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Health professionals, their medical interventions and uncertainty: a study focusing on women at midlife.

Health professionals face a tension between focusing on the individual and attending to health issues for the population as a whole. This tension is intrinsic to medicine and gives rise to medical uncertainty, which here is explored through accounts of three medical interventions focused on women at midlife: breast screening, hormone replacement therapy and bone densitometry. The accounts come from interviews with UK health professionals using these medical interventions in their daily work. Drawing on the analysis of Fox [(2002). Health and Healing: The public/private divide (pp. 236-253). London: Routledge] we distinguish three aspects of medical uncertainty and explore each one of them in relation to one of the interventions. First is uncertainty about the balance between the individual and distributive ethic of medicine, explored in relation to breast screening. Second is the dilemma faced by health professionals when using medical evidence generated through studies of populations and applying this to individuals. We explore this dilemma for hormone replacement therapy. Thirdly there is uncertainty because of the lack of a conceptual framework for understanding how new micro knowledge, such as human genetic information, can be combined with knowledge of other biological and social dimensions of health. The accounts from the bone denistometry clinic indicate the beginnings of an understanding of the need for such a framework, which would acknowledge complexity, recognising that factors from many different levels of analysis, from heredity through to social factors, interact with each other and influence the individual and their health. However, our analysis suggests biomedicine continues to be dominated by an individualised, context free, concept of health and health risk with individuals alone responsible for their own health and for the health of the population. This may continue to dominate how we perceive responsibilities for health until we establish a conceptual framework that recognises the complex interaction of many factors at macro and micro level affecting health.

Absorptiometry, Photon↗

Optimizing a portfolio of health care programs in the presence of uncertainty and constrained resources.

Much research has been devoted to handling uncertainty in cost-effectiveness analysis. The current literature suggests summarizing uncertainty in cost-effectiveness analysis using acceptability curves or net health benefits. These approaches, however, focus only on uncertainty associated with costs and effects of the programs under consideration. In the real world, most decision-makers have to fund a portfolio of health care programs. Therefore, a more comprehensive approach would include in the analysis the uncertainty of costs and effects of all programs supported by the fixed budget. This paper extends the decision rule described by Birch and Gafni (J. Health Econ. 11(3) (1992) 279) within the context of a portfolio of programs when costs and effects are uncertain and resources constrained.

Budgets↗

The impact of contouring uncertainty on rectal 3D dose-volume data: results of a dummy run in a multicenter trial (AIROPROS01-02).

PURPOSE: To estimate the impact of the uncertainty in contouring the rectum on rectal dose-volume parameters and normal tissue complication probability (NTCP) in a prospective (AIROPROS01-02) investigation about rectal toxicity. METHODS AND MATERIALS: The participants in a prospective trial (18 observers) were asked to draw the external contour of the rectum of 4 sample patients (3 patients undergoing radical conformal radiotherapy, 1 patient undergoing post-prostatectomy) on CT images (0.5 cm spacing) using a 3D treatment planning system. A previously accepted definition of cranial and caudal borders of the rectum was applied. For each patient, four- and six-field 3D-conformal techniques (70-76 Gy, ICRU dose) were planned and DVH/dose statistics of the rectum were calculated. The impact of interobserver variability on rectal volume, cranial and caudal borders, mean, maximum, and median rectal dose, percentage of rectum receiving more than 40, 45, 50, 55, 60, 65, 70, and 75 Gy (V(40)-V(75)), and NTCP were investigated. RESULTS: Concerning DVHs, 9/18 observers tended to have some systematic deviation. However, deviations from the mean values greater than 5% were found only in 1/9 because of a systematic discrepancy in the caudal limit assessment (mean deviation from the most frequently chosen slice: 8 mm). No other observers showed a mean deviation in the cranial or the caudal limit definition greater than 5.8 mm. For another observer, it was possible to clearly assess the cause of a relatively large systematic deviation for DVH parameters. In both cases, the observers were contacted to avoid these systematic deviations. When considering the remaining 16/18 observers, the average values of SD for V(40)-V(75) ranged between 1% and 4% and were found to be lower (<3%) for the 3 nonoperated patients. The average values of the SD were around 1.5-2 Gy and less than 1.5% for mean/median dose and NTCPs, respectively. CONCLUSIONS: Concerning the uncertainty in rectum definition, the collection of rectal dose-volume data in multicenter investigations seems to be feasible after a clear and previously accepted definition of rectum is assessed. However, even with a general agreement on rectum definition, contouring appears to be a quite significant source of uncertainty. A dummy run procedure is useful in identifying possible discrepancies among single observers and in assessing reliable confidence levels on dose-volume constraints because of contouring uncertainty, making the dummy run mandatory in multicenter trials evaluating 3D dose-volume data.

Humans↗

Application of uncertainty analysis in assessing dietary exposure.

