questions were administered to patients immediately after a clinic visit. SETTING: Primary care clinics at an academically affiliated Veterans Affairs Medical Center in New England. PATIENTS: Two hundred two of 204 randomly selected English-speaking patients who agreed (and were able) to participate. INTERVENTIONS: Clinimetric methods were used to obtain responses to three open-ended questions about what patients liked, disliked, and would like to see changed about their care. These "raw" descriptions were then combined into pertinent groups and arranged as a taxonomy of patient satisfaction. RESULTS: The taxonomy was divided into five main axes referring to physician staff, nonphysician staff, attributes of the clinic, related services, and the institution. The axes contained a total of 34 items related to patient satisfaction. The items have demonstrable face validity, and are likely to be "transparently" sensible to clinicians and policy makers, but many of the items-such as problems with parking-were not included in either of two existing psychometric instruments used to measure patient satisfaction in the same clinics. CONCLUSIONS: The clinimetric strategy leads to a simple, clinically relevant, and easily understood assessment of patient satisfaction with health care services. The assessment can be done with three simple questions; and the responses can be catalogued, when desired, in a suitable taxonomy.

Adult↗
PubMed1997

What is a screening test? Misclassification bias in observational studies of screening for cancer.

OBJECTIVE: To demonstrate the importance of accurately identifying clinical distinctions of subjects in observational studies of screening. DESIGN: Simulated case-control studies. SETTING: The West Haven Veterans Affairs Medical Center. PATIENTS: Fifty-two men diagnosed with prostate cancer in 1988 or 1989 had 252 digital rectal examinations (DREs) in the preceding 5 years. A classification scheme used patient symptoms and the results of prior DREs to assign the last DRE before the diagnosis of cancer to one of the following categories: definite screening, likely screening, probable screening, not screening, or other and unknown. Sixty-five percent of the DREs were classified as definite or likely screening, and another 15% were classified as probable screening. MAIN RESULTS: Changing the definition of a screening DRE from one including to one excluding probable DREs lowered the frequency of screening in case subjects more than it did in case controls, and thus lowered the odds ratio (OR), making screening appear to be more protective. Even when DRE was not protective, the ORs for the effectiveness of screening with the more restrictive definition ranged from 0.21 to 0.83 in 36 simulated case-control studies that differed according to the frequency of screening, the prevalence of cancer in case controls, and the extent of misclassification error. CONCLUSIONS: If clinical distinctions in the performance of screening tests are not classified appropriately, observational studies will misrepresent the proportion of subjects exposed to screening interventions and produce biased results.

Aged↗
PubMed1997

Monte Carlo methods in clinical research: applications in multivariable analysis.

BACKGROUND: Monte Carlo methods use "simulated" analyses with random numbers for solving problems, particularly those that defy solutions using mathematical theory alone. Research using Monte Carlo simulations is very popular in many branches of science and is sometimes done in clinical investigation. The origins and basic strategy of the technique, however, may not be well known to clinical researchers. The purpose of this paper is to describe the history and general principles of Monte Carlo methods and to demonstrate how Monte Carlo simulations were recently applied to examine a phenomenon in multivariable statistical analysis called the number of outcome events per independent variable (EPV). For example, in a cohort of 200 people, with 50 deaths and 5 independent (predictor) variables, EPV = 50/5 = 10. METHODS: The "real-world" data came from a clinical trial of 673 patients in which 7 variables were cogent predictors of 252 deaths, so that EPV = 252/7 = 36. For the Monte Carlo simulations, special models were used while allowing simulations of proportional hazards and logistic regression to maintain the basic relationship of variables and the same size of the original population, at EPV values of 2, 5, 10, 15, 20, and 25. RESULTS: The Monte Carlo simulations confirmed a previously undocumented "rule of thumb" stating that when the EPV is less than 10-20, the algebraic models used in logistic regression and proportional hazards regression may be unreliable, leading to imprecise or spurious results. CONCLUSION: Monte Carlo techniques offer attractive methods for clinical investigators to use in solving problems that are not amenable to customary mathematical approaches.

Humans↗
PubMed1997

Screening for skin cancer in primary care settings.

OBJECTIVE: To estimate the frequency of recorded screening for skin cancer in primary care settings. DESIGN: Retrospective observational cohort study. SETTING: Two academically affiliated Department of Veterans Affairs Medical Centers. SUBJECTS: Two hundred randomly selected patients at least 50 years old and receiving care at outpatient medical clinics. MAIN OUTCOME MEASURE: Frequency of documented skin examinations, in comparison with other tests routinely done as screening, during a 2-year period. METHODS: Medical record review to identify how often selected components of the physical examination and specific procedures were documented during ambulatory visits. RESULTS: Among the 200 subjects, the frequency of documented examinations and procedures included fecal occult blood testing in 120 (60%), rectal examination in 128 (64%), and sigmoidoscopy in 93 (47%), prostate examination was performed in 114 (59%) of 193 men. In contrast, skin examination was documented in only 56 (28%) of 200 subjects (P < .001 for each comparison with other tests). As an estimate of the "true" frequency of screening for skin cancer, 35 (18%) of 165 patients without skin-related complaints had a documented skin examination. CONCLUSION: Skin cancer screening is infrequently documented and therefore possibly omitted in the context of primary care visits.

Aged↗
PubMed1996

Factors associated with successful implantation of nonthoracotomy defibrillation lead systems.

