Biomedical subjects

Christopher S Coffey

Publications and source records attributed to Christopher S Coffey.

27 records · Page 2Linked to original sources

PubMed2002

Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction.

CONTEXT: beta-Blocker therapy remains substantially underused in cardiac patients despite its proven mortality benefits. Reluctance to prescribe these agents may derive from concerns about their association with symptoms of depression, fatigue, and sexual dysfunction. OBJECTIVE: To determine the association of beta-blockers with depressive symptoms, fatigue, and sexual dysfunction by performing a quantitative review of randomized trials that tested beta-blockers in myocardial infarction, heart failure, and hypertension. DATA SOURCES: Randomized trials of beta-blockers used in the treatment of myocardial infarction, heart failure, or hypertension were identified by searching the MEDLINE database for English-language articles (1966-2001). In addition, we searched the reference lists of previously published trials and reviews of beta-blockers for additional studies. STUDY SELECTION: Criteria for inclusion of trials in the review were: random allocation of study treatments, placebo control, noncrossover design, enrollment of at least 100 patients, and a minimum of 6 months of follow-up. The initial search produced 475 articles, 42 of which met these criteria. Fifteen of these trials reported on depressive symptoms, fatigue, or sexual dysfunction and were selected for inclusion. DATA EXTRACTION: For each trial, 1 author abstracted the frequency of adverse events in the beta-blocker and placebo groups and the numbers of patients randomized to the treatment groups. Two other authors verified the counts of events, and all authors adjudicated any discrepancies. Two different types of information on adverse events were abstracted: patient-reported symptoms and withdrawal of therapy due to a specified symptom. We categorized the tested beta-blockers by generation (early vs late) and lipid solubility (high vs low to moderate). DATA SYNTHESIS: The 15 trials involved more than 35,000 subjects. beta-Blocker therapy was not associated with a significant absolute annual increase in risk of reported depressive symptoms (6 per 1000 patients; 95% confidence interval [CI], -7 to 19). beta-Blockers were associated with a small significant annual increase in risk of reported fatigue (18 per 1000 patients; 95% CI, 5-30), equivalent to 1 additional report of fatigue for every 57 patients treated per year with beta-blockers. beta-Blockers were also associated with a small, significant annual increase in risk of reported sexual dysfunction (5 per 1000 patients; 95% CI, 2-8), equivalent to one additional report for every 199 patients treated per year. None of the risks of adverse effects differed significantly by degree of beta-blocker lipid solubility. The risk associated with reported fatigue was significantly higher for early-generation than for late-generation beta-blockers (P =.04). CONCLUSION: The conventional wisdom that beta-blocker therapy is associated with substantial risks of depressive symptoms, fatigue, and sexual dysfunction is not supported by data from clinical trials. There is no significant increased risk of depressive symptoms and only small increased risks of fatigue and sexual dysfunction. The risks of these adverse effects should be put in the context of the documented benefits of these medications.

Adrenergic beta-Antagonists↗

PubMed2002

Changes in antibiotic prescribing for children after a community-wide campaign.

CONTEXT: Overuse of antibiotics has contributed to microbial resistance, compromising the treatment of bacterial infections. Very high levels (>50%) of antibiotic resistance among invasive Streptococcus pneumoniae have been documented in Knox County, Tennessee. OBJECTIVE: To determine the effectiveness of a community-wide intervention aimed at reducing inappropriate antibiotic use among children. DESIGN, SETTING, AND PARTICIPANTS: The Knox County Health Department led a multifaceted year-long campaign (May 1997 through April 1998) aimed at decreasing unnecessary antibiotic use among children. Tennessee's 3 other major urban counties (Shelby, Hamilton, and Davidson) did not conduct similar campaigns and served as controls. Evaluation included white and black children (aged <15 years) enrolled in Tennessee's Medicaid Managed Care Program in the 4 study counties, representing 36% of the study counties' children (464 200 person-years observed). INTERVENTION: Educational efforts were directed toward health care practitioners (primarily via peer leader presentations) and to the parents of young children and the public (primarily via printed materials). MAIN OUTCOME MEASURE: The intervention-attributable effect on antibiotic use, defined as the excess percentage change in oral antibiotic prescription rates in Knox County between the 12-month preintervention and postintervention periods, relative to that of control counties. RESULTS: Antibiotic prescription rates declined 19% and 8% among Knox County and control county children, respectively, yielding an 11% intervention-attributable decline (95% confidence interval, 8%-14%; P<.001). The intervention-attributable decrease in prescription rates was greatest among children aged 1 to less than 5 years (among white children, 8% [P<.001]; among black children, 18% [P<.001]). CONCLUSIONS: A community-wide educational intervention reduced antibiotic prescription levels among children in Knox County.

