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Biomedical subjects

J C Cappelleri

Publications and source records attributed to J C Cappelleri.

At least 19 recordsLinked to original sources
PubMed1999

Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function.

OBJECTIVES: To evaluate the erectile function (EF) domain of the International Index of Erectile Function (IIEF) as a diagnostic tool to discriminate between men with and without erectile dysfunction (ED) and to develop a clinically meaningful gradient of severity for ED. METHODS: One thousand one hundred fifty-one men (1035 with and 116 without ED) who reported attempting sexual activity were evaluated using data from four clinical trials of sildenafil citrate (Viagra) and two control samples. The statistical program Classification and Regression Trees was used to determine optimal cutoff scores on the EF domain (range 6 to 30) to distinguish between men with and without ED and to determine levels of ED severity on the EF domain using the IIEF item on sexual intercourse satisfaction. RESULTS: For a 0.5 prevalence rate of ED, the optimal cutoff score was 25, with men scoring less than or equal to 25 classified as having ED and those scoring above 25 as not having ED (sensitivity 0.97, specificity 0.88). Sensitivity analyses revealed a robust statistical solution that was well supported with different assumed prevalence rates and several cross-validations. The severity of ED was classified into five categories: no ED (EF score 26 to 30), mild (EF score 22 to 25), mild to moderate (EF score 17 to 21), moderate (EF score 11 to 16), and severe (EF score 6 to 10). Substantial agreement was shown between these predicted and "true" classes (weighted kappa 0.80). CONCLUSIONS: The EF domain possesses favorable statistical properties as a diagnostic tool, not only in distinguishing between men with and without ED, but also in classifying levels of ED severity. Clinical validation with self-rated assessments of ED severity is warranted.

Erectile Dysfunction↗
PubMed1999

Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction.

An abridged five-item version of the 15-item International Index of Erectile Function (IIEF) was developed (IIEF-5) to diagnose the presence and severity of erectile dysfunction (ED). The five items selected were based on ability to identify the presence or absence of ED and on adherence to the National Institute of Health's definition of ED. These items focused on erectile function and intercourse satisfaction. For 1152 men (1036 with ED, 116 controls) analyzed, a receiver operating characteristic curve indicated that the IIEF-5 is an excellent diagnostic test. Based on equal misclassification rates of ED and no ED, a cutoff score of 21 (range of scores, 5-25) discriminated best (sensitivity=0.98, specificity=0. 88). ED was classified into five severity levels, ranging from none (22-25) through severe (5-7). Substantial agreement existed between the predicted and 'true' ED classes (weighted kappa=0.82). These data suggest that the IIEF-5 possesses favorable properties for detecting the presence and severity of ED.

Coitus↗
PubMed1999

Antipsychotic-induced weight gain: a comprehensive research synthesis.

OBJECTIVE: The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight. METHOD: A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. RESULTS: Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Insufficient data were available to evaluate quetiapine at 10 weeks. CONCLUSIONS: Both conventional and newer antipsychotics are associated with weight gain. Among the newer agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least. The differences among newer agents may affect compliance with medication and health risk.

Antipsychotic Agents↗
PubMed1999

The distribution of body mass index among individuals with and without schizophrenia.

OBJECTIVE: The objective of this study was to estimate and compare the distributions of body mass index (BMI: kg/m2) among individuals with and without schizophrenia, and, thereby, place the weight gain-inducing effects of antipsychotic drugs into context. METHOD: Data sources were (1) the mental health supplement of the 1989 National Health Interview Survey (NHIS; N = 80,130 nonschizophrenic and 150 self-reported schizophrenic individuals), (2) baseline BMI data from a drug trial of the anti-psychotic ziprasidone supplied by Pfizer Inc (420 noninstitutionalized individuals with chronic psychotic disorders [DSM-IV schizophrenia or schizoaffective disorder]) and (3) data from the National Health and Nutrition Examination Survey III (NHANES III; N = 17,689 nonschizophrenic individuals) to act as a control group for the ziprasidone trial data. RESULTS: After age-adjusting BMI in each data set, the NHIS data revealed that men with schizophrenia have mean BMIs similar to those of men without schizophrenia (26.14 vs. 25.63, respectively). In contrast, women with schizophrenia in the NHIS data set had a significantly (p<.001) higher mean BMI than did women without schizophrenia (27.36 vs. 24.50, respectively). Moreover, each decile was higher for women with schizophrenia than for women without schizophrenia. Analysis of the ziprasidone and NHANES III data sets revealed that, on average, men with schizophrenia have mean BMIs comparable to those of men without schizophrenia (26.79 vs. 26.52, respectively). In these 2 data sets, women with schizophrenia also had a mean BMI similar to those of women without schizophrenia (27.29 vs. 27.39, respectively). CONCLUSION: Although there may be a small subpopulation of schizophrenic individuals who are underweight, individuals with schizophrenia were, on the whole, as obese as or more obese than individuals without schizophrenia, suggesting that weight gain induced by antipsychotic agents is an important concern for many individuals.

