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Biomedical subjects

Matthew P Fox

Publications and source records attributed to Matthew P Fox.

7 recordsLinked to original sources
PubMed2006

Failure of standard antimicrobial therapy in children aged 3-59 months with mild or asymptomatic HIV infection and severe pneumonia.

OBJECTIVE: To determine whether children aged 3-59 months with mild or non-symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe pneumonia have a higher failure rate than do HIV-uninfected children when treated with the standard WHO treatment of parenteral penicillin or oral amoxicillin. METHODS: This study was a planned sub-analysis of a randomized trial of 3-59-month-old children presenting with WHO-defined severe pneumonia (the APPIS study). We included two sites with high HIV prevalence in Durban, South Africa and Ndola, Zambia. Primary outcome measures were clinical treatment failure at day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER: CT00227331http://www.clinicaltrialsgov/show/NCT00227331). FINDINGS: Of the 523 children enrolled, HIV status was known for 464 participants; 106 (23%) of these were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and 110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day 2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected children failed treatment by day 14 compared with 76 (21.2%) uninfected children (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the greatest differential in treatment failure at day 2 and day 14 occurred in the children aged 3-5 months. CONCLUSIONS: HIV-infected children with severe pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin at day 2 and day 14 more often than do HIV-uninfected children, especially young infants. Standard case management of acute respiratory infection (ARI) using WHO treatment guidelines is inadequate in areas of high HIV prevalence and reappraisal of empiric antimicrobial therapy is urgently needed for severe pneumonia associated with HIV-1.

Amoxicillin↗
PubMed2006

Adherence to tamoxifen over the five-year course.

PURPOSE: To estimate the proportion of older women who fail to complete 5 years of tamoxifen therapy and to identify predictors of non-adherence. PATIENTS AND METHODS: We followed 462 women 65-years-old or older with stage I-IIIA breast cancer diagnosed in four US regions between 1996 and 1999 and who initiated tamoxifen therapy. We interviewed patients annually to assess tamoxifen adherence and collected information about predictors of adherence by medical record review, patient interview, and physician questionnaire. RESULTS: Thirty-one percent of patients who started tamoxifen failed to complete the recommended 5-year course. Patients who had initial severe side effects [hazard ratio (HR) per side effect=1.2, 95% confidence interval (CI) 0.97, 1.5] or developed them (HR per new side effect=1.3, 95% CI 1.0, 1.6) were more likely to discontinue. Patients with more prescription medications at baseline were less likely to discontinue (HR per baseline prescription equaled 0.90, 95% CI 0.81, 0.99), whereas patients who added a prescription were more likely to discontinue (HR per new prescription equaled 1.2, 95% CI 1.0, 1.4). Patients with positive views of tamoxifen at baseline (HR for a 10-point higher score=0.93, 95% CI 0.83, 1.0) and an improving view over follow-up (HR for a 10-point positive change=0.93, 95% CI 0.87, 1.0) were less likely to discontinue. CONCLUSION: Five years of tamoxifen confers a significant benefit beyond 1-2 years of tamoxifen, so physicians should ask patients about side effects, other prescriptions, and beliefs about tamoxifen and should educate them about the benefits of completing adjuvant therapy.

Aged↗
PubMed2005

A method to automate probabilistic sensitivity analyses of misclassified binary variables.

BACKGROUND: Misclassification bias is present in most studies, yet uncertainty about its magnitude or direction is rarely quantified. METHODS: The authors present a method for probabilistic sensitivity analysis to quantify likely effects of misclassification of a dichotomous outcome, exposure or covariate. This method involves reconstructing the data that would have been observed had the misclassified variable been correctly classified, given the sensitivity and specificity of classification. The accompanying SAS macro implements the method and allows users to specify ranges of sensitivity and specificity of misclassification parameters to yield simulation intervals that incorporate both systematic and random error. RESULTS: The authors illustrate the method and the accompanying SAS macro code by applying it to a study of the relation between occupational resin exposure and lung-cancer deaths. The authors compare the results using this method with the conventional result, which accounts for random error only, and with the original sensitivity analysis results. CONCLUSION: By accounting for plausible degrees of misclassification, investigators can present study results in a way that incorporates uncertainty about the bias due to misclassification, and so avoid misleadingly precise-looking results.

