Perceived susceptibility to developing cancer and mammography screening behaviour: a cross-sectional analysis of Alberta's Tomorrow Project.

OBJECTIVES: Cross-sectional data from Alberta's Tomorrow Project (ATP) were used to assess the association between perceived susceptibility (PS) to developing cancer and mammography screening behaviour. STUDY DESIGN: Cross-sectional study. METHODS: ATP participants between 35 and 70 years of age who reported being free of chronic conditions were included in the study (n = 1803). PS was measured using three variables: participants' estimate of their personal PS of developing cancer, compared to others, on a 5-point Likert scale; participants' estimate of the percentage of people in their age group who would be diagnosed with cancer; and participants' estimate of their own chance (expressed as a percentage) of being diagnosed with cancer. Multivariable logistic regression models, adjusting for age, marital status, work status, education, family history, and place of residence, were used to explore the association of interest. RESULTS: PS of developing cancer was modestly yet significantly associated with mammography screening behaviour for two of the three PS variables. Specifically, the adjusted odds of mammography screening were 1.20 times greater for each one-unit increase in personal PS of developing cancer (95% confidence interval [CI] = 1.07-1.36 [P = 0.003]) and 1.01 times greater for each one-unit increase in both participants' estimate of the percentage of people who would develop cancer (95% CI = 1.00-1.01 [P = 0.05]) and participants' estimate of their own chance of developing cancer (95% CI = 1.00-1.01 [P = 0.02]). CONCLUSIONS: Understanding how certain factors, such as PS, are associated with screening behaviour is important to help address the underutilization of cancer screening.

The association between antibiotic use in infancy and childhood overweight or obesity: a systematic review and meta-analysis.

PURPOSE: Antibiotic use is associated with alteration of the gut microbiome and metabolic activity. As childhood obesity is a predisposing factor for adult obesity, addressing childhood risk factors to weight gain in early life is important. This review aims to investigate the association between infant antibiotic exposure (aged < 24 months) and childhood obesity or overweight. METHODS: Articles were retrieved from CINAHL, Cochrane CENTRAL, Embase and MEDLINE. Eligible articles investigated antibiotic use in exposed versus unexposed infants and measured childhood weight change. Data were synthesized narratively and meta-analysed where possible. RESULTS: After title/abstract and full-text screening, 17 articles representing 15 unique studies were included for narrative synthesis. We found a small association between antibiotic exposure in infancy (<24 months) and childhood overweight or obesity. The strongest associations were observed in boys versus girls and children exposed to multiple antibiotic courses or broad-spectrum drugs. Meta-analysis of 12 sets of results comparing the earliest age of exposure to any antibiotic with overweight or obesity at the latest age of outcome found a pooled odds ratio of 1.05 (95% confidence interval: 1.00-1.11). CONCLUSIONS: Antibiotic exposure in infants, aged < 24 months, was associated with a small increase in odds of childhood overweight or obesity in some subgroups of children.

Testing for BNP and NT-proBNP in the diagnosis and prognosis of heart failure.

OBJECTIVES: The purpose of this systematic review was to evaluate BNP and NT-proBNP to: (a) identify determinants, (b) establish their diagnostic performance in heart failure (HF) patients, (c) determine their predictive ability with respect to mortality and other cardiac endpoints, and (d) determine their value in monitoring HF treatment. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Central, and AMED from 1989 to February 2005 were searched for primary studies. REVIEW METHODS: Standard systematic review methodology, including meta-analysis, was employed. All study designs were included. Eligibility criteria included English-only studies and restricted the number of test methods to maximize generalizability. Outcomes for prognosis were limited to mortality and specific cardiac events. Further specific criteria were developed for each research question. RESULTS: Determinants: There were 103 determinants identified including age, gender, disease, treatment, as well as biochemical and physiological measures. Few studies reported independent associations and of those that did age, female gender and creatinine levels were positively associated with BNP and NT-proBNP. DIAGNOSIS: Pooled sensitivity and specificity values were 94 and 66 percent for BNP and 92 and 65 percent for NT-proBNP; there was minimal difference among settings (emergency, specialized clinics, and primary care). B-type natriuretic peptides also added independent diagnostic information above traditional measures for HF. PROGNOSIS: Both BNP and NT-proBNP were found to be independent predictors of mortality and other cardiac composite endpoints in patients with risk of coronary artery disease (CAD) (risk estimate range = 1.10 to 5.40), diagnosed CAD (risk estimate range = 1.50 to 3.00), and diagnosed HF patients (risk estimate range = 2.11 to 9.35). With respect to screening, the AUC values (range = 0.57 to 0.88) suggested poor performance. Monitoring Treatment: Studies showed therapy reduced BNP and NT-proBNP, however, relationship to outcome was limited and not consistent. CONCLUSIONS: Determinants: The importance of the identified determinants for clinical use is not clear. DIAGNOSIS: In all settings both BNP and NT-proBNP show good diagnostic properties as a rule out test for HF. PROGNOSIS: BNP and NT-proBNP are consistent independent predictors of mortality and other cardiac composite endpoints for populations with risk of CAD, diagnosed CAD, and diagnosed HF. There is insufficient evidence to determine the value of B-type natriuretic peptides for screening of HF. Monitoring Treatment: There is insufficient evidence to demonstrate that BNP and NT-proBNP levels show change in response to therapies to manage stable chronic HF patients.