Antipsychotic Agents↗
PubMed1998

An empirical study of the effect of the control rate as a predictor of treatment efficacy in meta-analysis of clinical trials.

If the control rate (CR) in a clinical trial represents the incidence or the baseline severity of illness in the study population, the size of treatment effects may tend to very with the size of control rates. To investigate this hypothesis, we examined 115 meta-analyses covering a wide range of medical applications for evidence of a linear relationship between the CR and three treatment effect (TE) measures: the risk difference (RD); the log relative risk (RR), and the log odds ratio (OR). We used a hierarchical model that estimates the true regression while accounting for the random error in the measurement of and the functional dependence between the observed TE and the CR. Using a two standard error rule of significance, we found the control rate was about two times more likely to be significantly related to the RD (31 per cent) than to the RR (13 per cent) or the OR (14 per cent). Correlations between TE and CR were more likely when the meta-analysis included 10 or more trials and if patient follow-up was less than six months and homogeneous. Use of weighted linear regression (WLR) of the observed TE on the observed CR instead of the hierarchical model underestimated standard errors and overestimated the number of significant results by a factor of two. The significant correlation between the CR and the TE suggests that, rather than merely pooling the TE into a single summary estimate, investigators should search for the causes of heterogeneity related to patient characteristics and treatment protocols to determine when treatment is most beneficial and that they should plan to study this heterogeneity in clinical trials.

Humans↗
PubMed1998

Issues in comparisons between meta-analyses and large trials.

CONTEXT: The extent of concordance between meta-analyses and large trials on the same topic has been investigated with different protocols. Inconsistent conclusions created confusion regarding the validity of these major tools of clinical evidence. OBJECTIVE: To evaluate protocols comparing meta-analyses and large trials in order to understand if and why they disagree on the concordance of these 2 clinical research methods. DESIGN: Systematic comparison of protocol designs, study selection, definitions of agreement, analysis methods, and reported discrepancies between large trials and meta-analyses. RESULTS: More discrepancies were claimed when large trials were selected from influential journals (which may prefer trials disagreeing with prior evidence) than from already performed meta-analyses (which may target homogeneous trials) and when both primary and secondary (rather than only primary) end points were considered. Depending on how agreement was defined, kappa coefficients varied from 0.22 (low agreement) to 0.72 (excellent agreement). The correlation of treatment effects between large trials and meta-analyses varied from -0.12 to 0.76, but was more similar (0.50-0.76) when only primary end points were considered. When both the magnitude and uncertainty of treatment effects were considered, large trials disagreed with meta-analyses 10% to 23% of the time. Discrepancies were attributed to different disease risks, variable protocols, quality, and publication bias. CONCLUSIONS: Comparisons of large trials with meta-analyses may reach different conclusions depending on how trials and meta-analyses are selected and how end points and agreement are defined. Scrutiny of these 2 major research methods can enhance our appreciation of both for guiding medical practice.

Bias↗
PubMed1997

Correlation of biochemical response to interferon alfa with histological improvement in hepatitis C: a meta-analysis of diagnostic test characteristics.