Adolescent↗

PubMed2002

Winter viruses: influenza- and respiratory syncytial virus-related morbidity in chronic lung disease.

BACKGROUND: Chronic lung disease predisposes to serious consequences of respiratory viruses. While increasing influenza immunization rates in older adults signals an awareness of the impact of influenza, children with asthma are infrequently immunized. While respiratory syncytial virus (RSV) is recognized as an important target of vaccine development for infants, its impact on adults is underappreciated. METHODS: We performed a retrospective cohort study to estimate rates of hospitalizations, deaths, outpatient visits, and antibiotic courses due to influenza and RSV in persons with chronic lung disease in the Tennessee Medicaid program from 1995 to 1999. Differences between study event rates when influenza was cocirculating with RSV and event rates when RSV was circulating alone were used to calculate influenza-attributable morbidity. Differences in rates when RSV was circulating alone and during summer months were calculated to assess the effect of RSV. RESULTS: Influenza- and RSV-associated hospitalizations were highest at the extremes of age. There were an estimated 8 and 23 hospitalizations per 1000 children younger than 5 years annually due to influenza and RSV, respectively. There were 23 and 18 hospitalizations, as well as 2 and 5 deaths per 1000 persons 65 years or older annually due to influenza and RSV, respectively. Both viruses were associated with an excess of outpatient visits in children, and antibiotic prescriptions in all age groups. CONCLUSION: Among persons with chronic lung disease, influenza virus and RSV accounted for 15% to 33% of acute respiratory hospitalizations in children, 7% to 9% of such hospitalizations in adults, and 9% of deaths in those 65 years or older.

Adolescent↗

PubMed2002

Percent of cancer in the biopsy set predicts pathological findings after prostatectomy.

PURPOSE: The ability to use pretreatment variables to identify patients with organ confined prostate cancer continues to challenge physicians. We examined information available preoperatively, including prostate needle biopsy, clinical stage and preoperative prostate specific antigen (PSA), and evaluated these data based on pathological variables after radical retropubic prostatectomy. MATERIALS AND METHODS: We reviewed results in 135 consecutive patients who underwent radical retropubic prostatectomy at a single institution. Needle biopsy information, such as the number of cores, percent of tumor per biopsy set, laterality of positive cores and Gleason sum, were compared with pathological data on the radical retropubic prostatectomy specimen, including pathological stage, Gleason sum and tumor volume. Clinical data, including biopsy information and pathological findings, were compared using univariate and multivariate models. RESULTS: Overall total PSA, percent of tumor in the biopsy and bilateral positive cores directly correlated with tumor volume (p <0.01). Also, increasing PSA, increasing percent of tumor in the biopsy and bilateral positive cores were associated with increased risks of extracapsular extension (p <0.01). CONCLUSIONS: From the information readily available from prostate needle biopsy these results suggest that percent of tumor in the biopsy is a useful predictor of pathological stage and tumor volume. Furthermore, including percent of tumor in the biopsy set and bilateral disease with traditional variables such as serum PSA and clinical stage may improve pretreatment tumor staging. This finding adds additional credence to the inclusion of percent of tumor in the biopsy set in models for the preoperative prediction of pathological stage and should be factored into discussions with patients on treatment options.

Adult↗

PubMed2002

Two-stage testing in microarray analysis: what is gained?

Microarray technology for gene expression studies offers powerful new technology for understanding changes in gene expression as a function of other observable or manipulable variables. However, microarrays also pose a number of new challenges. One of the most prominent of these is the difficulty in establishing a procedure for declaring whether a gene's expression level is associated with the independent variable that offers reasonable and specifiable false-positive (type 1 error) and false-negative (type 2 error) rates. A recent article described a two-stage testing procedure to address these goals. However, information was not provided to indicate whether this procedure would or would not meet its objectives. Herein, we show mathematically that the two-stage procedure proposed does not provide benefits in terms of minimizing false-negatives while controlling the false-positive rate relative to standard single-stage testing. Therefore, investigators are encouraged to consider alternative analytic approaches.

Animals↗

PubMed2002

Health related quality of life assessment after radical cystectomy: comparison of ileal conduit with continent orthotopic neobladder.