Clinical efficacy and safety of a short regimen of azithromycin sequential therapy vs standard cefuroxime sequential therapy in the treatment of community-acquired pneumonia: an international, randomized, open-label study.

An international, randomized, open-label, comparative study was undertaken in order to assess the efficacy and safety of azithromycin and cefuroxime, short sequential vs standard sequential therapy, respectively, in the treatment of patients with community-acquired pneumonia (CAP). 180 adult patients were included in the study. 89 patients received azithromycin 500 mg intravenously (i.v.) once daily for 1-4 days followed by azithromycin 500 mg orally once daily for 3 days. 91 patients received cefuroxime 1.5 g i.v. three times daily for 1-4 days followed by cefuroxime axetil 500 mg orally twice daily for 7 days. Clinical efficacy was achieved in 67/82 (81.7%) patients treated with azithromycin, and in 73/89 (82.0%) patients treated with cefuroxime. The mean duration of total (i.v. and oral) therapy was significantly shorter for the azithromycin group than for the cefuroxime group (6.2 days vs 10.1 days). Adverse events were recorded in 38.2% of patients treated with azithromycin, and in 29.7% of patients treated with cefuroxime (p = 0.20). Shorter sequential i.v.-to-oral azithromycin therapy of patients with CAP was as effective as standard sequential i.v.-to-oral cefuroxime therapy.

Interrater reliability of the modified Jadad quality scale for systematic reviews of Alzheimer's disease drug trials.

Drug therapies for Alzheimer's disease (AD) have been evaluated in clinical trials over the past 2 decades. Systematic reviews of AD drug trials can shed more light on the efficacy of pharmaceutical interventions. The modified Jadad scale can be used to assess the quality of trial reports that are candidates for inclusion in these systematic reviews. The interrater reliability of the modified Jadad scale was examined during such a review. Three blinded reviewers rated the quality of 42 AD drug trial reports: the intraclass correlation coefficient was 0.90. The modified Jadad scale appears to be a useful tool for AD research because of the very good interrater reliability. Also, it is composed of items that are well suited to the specific disease characteristics of AD. Further research should focus on the validity of this instrument.

Review of outcome measurement instruments in Alzheimer's disease drug trials: introduction.

This article introduces a four-part series on outcome scales used in Alzheimer's disease drug trials. First, it discusses the division of scales into four domains: cognition, functional ability/quality of life, behavior/mood, and global. Within each domain, the shortcomings of existing literature reviews are outlined, and the need for a more coherent view of the psychometric properties of the scales is emphasized. Second, the key concepts of reliability, validity, and responsiveness to change are defined and explained. This explanation also provides an overview of the statistical techniques used to assess measurement properties. Finally, the methods used to select the scales for review in the subsequent articles are explained, and each article is briefly introduced.

Review of outcome measurement instruments in Alzheimer's disease drug trials: psychometric properties of functional and quality of life scales.