Bias↗
PubMed2005

A sensitivity analysis of a randomized controlled trial of zinc in treatment of falciparum malaria in children.

BACKGROUND: The randomized trial has long been recognized as a means to assess the efficacy of new interventions, because the investigator can reduce or eliminate many sources of error. As such, clinical trials often do not include quantitative assessments of the extent that systematic error could affect their results. We examined the impact of different sources of bias on a randomized controlled trial of the efficacy of zinc as an adjuvant to malaria therapy in reducing time to total parasite clearance. METHODS: Using data from a previously published study, we identified two sources of bias and used the sensitivity analysis technique developed by Lash and Fink to assess the impact of each source of bias on the outcome. RESULTS: After correcting for each source of bias and reincorporating random error into our results, the point estimate of effect comparing those who received placebo to those who received zinc changed slightly (SMR changed from 0.92 to 0.90) but the 95% interval increased 22% (changing from 0.73-1.16 in the conventional analysis to 0.65-1.26 in the sensitivity analysis). CONCLUSIONS: The findings of this sensitivity analysis serve as a reminder that the frequentist confidence interval underestimates the total error, even in a randomized controlled trial. Authors of randomized controlled trial investigations ought to conduct a complete assessment of the impact of potential sources of bias in their studies. CONSORT guidelines for reporting trial results should be updated to encourage authors to assess the impact of non-random errors on their studies.

Antimalarials↗
PubMed2004

The impact of HIV/AIDS on labour productivity in Kenya.

OBJECTIVES: To estimate the impact of HIV/AIDS on individual labour productivity during disease progression. METHODS: We used a retrospective cohort design to study the productivity and attendance of tea estate workers who died or were medically retired because of AIDS-related causes between 1997 and 2002 in western Kenya. We compared daily output in kilograms of tea leaves plucked, use of paid and unpaid leave and assignment to less strenuous tasks by 54 workers who died or were medically retired because of AIDS to those of comparison workers, matched on time and tea field using longitudinal regression. RESULTS: HIV-positive workers plucked less tea in the 18 months preceding AIDS-related termination and used more leave in the 3 years before termination. After adjusting for age and environmental factors, cases plucked between 4.11 and 7.93 kg/day less in the last year and a half before termination. Cases used between 9.2 and 11.0 more sick leave days, between 6.4 and 8.3 more annual leave days, between 19.9 and 11.8 more casual leave days, and spent between 19.2 and 21.8 more days doing less strenuous tasks in the 2 years before termination than did comparison pluckers. Tea pluckers who terminated because of AIDS-related causes earned 16.0% less in their second year before termination and 17.7% less in the year before termination. CONCLUSION: These results provide empirical estimates of the impact of HIV/AIDS on labour productivity. As workers often bring unrecorded 'helpers', actual differences may be greater. Decreased attendance and output may put sick workers in jeopardy of losing their jobs and impose financial burdens on employers.

Absenteeism↗
PubMedDate not supplied

Reduced mortality rate associated with annual mammograms after breast cancer therapy.

Guidelines have been developed for appropriate posttherapy surveillance for breast cancer recurrence. One purpose of posttherapy surveillance is to detect potentially curable local recurrences and new cancers in the opposite breast. The objective of this investigation was to assess the impact of annual mammography on all-cause mortality in breast cancer survivors. We conducted a case-control analysis nested in a cohort of 865 stage I or II breast cancer patients diagnosed from 1996 to 1999. The exposure variable was the number of mammograms received after completing primary therapy. Cases were decedents and we used risk-set sampling to match eight controls to each case on follow-up time. The mortality rate declined with an increasing number of mammograms (p for trend=0.007). The age- and therapy-adjusted odds ratio associating receipt of an additional mammogram, compared with receipt of no mammogram, equaled 0.77 (95% confidence interval [CI] 0.53-1.1). These results are consistent with a protective effect of regular surveillance mammography after completing therapy for early stage breast cancer.

Aged↗