PURPOSE: Health related quality of life after urinary diversion has been increasingly recognized as an important outcome measure. However, few studies have directly compared patients with an ileal conduit with those with a continent orthotopic neobladder and even fewer have used validated quality of life instruments. Therefore, we compared health related quality of life in patients who underwent neobladder versus ileal conduit creation using validated questionnaires. MATERIALS AND METHODS: We mailed 2 validated questionnaires that are measures of health related quality of life, namely the RAND 36-Item Health Survey (SF-36) and Functional Assessment of Cancer Therapy-General (FACT-G), to patients who underwent radical cystectomy for urothelial carcinoma between January 1995 and December 1999. Statistical analysis was performed, including univariate and multivariate analysis. RESULTS: A total of 112 patients were available for assessment. A total of 72 (64%) questionnaires were returned, including 23 (32%) and 49 (68%) from patients with an ileal conduit and neobladder, respectively. On the SF-36 questionnaire there were significant univariable relationships between treatment and age (p <0.001 and 0.01, respectively). Younger patients and those with a neobladder had higher health related quality of life scores, including significant differences in 5 of the 9 SF-36 domains (general health, physical functioning, physical health, social functioning and energy/fatigue). There was no relationship between health related quality of life and the final pathological stage (p = 0.25). On multivariate analysis adjusting for age led to a suggestive but nonsignificant difference in health related quality of life scores favoring neobladders (p = 0.09). On the FACT-G there were no significant differences in health related quality of life due to treatment (p = 0.28), pathological stage (p = 0.5), age (p = 0.72) or current disease status (p = 0.27). On the FACT-G 2 of the 4 domains (emotional and functional well-being) were significantly in favor of neobladders. Overall satisfaction was high in the 2 groups with 96% and 85% of patients with a neobladder and ileal conduit, respectively, reporting that they would make the same choice of diversion. CONCLUSIONS: Based on validated health related quality of life instruments these findings suggest that patients with an orthotopic neobladder have marginal quality of life advantages over those with an ileal conduit. However, differences in health related quality of life in the 2 types of urinary diversion are confounded by age since patients who underwent orthotopic diversion were younger and as a result of age would be expected to have a higher health related quality of life score. A prospective longitudinal study of health related quality of life after adjusting for differences in age among patients undergoing urinary diversion is currently underway to extend further these observations.

Aged↗

PubMed2002

Pathological parameters of radical prostatectomy for clinical stages T1c versus T2 prostate adenocarcinoma: decreased pathological stage and increased detection of transition zone tumors.

PURPOSE: Studies of radical prostatectomy specimens have suggested that the majority of prostate specific antigen detected (clinical stage T1c) tumors are clinically significant. We compared tumor location and pathological parameters in the radical prostatectomy specimens of stages T1c versus T2 cases in a 3-year period. The percent of stage T1c disease represented a stable majority of patients undergoing treatment for clinically localized prostate cancer. MATERIALS AND METHODS: From January 1, 1998 to December 31, 2000, 417 radical prostatectomies were performed at Vanderbilt University, including 246 for stage T1c and 108 for stage T2 disease. A total of 37 patients were excluded from study because of neoadjuvant antiandrogen treatment. Pathological parameters, including tumor location in the transition and/or peripheral zone, tumor Gleason grade, tumor stage, total tumor volume and surgical margins were compared in stages T1c and T2 cases, and in transition versus peripheral zone stage T1c tumors in completely embedded whole mount specimens. RESULTS: In contrast to stage T2 lesions, stage T1c tumors were of significantly lower Gleason score with a higher percent of Gleason score 5 and lower percent of Gleason score 6, 7 and 8 or greater. They also had a significantly smaller volume and lower pathological stage. Of stage T1c tumors 77% were organ confined versus 62% of stage T2 tumors. There was no statistically significant increase in clinically insignificant neoplasms in stages T1c versus T2 cases (13% versus 7%) when using a volume criterion of less than 0.2 cc but a statistically significant increase in clinically insignificant disease was observed using a volume criterion of less than 0.5 cc (22% versus 9%). Whereas none of the T2 tumors were located in the transition zone and 17% were located in the transition and peripheral zones, 14% of stage T1c lesions were exclusively in the transition zone, with another 17% in the transition and peripheral zones. Compared with peripheral zone tumors transition zone stage T1c tumors had a lower Gleason score with an increase in Gleason score 5 and lower percent of Gleason score 6, 7 and 8 or greater. Although transition zone stage T1c lesions were significantly larger than peripheral zone stage T1c lesions, they had a lower pathological stage with 94% versus 72% organ confined. CONCLUSIONS: Prostate specific antigen detected stage T1c tumors had a lower grade, stage and volume than stage T2 tumors during the same period. Lower tumor grade in stage T1c cases is due at least in part to the increased detection of Gleason pattern 2 containing transition zone tumors. Despite the larger size, T1c transition zone tumors appear to be more favorable with higher rates of organ confined and lower grade tumors. If such transition zone tumors prove to be biologically distinct, improved strategies to identify these lesions preoperatively may result in more conservative treatment recommendations.