The current goal of interferon treatment for chronic hepatitis C is to normalize alanine aminotransferase (ALT) and to eradicate detectable viral RNA. Many patients do not achieve this objective during treatment, and most do not sustain these outcomes after interferon is discontinued. However, biochemical or virological responses to interferon may not reflect accurately the histological consequences of therapy. The aim of this study was to determine the extent to which the biochemical measures reflect the histological outcomes in the treatment of hepatitis C with interferon alfa using a meta-analysis of diagnostic test characteristics. The data sources were English and non-English language studies retrieved from Medline (from 1966 to December 1995). The study selection included studies in which interferon alfa was used for treatment of chronic hepatitis C with liver biopsies performed before and after therapy. Data on histological and biochemical outcomes were extracted independently by two reviewers. Two separate criteria were used for defining histological response. When strict definitions of histological improvement were considered, histology improved in 28% (95% confidence interval [95% CI], 17%-43%) of patients after interferon treatment. The sensitivity and specificity of the ALT for determining histological change were 70% (95% CI, 56%-81%) and 66% (95% CI, 56%-75%), respectively. As many as 17% (95% CI, 9%-30%) of subjects with an abnormal ALT at the end of therapy may have improved histologically after interferon therapy. When less stringent definitions of histological improvement were considered, 62% (95% CI, 51%-72%) improved after therapy. The sensitivity and specificity of the ALT for determining histological change were 55% (95% CI, 44%-65%) and 75% (95% CI, 67%-81%), respectively. As many as 51% (95% CI, 38%-64%) may have improved, despite failure to normalize ALT. A substantial number of patients may improve histologically after interferon therapy. The significance of histological changes observed after interferon therapy must be weighed against the limitations of liver biopsy and the uncertain natural history of hepatitis C. Nevertheless, the ALT does not always reflect liver histology accurately after interferon alfa treatment and may underestimate histological improvement.

Alanine Transaminase↗
PubMed1997

The relationship between study design, results, and reporting of randomized clinical trials of HIV infection.

We examined whether the study design of randomized clinical trials for medications against human immunodeficiency virus (HIV) may affect the results and whether the outcomes of these trials affect reporting and publication. We used a database of 71 published randomized HIV-related drug efficacy trials and considered the following study design factors: endpoint definition and method of analysis, masked design, sample size, and duration of follow-up. Large variation was noted in the methods of analysis for surrogate endpoints. Often statistical significance for a surrogate endpoint was not associated with statistical significance for the clinical endpoint or for survival in the same trial, although disagreements in the direction of the treatment effect for surrogate endpoints and survival within individual trials were uncommon. Open-label design seemed to affect the magnitude of the treatment effect for two treatments. The magnitude of the treatment effect in trials of zidovudine monotherapy was inversely related to their sample size, but this probably reflected the confounding effect of longer duration of follow-up in large trials (with a resulting loss of efficacy) rather than publication bias. There was, however, evidence for potential bias in reporting and publication of HIV-related trials. Meta-analyses of published trials for specific treatments demonstrated a sizable treatment benefit for all the examined medications regardless of whether these medications were officially approved, controversial, or abandoned, raising concerns about either publication bias or unjustifiable rejection of potentially useful medications. Compared with trials published in specialized journals, trials published in journals of wide readership were larger (p = 0.001) and 4.4 times more likely to report "positive" results (p = 0.01). We identified several examples of trials with "negative" results that have remained unpublished for a long time. In conclusion, study design factors may have an impact on the magnitude and significance of the treatment effect in HIV-related trials. Bias in reporting can further affect the information that these studies provide.

Anti-HIV Agents↗
PubMed1996

Impact of epidemic and individual heterogeneity on the population distribution of disease progression rates. An example from patient populations in trials of human immunodeficiency virus infection.

Patients at the same stage of chronic disease may have had different rates of disease progression. The authors developed a mathematical modeling approach that allows reconstructing and comparing populations in terms of the disease progression rates of their participants when the disease onset and progression rates are unknown for individual patients. Human immunodeficiency virus 1 infection was used as an example. Both published and hypothetical models were used to describe the human immunodeficiency virus 1 epidemic (epidemic heterogeneity) and incubation and survival functions for different disease stages (individual heterogeneity). Reconstructions of populations with late disease (e.g., acquired immunodeficiency syndrome patients) show a marked predominance of rapid progressors, unless the incidence of new infections has been decreasing for a long time. Rapid progressors would also predominate in populations of acute seroconverters, unless diagnosis is based on repeated serologic screening rather than symptoms. Populations of patients who have not progressed beyond an early stage of the disease (e.g., patients with CD4 cell counts > 500/microliter) tend to overrepresent slow progressors, especially if the epidemic has been decreasing for a long time. With this approach, one can assess whether the target population of a clinical trial is comparable with other patient populations at different places and times. Epidemic and individual diversity may even affect trial results if patients with different progression rates experience different benefits from a treatment. By modeling the targeted populations in trials of early versus deferred antiretroviral treatment, the authors observed larger treatment benefits in trials in which rapid progressors probably predominated, compared with trials of slow progressors.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Single or multiple daily doses of aminoglycosides: a meta-analysis.