Two hundred forty-three consecutive patients underwent attempted implantation of nonthoracotomy defibrillation lead (NTL) systems. The importance of clinical and lead-related factors were analyzed regarding their relation with implantation failure caused by an unacceptably high defibrillation threshold (DFT). Overall, 33 (14%) of 243 patients failed NTL implantation. Patients undergoing attempted implantation of NTL systems with monophasic shock waveforms (monophasic group, n = 145) had an incidence of failed implantation of 22% (n = 32) versus an incidence of 1% (n = 1) among patients undergoing attempted implantation by using biphasic shock waveforms (biphasic group, n = 98; odds ratio, 26.9; p < 0.001). The incidence of success and simplicity of implantation of NTL systems was markedly improved in patients undergoing NTL implantation by using biphasic shock waveforms. Clinical factors could be used to stratify patients in the monophasic group for their risk of implantation failure. In the biphasic group, no clinical factor could be correlated with a low DFT with a fully endovascular system.

Aged↗
PubMed1996

A simulation study of the number of events per variable in logistic regression analysis.

We performed a Monte Carlo study to evaluate the effect of the number of events per variable (EPV) analyzed in logistic regression analysis. The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality; the number of events per predictive variable was (252/7 =) 36 for the full sample. For the simulations, at values of EPV = 2, 5, 10, 15, 20, and 25, we randomly generated 500 samples of the 673 patients, chosen with replacement, according to a logistic model derived from the full sample. Simulation results for the regression coefficients for each variable in each group of 500 samples were compared for bias, precision, and significance testing against the results of the model fitted to the original sample. For EPV values of 10 or greater, no major problems occurred. For EPV values less than 10, however, the regression coefficients were biased in both positive and negative directions; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients; the 90% confidence limits about the estimated values did not have proper coverage; the Wald statistic was conservative under the null hypothesis; and paradoxical associations (significance in the wrong direction) were increased. Although other factors (such as the total number of events, or sample size) may influence the validity of the logistic model, our findings indicate that low EPV can lead to major problems.

Bias↗
PubMed1996

Muscle cramps in patients with cirrhosis.

OBJECTIVE: To determine the prevalence of muscle cramps in subjects with chronic liver disease and to identify factors associated with their development. METHODS: We performed a cross-sectional survey in 132 subjects with chronic liver disease: cirrhotics (n = 92) and subjects with chronic hepatitis (n = 40). In addition, to control for diuretic use, patients with congestive heart failure (n = 40) were included as a comparison group. RESULTS: The prevalence of chronic muscle cramps was significantly greater in cirrhotics compared with patients with chronic hepatitis [48/92 (52%) vs 3/40 (7.5%), respectively, p < 0.0001] and compared with subjects with congestive heart failure [8/40 (20%), p < 0.001]. Factors, including age, gender, alcoholic liver disease, electrolytes, and diuretic use were similar among cirrhotics with and without cramps. Significantly higher total bilirubin and lower albumin levels were noted in cirrhotics with and without cramps, respectively; however, there was no significant difference in Child's A or B classification. CONCLUSIONS: There is an increased prevalence of chronic muscle cramps in subjects with cirrhosis that appears to be independent of the etiology of cirrhosis, diuretic consumption, serum electrolyte alterations, or differences in Child's classification. These results suggest that cramps in these patients are related specifically to the development of cirrhosis, and worsening liver function may be a risk factor for the development of cramps.

Adult↗
PubMed1996

Importance of cerebrovascular disease in studies of myocardial infarction.

BACKGROUND AND PURPOSE: Myocardial infarction and stroke are both predominantly manifestations of atherosclerosis, yet stroke is commonly ignored in prognostic studies and therapeutic trials of ischemic heart disease. Our objective was to assess, in a community setting, the relative importance of stroke among patients at high risk for myocardial infarction. METHODS: We analyzed 1985 survey data from the National Academy of Science Twin Registry of white male veterans. To minimize confounding by genetic and environmental factors, we restricted our analysis to the rates of stroke and myocardial infarction among monozygotic twins counted as individuals or as twin pairs. RESULTS: Among 2764 monozygotic twins aged 58 to 68 years, the overall rate of myocardial infarction was 10% and stroke 3.1%. Among 2632 individual monozygotic twins (95%) with complete responses, the rate of stroke among men with a history of myocardial infarction was 7.5% (17/228) compared with 2.4% (58/2404) among those without myocardial infarction (odds ratio = 3.3, chi square 2 = 19.1, P<.001). A strong association between stroke and myocardial infarction was also found when the data were analyzed for twin pairs (chi square 2 = 135, P<.0005). CONCLUSIONS: Our results suggest that stroke, in addition to myocardial infarction, should be considered as an outcome in clinical investigations of ischemic heart disease.

Aged↗
PubMed1995

Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates.

The analytical effect of the number of events per variable (EPV) in a proportional hazards regression analysis was evaluated using Monte Carlo simulation techniques for data from a randomized trial containing 673 patients and 252 deaths, in which seven predictor variables had an original significance level of p < 0.10. The 252 deaths and 7 variables correspond to 36 events per variable analyzed in the full data set. Five hundred simulated analyses were conducted for these seven variables at EPVs of 2, 5, 10, 15, 20, and 25. For each simulation, a random exponential survival time was generated for each of the 673 patients, and the simulated results were compared with their original counterparts. As EPV decreased, the regression coefficients became more biased relative to the true value; the 90% confidence limits about the simulated values did not have a coverage of 90% for the original value; large sample properties did not hold for variance estimates from the proportional hazards model, and the Z statistics used to test the significance of the regression coefficients lost validity under the null hypothesis. Although a single boundary level for avoiding problems is not easy to choose, the value of EPV = 10 seems most prudent. Below this value for EPV, the results of proportional hazards regression analyses should be interpreted with caution because the statistical model may not be valid.

Computer Simulation↗