A generic model for the assessment of disease epidemiology: the computational basis of DisMod II

Reliable and comparable analysis of risks to health is key for preventing disease and injury. Causal attribution of morbidity and mortality to risk factors has traditionally been conducted in the context of methodological traditions of individual risk factors, often in a limited number of settings, restricting comparability.     

Population health metrics: crucial inputs to the development of evidence for health policy

Valid, reliable and comparable measures of the health states of individuals and of the health status of populations are critical components of the evidence base for health policy. We need to develop population health measurement strategies that coherently address the relationships between epidemiological measures (such as risk exposures, incidence, and mortality rates) and multi-domain measures of population health status, while ensuring validity and cross-population comparability.     

A study of the psychometric properties of the Fagestrom Test for Nicotine Dependence

A factor analysis of 772 Fagestrom Test for Nicotine Dependence (FTND) was performed in a population of French workers with STATISTICA software, utilizing tetrachoric correlations to account for the dichotomous responses of the FTND. Confirmatory factorial analysis found the two-factor solution recently proposed for the FTND to be unsatisfactory. An exploratory factorial analysis concluded that the best solution was monofactorial when Item 3 was deleted. A confirmatory factorial analysis of the FTND provided support for this monofactorial solution. With the deletion of Item 3, the FTND achieved a high internal consistency (Cronbach's alpha=.86). Thus, a revision of the FTND with the exclusion of Item 3 is proposed. This revised form of the FTND appears to assess a unidimensional construct indicating robust construct validity.     

Limitations of current Parkinson's disease therapy

Levodopa and other dopaminergic medications drastically improve the motor symptoms and quality of life of patients with Parkinson's disease in the early stages of the disease. However, once the "honeymoon" period has waned, usually after a few years of dopaminergic therapy, patients become progressively more disabled despite an ever more complex combination of available antiparkinsonian treatments. Sooner or later, they suffer from "dopa-resistant" motor symptoms (speech impairment, abnormal posture, gait and balance problems), "dopa-resistant" nonmotor signs (autonomic dysfunction, mood and cognitive impairment, sleep problems, pain) and/or drug-related side effects (especially psychosis, motor fluctuations, and dyskinesias). Therefore, the current antiparkinsonian therapy cannot be considered as ideal with regard to both efficacy and safety.     

Breast and cervical cancer survival: making sense of ‘league tables’

During 1998, the Department of Health proposed to use survival rates of cervical and breast cancer in the 1989/90 incidence cohort as indicators of care. Valid interpretation was of concern within Trent and the Trent Cancer Registry responded by performing additional analyses. Trent Cancer Registry registrations for 1989/90 were re-analysed and the stability of districts' ranks for that cohort was investigated using random simulation techniques. Stability of ranks across more recent cohorts was investigated and attempts made to use all available information.The Department of Health's analyses were confirmed by our re-analysis of the 1989/90 cohort: Rotherham residents appeared to have the "worst" survival for cervical cancer, and Sheffield residents for breast cancer, although not statistically significantly so. Random simulations indicated that ranks based on a single cohort are not stable: for example Sheffield (ranked tenth for 1-y breast cancer survival) was ranked third or better in 6% of randomisations. Ranks were also unstable across cohorts: for example Rotherham 1-y cervical cancer survival was ranked tenth for 1989/90, fifth for 1991/92 and tenth for 1993/94. Analysis of 3-y running averages provided better information than the league table approach. Most districts improved over time, to different degrees, and similar sized gaps remained between the "best" and the "worst" districts. This analysis illustrates the need to be circumspect when interpreting "league tables" based on a single year or cohort analysis. League tables are based on ranks: clearly a large difference in rank may reflect only trivial (ie medically unimportant) differences in actual outcome. Lack of a statistically significant difference in survival between two districts does not mean their survival is equivalent. Even for a common cancer, like breast cancer, rankings were unstable from cohort to cohort. At the Registry we propose to perform these trend analyses routinely in future, adjusting, when possible, for the effects of deprivation and stage at diagnosis.     

Adverse drug reactions to dopamine agonists: A comparative study in the french pharmacovigilance database

Pharmacodynamical differences between dopamine agonists (DAs) suggest differences in their adverse drug reactions (ADRs) profile. In this study, frequencies of ADR to DAs or levodopa reports in the French Pharmacovigilance Database were explored. Reports occurring between January 1, 1984 and December 31, 2008 were selected (2,189 for DAs and 1,315 for levodopa). The numbers of ADRs by system organ class were compared using ropinirole as a reference. Diurnal somnolence was less frequently reported with all DAs when compared with ropinirole (P < 0.001). Impulse control disorders (ICDs) were more frequently reported with pramipexole (P < 0.001). Significant difference was found among DAs in the frequency of confusion or disorientation (P < 0.001), nausea and vomiting (P < 0.05), or edemas (P < 0.001). No difference among DAs was observed in the frequency of hallucination or arterial hypotension ADR reports (P = 0.3 and P = 0.1). Pleural effusions were more frequently reported with pergolide or bromocriptine (P < 0.001). Somnolence or ICD reports were less frequent with levodopa, whereas confusion was more frequently reported. In summary, our data show significant differences in the kind of ADRs reported for each DA. © 2010 Movement Disorder Society.     

Abnormal surfactant composition and activity in severe bronchiolitis

A prospective study of infants under 1 y of age, ventilated for severe viral bronchiolitis, was carried out in four paediatric intensive care units in order to study surfactant activity and composition in this condition. Lung lavage fluid from 24 infants with bronchiolitis, 19 with bronchiolitis and sepsis or cardiac failure and 12 controls were analysed by the “click test” for surfactant activity and for phospholipids. Surfactant activity was present in all controls, but in only 2 of the 24 infants with bronchiolitis alone. The presence of phosphatidylglycerol correlated perfectly with the click test, suggesting that reduced activity is due to changes in surfactant lipid composition. In those with bronchiolitis plus coexisting disease, surfactant activity and phosphatidylglycerol were absent in only half. Surfactant activity and phosphatidylglycerol re-appeared by extubation. Severe viral bronchiolitis is associated with an absence of surfactant activity and PG, which resolves by clinical recovery. Infants with coexisting conditions are not always surfactant deficient. Surfactant administration is likely to be beneficial, but requires a selective approach.