OBJECTIVE: To assess relative efficacy and toxicity of aminoglycosides given by single daily dose compared with multiple daily doses. DESIGN: Meta-analysis of 21 randomised trials identified through MEDLARS (1966 to January 1995). Data were overviewed with fixed effects and random effects models and with meta-regression analysis. SUBJECTS: Total of 3091 patients with bacterial infection, most without pre-existing renal disease. INTERVENTIONS: Patients were randomized to receive aminoglycosides once daily or multiple times daily with similar total daily dose. MAIN OUTCOME MEASURES: Clinical failure of treatment, nephrotoxicity, ototoxicity, and mortality. RESULTS: Single daily dose regimen produced a non-significant decrease in risk of antibiotic failures (random effects risk ratio 0.83 (95% confidence interval 0.57 to 1.21)). Benefit of once daily dosing was greater when the percentage of pseudomonas isolates in a trial was larger. Once daily administration reduced risk of nephrotoxicity (fixed effects risk ratio 0.74 (0.54 to 1.00)). Similar trends were noted for patients with febrile neutropenia and for children. There was no significant difference in ototoxicity between the two dosing regimens, but the power of the pooled trials to detect a meaningful difference was low. There was no significant difference in mortality. CONCLUSIONS: Once daily administration of aminoglycosides in patients without pre-existing renal impairment is as effective as multiple daily dosing, has a lower risk of nephrotoxicity, and no greater risk of ototoxicity. Given the additional convenience and reduced cost, once daily dosing should be the preferred mode of administration.

Aminoglycosides↗
PubMed1996

A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens.

BACKGROUND: Finding the optimal strategy for Pneumocystis carinii prophylaxis in patients with human immunodeficiency virus infection can be problematic. Several prophylactic regimens are available, but their relative efficacy and tolerance are not well understood. METHODS: A meta-analysis overviewed 35 randomized trials comparing different regimens for P carinii prophylaxis directly or with placebo. Analyses were based on intention-to-treat. On-treatment data were also analyzed when available. RESULTS: Regardless of dose, sulfamethoxazole-trimethoprim was almost universally effective for patients who tolerated it. The risk of discontinuing sulfamethoxazole-trimethoprim because of side effects decreased by 43% (95% confidence interval, 30% to 54%) if one double-strength tablet was given three times a week instead of daily. For dapsone, among 100 patients given 100 mg daily instead of twice a week for 1 year (primary prophylaxis), seven fewer patients would develop P carinii pneumonia, but 17 more would have significant toxic reactions. Aerosolized pentamidine was well tolerated regardless of the dose used. Prophylaxis failures might be halved if the dose of aerosolized pentamidine were doubled. Compared with aerosolized pentamidine, oral regimens prevented 73% (95% confidence interval, 57% to 82%) of toxoplasmosis events by on-treatment analysis, but only 33% (95% confidence interval, 12% to 50%) by intention-to-treat. No significant difference in mortality was demonstrated between different regimens. CONCLUSIONS: Sulfamethoxazole-trimethoprim is the superior regimen, and low doses could improve tolerance without losing effectiveness for primary prophylaxis. Low doses of dapsone reduce toxic effects, but at the expense of some loss of efficacy. There are few data on the use of low-dose regimens for secondary prophylaxis. High doses of aerosolized pentamidine may improve the efficacy of this regimen. Aerosolized pentamidine is inadequate for prevention of toxoplasmosis, and strategies that improve the tolerance of oral regimens may increase effectiveness in preventing toxoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Predictive value of viral load measurements in asymptomatic untreated HIV-1 infection: a mathematical model.