Adenocarcinoma↗

PubMedDate not supplied

The free/total prostate-specific antigen ratio (%fPSA) is the best predictor of tumor involvement in the radical prostatectomy specimen among men with an elevated PSA.

BACKGROUND: The relationship between the free-to-total prostate-specific antigen ratio (%fPSA) and prostate cancer (CaP) pathology remains controversial. Previous reports have shown a direct correlation between %fPSA and prostate volume as well as an indirect correlation between %fPSA and unfavorable CaP pathology, particularly among men with an elevated PSA. We evaluated the use of %fPSA to predict CaP pathology including percent of tumor involvement in the radical prostatectomy (RP) specimen. METHODS: We prospectively analyzed 124 consecutive patients with CaP who underwent RP. In all patients, preoperative frozen serum was analyzed for assessment of %fPSA (Abbott Axsym). Pathologic review was performed using whole mount sections and total tumor volume was determined by planimetry. Statistical comparison between %fPSA and pathology was performed using log transformation. RESULTS: Percent fPSA was indirectly correlated with prostate volume in both the entire group (N=124) and among those patients (N=87) with a total PSA >4 ng/mL (P<0.001). Overall, both %fPSA and total PSA also correlated with total tumor volume (P=0.03 and P=0.01, respectively) and Gleason sum (P<0.001 and P<0.01). When we evaluated the percent of tumor involvement (tumor density) defined as the volume of tumor per gland divided by total gland volume, for the entire population, both total PSA and %fPSA were predictive with equal significance (P<0.001). However, among the subset of patients with a PSA>4.0 ng/mL, there was only a significant correlation between tumor density and %fPSA as compared to total PSA (P<0.001 vs. P=0.06, respectively). CONCLUSIONS: Independent of prostate volume, %fPSA is reflective of CaP pathology. Specifically, %fPSA was inversely correlated with tumor volume, Gleason sum and ECE. Among patients with modest PSA elevations, %fPSA was better than PSA in predicting percent of tumor involvement (tumor density) in the RP specimen.

Adult↗

PubMedDate not supplied

The confounding of race and geography: how much of the excess stroke mortality among African Americans is explained by geography?

INTRODUCTION: The excess stroke mortality among African Americans and Southerners is well known. Because a higher proportion of the population living in the 'Stroke Belt' is African American, then a portion of the estimated excess risk of stroke death traditionally associated with African-American race may be attributable to geography (i.e., race and geography are 'confounded'). In this paper we estimate the proportion of the excess stroke mortality among African Americans that is attributable to geography. METHODS: The numbers of stroke deaths at the county level are available from the vital statistics system of the US. A total of 1,143 counties with a population of at least 500 whites and 500 African Americans were selected for these analyses. The black-to-white stroke mortality ratio was estimated with and without adjustment for county of residence for those aged 45-64 and for those aged 65 and over. The difference in the stroke mortality ratio before versus after adjustment for county provides an estimate of the proportion of the excess stroke mortality inappropriately attributed to race (that is in fact attributable to geographic region). RESULTS: For ages 45-64, the black-to-white stroke mortality ratio was reduced from 3.41 to 3.04 for men, and from 2.82 to 2.60 for women, suggesting that between 10 and 15% of the excess mortality traditionally attributed to race is rather due to geography. Over the age of 65, the black-to-white stroke mortality ratio was reduced from 1.31 to 1.27 for men, and from 1.097 to 1.095 for women, suggesting that between 2 and 13% of the excess mortality attributed to black race is actually attributable to geography. The reductions of all the four age strata gender groups were highly significant. DISCUSSION: These results suggest that a significant, although relatively small, proportion of the excess mortality traditionally attributed to race is rather a factor of geography.

Age Factors↗