Weighing the outcomes

The emergent healthcare value era, its consequences, and what drug firms need to do about it.     

Comparing healthcare outcomes.

Governments are increasingly concerned to compare the quality and effectiveness of healthcare interventions but find this a complex matter. Crude hospital statistics can be dangerously misleading and need adjusting for case mix, but identifying and weighting the patient characteristics which affect prognosis are problematical for conceptual, methodological, and practical reasons. These include the inherently uncertain nature of prognosis itself and the practical difficulties of collecting and quantifying data on the outcomes of interest for specific healthcare interventions and known risk factors such as severity.     

Unexpected alpha-stereochemical outcomes of attempted beta-glycosylations

In an effort to prepare complex oligosaccharide derivatives, a series of unexpected alpha glycosides were predominantly formed in the presence of neighboring group participation using imidates or thioglycosides as glycosyl donors under standard glycosylation conditions. The observations are especially suitable in the case of alpha-(1-->3) glycosidic bond formation.     

Determinants and outcomes of mitochondrial dynamics

1. Download : Download high-res image (215KB)
2. Download : Download full-size image

     

Context-dependent outcomes of subarctic grass-endophyte symbiosis

Symbiotic interactions are often context-dependent. We explored how different habitats have modified the symbiosis between the grass Festuca rubra and the endophyte Epichloë festucae. We grew endophytic and endophyte-free grasses originating from subarctic meadows and open river banks in a growth chamber with a hemiparasitic plant (Rhinanthus minor) and a competitor (Achillea millefolium), representing typical plant-plant interactions in meadows. Grasses from meadows were more adapted to plant species interactions than river bank grasses, and the presence of the endophyte strengthened this difference further. Endophyte-infected meadow grasses did not suffer from the hemiparasite, but the endophyte decreased the tolerance of the river bank grasses to the hemiparasite. Endophytic river bank grasses invested more than meadow grasses in vegetative spread. These results suggest differentiation of grass-endophyte symbiota between the habitats, and underline the context dependency of species interactions as well as the role of symbionts in the habitat adaptation of plants.     

On meta-analytic assessment of surrogate outcomes

We discuss the strengths and weaknesses of the meta-analytic approach to estimating the effect of a new treatment on a true clinical outcome measure, T, from the effect of treatment on a surrogate response, S. The meta-analytic approach (see Daniels and Hughes (1997) 16, 1965-1982) uses data from a series of previous studies of interventions similar to the new treatment. The data are used to estimate relationships between summary measures of treatment effects on T and S that can be used to infer the magnitude of the effect of the new treatment on T from its effects on S. We extend the class of models to cover a broad range of applications in which the parameters define features of the marginal distribution of (T, S). We present a new bootstrap procedure to allow for the variability in estimating the distribution that governs the between-study variation. Ignoring this variability can lead to confidence intervals that are much too narrow. The meta-analytic approach relies on quite different data and assumptions than procedures that depend, for example, on the conditional independence, at the individual level, of treatment and T, given S (see Prentice (1989) 8, 431-440). Meta-analytic calculations in this paper can be used to determine whether a new study, based only on S, will yield estimates of the treatment effect on T that are precise enough to be useful. Compared to direct measurement on T, the meta-analytic approach has a number of limitations, including likely serious loss of precision and difficulties in defining the class of previous studies to be used to predict the effects on T for a new intervention.     

Different outcomes of telomere-dependent anaphase bridges

Chromosomal instability occurs early in the development of cancer and may represent an important step in promoting the multiple genetic changes required for the initiation and/or progression of the disease. Telomere erosion is one of the factors that contribute to chromosome instability through end-to-end chromosome fusions entering BFB (breakage-fusion-bridge) cycles. Uncapped chromosomes with short dysfunctional telomeres represent an initiating substrate for both pre- and post-replicative joining, which leads to unstable chromosome rearrangements prone to bridge at mitotic anaphase. Resolution of chromatin bridge intermediates is likely to contribute greatly to the generation of segmental chromosome amplification events, unbalanced chromosome rearrangements and whole chromosome aneuploidy. Accordingly, telomere-driven instability generates highly unstable genomes that could promote cell immortalization and the acquisition of a tumour phenotype.     

Non-medical treatments and their outcomes

This article focuses on outcomes of Spiritualist treatments based upon a series of follow-up studies of patients who came to a Spiritualist temple situated in a rural region of Mexico. Categories of temple patients and conditions under which they resort to alternate therapeutic regimes are also examined. Follow-ups reveal that Spiritualist healers fail more than they succeed in treating their patients. The data suggest that therapeutic benefits from Spiritualist healing tend to occur in four types of disorders — simple diarrheas, simple gynecological disorders, somatized syndromes and minor psychiatric disorders. The findings suggest that successful treatment outcomes are effected not only by concrete manipulation of physiological symptoms but by symbolic manipulation as well. That is, for a therapeutic regime to do its job it must confront cultural imperatives and employ cultural symbols relevant to the removal of the sick role. An unexpected finding of the study reveals that, in the Mexican case, the cultural imperatives relate to cleaning and purification, mediated by tactile communication, which serve symbolically to terminate the sick role.Eastern Michigan UniversityI very gratefully acknowledge the support from the National Science Foundation (Grant # BNS 77 13980) for this research and I am particularly thankful to Vivian Garrison and Arthur Kleinman for their very valuable comments.     

Conditional outcomes in mutualistic interactions

Interspecific interactions are traditionally displayed in a grid in which each interaction is placed according to its outcome (positive, negative or neutral) for each partner. However, recent field studies consistently find the costs and benefits that determine net effects to vary greatly in both space and time, inevitably causing outcomes within most interactions to vary as well. Interactions show 'conditionality' when costs and benefits, and thus outcomes, are affected in predictable ways by current ecological conditions. The full range of natural outcomes of a given association may reveal far more about its ecological and evolutionary dynamics than does the average outcome at a given place and time.     

Non-medical treatments and their outcomes

This article is the second of a two-part discussion of non-medical treatment outcomes based upon follow-ups of patients at a Spiritualist temple situated in a rural region of Mexico. The first part of the analysis focussed on two of three categories of patients seeking treatment there (i.e., habitual temple users and first comers). Unlike these two categories of patients who are not believers in Spiritualism, the present concern is with the category of patients (i.e., regulars) who identify Spiritualism as their religion and believe in Spiritualist ideology. These patients require separate consideration because, unlike the others, they are exposed to several Spiritualist therapeutic modalities which influence treatment outcomes. Follow-ups of these patients reveal the dialectical relationship and the gradual nature of the healing process. Spiritualist treatment outcomes are assessed by an interplay of physiological, psychological, sociological, and cultural paradigms. The hypothesis is advanced that while Spiritualist healers frequently fail to eliminate patients' subjectively perceived symptoms, the therapies to which these patients are subject alter cognition by facilitating pain tolerance and promote response to cultural symbols employed by temple healers. Examination of treatment outcomes of these patients also calls attention to syndromes which fail to respond to Spiritualist therapy including psychotic episodes. A brief comparison is made between Spiritualist treatment outcome and psychotherapy which leads to the conclusion that Spiritualists succeed no less than the latter in eliminating the sick role, restoring the individual's behavioral capacities, and eliminating the feeling of being sick.