OBJECTIVE: To model the predictive value of viral load measurements in asymptomatic patients with HIV-1 infection, who have CD4 cell counts > 500 x 10(6)/l and no prior antiretroviral therapy, when the time of seroconversion and the prior levels of viremia are unknown. DESIGN: A mathematical model was constructed for the changes in HIV RNA load over time based on data from cohorts of HIV-infected patients followed since the time of seroconversion. METHODS: For different values of viral load, the time to progression to AIDS or an equivalent state [progression to AIDS equivalent (PAE)] was calculated using a wide range of estimates for the time since seroconversion and the rate of change of the viral load over time. RESULTS: In the absence of antiretroviral treatment, patients with a viral load of 10(5) copies/ml serum are at risk for PAE in less than 3 years (0-3 years) and patients with a viral load half a log higher are at risk in less than 1 year. In contrast, patients with a viral load of 10(4.5) have at least 1.9 years and may have up to 8 years before risk of PAE. Patients with a viral load of 10(4) RNA copies/ml have at least 2.8 years and may have up to 19 years before risk of PAE. The rate of change of the viral load was an important predictor of outcome; the time since seroconversion had only a minor effect. CONCLUSIONS: The viral load in the plasma or serum has predictive value even if the time of seroconversion is unknown. The rate of change of viral load over time may also be an important predictive factor. Serial measurements of viral load over time may provide therapeutic guidance.

CD4 Lymphocyte Count↗
PubMed1995

Early or deferred zidovudine therapy in HIV-infected patients without an AIDS-defining illness.

PURPOSE: To do a meta-analysis on the efficacy of early or deferred zidovudine monotherapy in patients with human immunodeficiency virus (HIV) infection but not the acquired immunodeficiency syndrome (AIDS). DATA SOURCES: Articles on zidovudine monotherapy published through May 1994. STUDY SELECTION: Double-blind, randomized, placebo-controlled trials addressing the efficacy of zidovudine monotherapy in HIV-infected persons without an AIDS-defining illness. DATA EXTRACTION: Progression to any primary trial end point; any clinical end point; and AIDS or death. Data were stratified according to disease stage at study entry and duration of follow-up (short-term, < 14 months; long-term, > 21 months). DATA SYNTHESIS: Early initiation of zidovudine therapy was of short-term benefit for all the end points evaluated (for example, the risk ratio for progression to any primary end point was 0.51; 95% CI, 0.41 to 0.64). Long-term trials showed a marginally significant trend of decreased progression to any primary end point (risk ratio, 0.73; CI, 0.52 to 1.03). The trend was not significant for other end points. With further stratification according to disease stage, progression to AIDS or death in the short term was significantly decreased for both symptomatic and asymptomatic patients with CD4 cell counts of less than 500 x 10(6)/L (risk ratios, 0.26 [CI, 0.13 to 0.56] and 0.43 [CI, 0.30 to 0.64], respectively). A regression analysis indicated a larger relative benefit in short-term trials and symptomatic patients than in long-term trials and asymptomatic patients. CONCLUSIONS: Early initiation of zidovudine therapy offers a benefit that decreases over time. Symptomatic patients experience a larger benefit than asymptomatic patients. The implications beyond 3 years of follow-up remain unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Efficacy and safety of different aspirin dosages on vascular diseases in high-risk patients. A metaregression analysis.

PURPOSE: To compare the efficacy and safety of different aspirin dosages in trials with patients at increased risk of vascular disease. DATA SOURCES: Pertinent studies were selected using MEDLINE (1966 through 1992), weekly reviews of Current Contents (1970 through 1992), and references from review articles and editorials. STUDY SELECTION: Thirty-six randomized control trials of aspirin compared with another dosage of aspirin or with placebo. METHODS: The Mantel-Haenszel method of pooling odds ratios and metaregression involving log odds ratio (and the risk difference) on aspirin dosage, adjusting for the control rate and the mean length of follow up of the studies. RESULTS: For all patients and for subgroups of patients with previous vascular conditions, there was no relationship between dose and vascular events. For all patients, a dose-response relation was not found with gastrointestinal hemorrhages and hemorrhagic stroke, but was found with gastrointestinal symptoms and withdrawals from side effects. For every 25 mg/day increase in aspirin dosage, the odds ratio of gastrointestinal symptoms and withdrawals increased, respectively, by 0.87% (99% Cl, 0.18 to 1.57%) and 0.94% (99% Cl, 0.06 to 1.82%). The corresponding absolute risk increases were 0.58 and 0.78 per 1,000 patients. CONCLUSIONS: Direct and indirect comparisons of high-risk patients suggest no statistical differences in efficacy, gastrointestinal bleeds, and hemorrhagic strokes across aspirin dosages. These comparisons, however, suggest decreased risk of gastrointestinal symptoms and of withdrawals with lower doses of aspirin. More direct comparison studies are warranted that should contrast the benefits and risks to determine the net benefit.

Aspirin↗