Explore the vast range of titles available.

In diverse fields of empirical research—including many in the biological sciences—attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from \"single mediator theory\" to \"multiple mediator practice,\" highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed.

Summary Background Epidemiological surveillance of Creutzfeldt-Jakob disease (CJD) was reinstituted in the UK in 1990 to identify any changes in the occurrence of this disease after the epidemic of bovine spongiform encephalopathy (BSE) in cattle. Methods Case ascertainment of CJD was mostly by direct referral from neurologists and neuropathologists. Death certificates on which CJD was mentioned were also obtained. Clinical details were obtained for all referred cases, and information on potential risk factors for CJD was obtained by a standard questionnaire administered to patients' relatives. Neuropathological examination was carried out on approximately 70% of suspect cases. Epidemiological studies of CJD using similar methodology to the UK study have been carried out in France, Germany, Italy, and the Netherlands between 1993 and 1995. Findings Ten cases of CJD have been identified in the UK in recent months with a new neuropathological profile. Other consistent features that are unusual include the young age of the cases, clinical findings, and the absence of the electroencephalogram features typical for CJD. Similar cases have not been identified in other countries in the European surveillance system. Interpretation These cases appear to represent a new variant of CJD, which may be unique to the UK. This raises the possibility that they are causally linked to BSE. Although this may be the most plausible explanation for this cluster of cases, a link with BSE cannot be confirmed on the basis of this evidence alone. It is essential to obtain further information on the current and past clinical and neuropathological profiles of CJD in the UK and elsewhere.

To determine the impact of insecticide-treated curtains (ITC) on all-cause child mortality (6-59 months) over a period of six years. To determine whether initial reductions in child mortality following the implementation of ITC are sustained over the longer term or whether \"delayed\" mortality occurs. A rural population of ca 100 000 living in an area with high, seasonal Plasmodium falciparum transmission was studied in Burkina Faso. Annual censuses were conducted from 1993 to 2000 to measure child mortality. ITC to cover doors, windows, and eaves were provided to half the population in 1994 with the remainder receiving ITC in 1996. Curtains were re-treated or, if necessary, replaced annually. Over six years of implementation of ITC, no evidence of the shift in child mortality from younger to older children was observed. Estimates of the reduction in child mortality associated with ITC ranged from 19% to 24%. In our population there was no evidence to suggest that initial reduction in child mortality associated with the introduction of insecticide-treated materials was subsequently compromised by a shift in child mortality to older-aged children. Estimates of the impact of ITC on child mortality in this population range from 19% to 24%.

Purpose To document public awareness and knowledge of glaucoma. Patients and methods The study used health knowledge questionnaires. (a) A short, structured telephone interview was performed with a nationally representative sample of 1009 people. (b) A more detailed questionnaire was administered in two contrasting regions by telephone (500 interviews from the Isle of Wight and 226 interviews from Ealing) or face to face (300 interviews from Ealing). Results Between 71 and 93% of those interviewed by telephone reported having heard of glaucoma, compared with only 23% of those interviewed face to face in Ealing. Of those who reported having heard of glaucoma, over 80% had at least some knowledge about the disease. Conclusion This is the first study of public awareness of glaucoma across the UK. We found a relatively high level of awareness and knowledge of glaucoma in the general UK population, but identified at least one pocket of poor knowledge in a specific sub-population.

Several million children are killed each year by diarrhoeal diseases; preventive strategies appropriate for developing countries are vital. Despite strong circumstantial evidence that flies are vectors of diarrhoeal diseases, no convincing studies of the impact of fly control on diarrhoea incidence in developing countries have been reported. We undertook a randomised study of the effect of insecticide spraying on diarrhoea incidence. Six study villages were randomly assigned to two groups. Flies were controlled through insecticide application in group A in 1995 and in group B in 1996. In 1997 the effectiveness of baited fly traps was tested in group A villages. Diarrhoea episodes were monitored in children under 5 years through mothers' reports during weekly visits by a health visitor. Fly density was monitored by use of sticky fly-papers hung in sentinel compounds. During the fly seasons (March–June) of both 1995 and 1996, insecticide application practically eliminated the fly population in the treated villages. The incidence of diarrhoea was lower in the sprayed villages than in the unsprayed villages in both 1995 (mean episodes per child-year 6·3 vs 7·1) and 1996 (4·4 vs 6·5); the reduction in incidence was 23% (95% CI 11–33, p=0·007). At times other than the fly season there was no evidence of a difference in diarrhoea morbidity between sprayed and unsprayed villages. Fly density data for 1997 indicate the ineffectiveness of baited traps in this setting. Fly control can have an impact on diarrhoea incidence similar to, or greater than, that of the interventions currently recommended by WHO for inclusion in diarrhoeal disease control programmes in developing countries. This important finding needs confirmation in other settings in developing countries. Technologies and practices that interrupt disease transmission by flies need to be developed and promoted.

In 2002, 17 people died from variant CJD (vCJD) in the UK, compared with 20 in 2001 and 28 in 2000. We analysed data for deaths from vCJD since 1995 and estimated the underlying trend in mortality. The trend had a quadratic component (p=0·005), suggesting that the increase was not exponential, and that the previously increasing trend is slowing down. The death rate peaked in 2000. These findings are encouraging, but mortality might increase again in the future.

Back-calculation analysis of the variant Creutzfeldt-Jakob disease epidemic in the United Kingdom is used to estimate the number of infected individuals and future disease incidence. The model assumes a hazard of infection proportional to the incidence of bovine spongiform encephalopathy in the United Kingdom and accounts for precautionary control measures and very wide ranges of incubation periods. The model indicates that current case data are compatible with numbers of infections ranging from a few hundred to several millions. In the latter case, the model suggests that the mean incubation period must be well beyond the human life-span, resulting in disease epidemics of at most several thousand cases.

The number of deaths from variant CJD (vCJD) in the UK increased in the last quarter of 1998, although numbers were lower in subsequent quarters. We analysed the numbers of definite and probable (living and dead) vCJD cases since 1994 to assess trends in incidence. We estimated that the number of onsets increased by 23% per year for 1994–2000 (p=0·004), and that deaths increased by 33% for 1995–2000 (p=0·005). The absolute number of cases in the UK is still low, but such an increase should be a matter of concern.

Fourteen cases of new-variant Creutzfeldt–Jakob disease have so far been confirmed in the United Kingdom. Are they the start of an epidemic? If so, how informative will cases in the next few years be in predicting its course?

The unusually high number of deaths from varian Creutzfeldt-Jakob disease occurring in the last quarter of 1998 should be intepreted with caution.