The psychometric properties of functional and quality of life outcome measures that were used for the purpose of showing changes in antidementia drug trials for Alzheimer's disease are described and critiqued. The seven functional scales reviewed for reliability, validity, and responsiveness to change included the Geriatric Evaluation by Relative's Rating Instrument, the Physical Self-Maintenance Scale, the Instrumental Activities of Daily Living, the Blessed Dementia Scale, Part 1 and its revised version, the Interview for Deterioration in Daily Living with Dementia, the Unified Activities of Daily Living, and the Dependence Scale. The Progressive Deterioration Scale and Quality of Life Assessment were classified as quality of life scales. The majority of the scales were found to exhibit serious limitations, such as incomplete reliability and validity assessment for the intended uses. The most pervasive problem was a lack of data on responsiveness to change. It is recommended that further research be conducted to develop new tools or enhance existing measures for the assessment of both quality of life and functional ability.

Review of outcome measurement instruments in Alzheimer's disease drug trials: psychometric properties of behavior and mood scales.

This article reviews the reliability and validity of eight scales for behavior and mood problems that were identified in a comparative analysis of Alzheimer's disease (AD) drug trials. The scales are the Brief Psychiatric Rating Scale, the Alzheimer's Disease Assessment Scale-noncognitive, the Relative's Assessment of Global Symptomatology, the Consortium to Establish a Registry for Alzheimer's Disease-Behavior Rating Scale for Dementia, the Dementia Behavior Disturbance scale, the Neuropsychiatric Inventory, and two scales for depressive symptoms, the Cornell Scale for Depression in Dementia and the Dementia Mood Assessment Scale. This article also examines methodological limitations in the way the published literature has assessed the psychometric properties of these scales. The aim is to help clinicians and potential trial investigators select appropriate measurement instruments with which to assess behavior and mood problems in AD and to assist AD researchers in the evaluation of the psychometric properties of such scales.

Review of outcome measurement instruments in Alzheimer's disease drug trials: psychometric properties of global scales.

The use of global outcome measures with strong psychometric properties in Alzheimer's disease (AD) drug trials is encouraged. This article focuses on Clinician Global Impression of Change scales, the Clinical Dementia Rating, and the Global Deterioration Scale to provide (1) a review of psychometric properties, (2) a critique of how these properties are assessed in the literature, and (3) a basis for evaluating, from the standpoint of psychometric properties, the appropriateness of using a given global scale in a drug trial. Reported reliability and validity estimates for the aforementioned scales range from fair to very good, but small sample sizes and/or inappropriate measures of correlation weaken the quality of the evidence. There is also a dearth of published information on responsiveness to change. Researchers planning AD drug trials should consider these issues, along with the interval between test administrations for test-retest reliability, to help select appropriate global outcome measurement instruments.

High-dose progesterone infusion in healthy males: evidence against antiglucocorticoid activity of progesterone.

High concentrations of unbound cortisol in late pregnancy have been explained by the antiglucocorticoid activity of high progesterone levels. To further test this hypothesis we studied the effect of high-dose progesterone on baseline and corticotrophin-releasing hormone (CRH)-induced hormone secretion in humans. In a double-blind crossover study eight healthy male volunteers received either progesterone (0.714 mg.kg-1.h-1 for 60 min followed by a dose of 0.45 mg.kg-1.h-1 over a total infusion time of 315 min) or vehicle as a continuous intravenous infusion. At 210 min a CRH test (0.1 microgram/kg body weight as bolus iv) was performed. Within 30 min after the start of progesterone administration the serum progesterone level increased to 454 +/- 31 nmol/l and remained in the range of third trimester pregnancy concentrations throughout the infusion period. During vehicle infusion the progesterone level remained in the normal range for healthy males and demonstrated a small but significant increase after CRH (1.52 +/- 0.23 vs 0.74 +/- 0.14 mmol/l; p < 0.01). However, baseline and CRH-stimulated serum cortisol and plasma adrenocorticotrophic hormone remained unaffected by high-dose progesterone. Moreover, unbound salivary cortisol also was not affected by progesterone, suggesting that there is no significant competition for transcortin binding sites. In conclusion, no antiglucorticoid activity was found after short-term administration of progesterone in males. These findings cast doubts on the concept that the alterations of the pituitary-adrenal axis in late pregnancy are induced by the antiglucocorticoid activity of high progesterone concentrations.