Conventional approaches for assessing dietary exposure to contaminants and additives in food are deterministic, using point estimates for consumption and contamination. In reality, both consumption and contamination are variable. Furthermore our knowledge of them is uncertain, e.g. due to measurement uncertainty. Conventional approaches attempt to allow for this by using worst-case assumptions or safety factors, but these are often subjective and may result either in overestimation or underestimation of the true range of exposures. Probabilistic approaches take account of variability and uncertainty by using distributions rather than point estimates for consumption and contamination. The outputs are distributions for exposure, which provide a more complete and balanced description of risk for the decision-maker. These approaches also facilitate the use of sensitivity analysis to identify those factors that impact most on exposure, and to identify areas of uncertainty where additional data will improve exposure estimates. This paper reviews examples of the application of these methods to the assessment of dietary exposure to food contaminants, including dioxins in seafood, where it was found that the greatest uncertainties relate to toxicity rather than exposure. Further work required to implement probabilistic approaches for dietary exposure assessment is discussed.

Dioxins↗

Life situation related to the ICD implantation; self-reported uncertainty and satisfaction in Swedish and US samples.

The aim of the study was to describe changes in the life situation related to the ICD implantation of Swedish and US samples with regard to uncertainty and satisfaction. The life situation was measured by reference to the uncertainty caused by the condition and satisfaction with the life situation. Inferential statistics were used to analyse changes within and between the Swedish and US samples. Uncertainty showed a statistically significant difference between the Swedish and US samples before as well as after the ICD implantation. A higher level of uncertainty was indicated for the US sample prior to the ICD implantation and for the Swedish sample following the implantation. In the Swedish sample, satisfaction with life showed a statistically significant difference within the socio-economic domain, indicating a higher degree of satisfaction 3 months after implantation. Satisfaction within the domains of health and functioning, socio-economics and psychological-spiritual showed a statistically significant difference between the Swedish and US samples both before and after ICD implantation, indicating a higher degree of satisfaction in the US sample. The previous study shows that the ICD-patient's life situation is changed after the implantation and that it is necessary to provide the patient with information and education based on their own preconditions. The fact that US sample was investigated at a later stage after ICD implantation than the Swedish sample may have influenced the results of the study.

Aged↗

Impact of uncertainty on cost-effectiveness analysis of medical strategies: the case of high-dose chemotherapy for breast cancer patients.

OBJECTIVES: The object of this study was to determine, taking into account uncertainty on cost and outcome parameters, the cost-effectiveness of high-dose chemotherapy (HDC) compared with conventional chemotherapy for advanced breast cancer patients. METHODS: An analysis was conducted for 300 patients included in a randomized clinical trial designed to evaluate the benefits, in terms of disease-free survival and overall survival, of adding a single course of HDC to a four-cycle conventional-dose chemotherapy for breast cancer patients with axillary lymph node invasion. Costs were estimated from a detailed observation of physical quantities consumed, and the Kaplan-Meier method was used to evaluate mean survival times. Incremental cost-effectiveness ratios were evaluated successively considering disease-free survival and overall survival outcomes. Handling of uncertainty consisted in construction of confidence intervals for these ratios, using the truncated Fieller method. RESULTS: The cost per disease-free life year gained was evaluated at 13,074 Euros, a value that seems to be acceptable to society. However, handling uncertainty shows that the upper bound of the confidence interval is around 38,000 Euros, which is nearly three times higher. Moreover, as no difference was demonstrated in overall survival between treatments, cost-effectiveness analysis, that is a cost minimization, indicated that the intensive treatment is a dominated strategy involving an extra cost of 7,400 Euros, for no added benefit. CONCLUSIONS: Adding a single course of HDC led to a clinical benefit in terms of disease-free survival for an additional cost that seems to be acceptable, considering the point estimate of the ratio. However, handling uncertainty indicates a maximum ratio for which conclusions have to be discussed.

Adolescent↗

A review of the scientific basis for uncertainty factors for use in quantitative risk assessment for the induction of allergic contact dermatitis.

Safety evaluations for chemicals which possess the ability to cause sensitization by skin contact have traditionally been done using an ad hoc comparative risk assessment technique. Recently, several papers have been published supporting the use of an alternative, and potentially better, quantitative risk assessment approach. While they represent a relatively new approach to risk assessment for sensitizers, quantitative methods have been used for decades to support risk assessments for systemic toxicity. Historically, these methods have involved the extrapolation of toxicity data - generally from studies in laboratory animals at relatively high doses to human exposures at lower doses. For toxicity endpoints with a threshold, this process has traditionally involved the use of uncertainty factors. For example, uncertainty factors are commonly used to extrapolate from laboratory animals to humans, and from 'average' humans to sensitive subpopulations. In the absence of data to support a different value, a default factor of 10 is widely accepted for each of these areas. Recent papers have advocated the use of a similar approach to characterize the risk of the induction of skin sensitization by allergens of varying potency and potential for skin contact. As with other forms of toxicity, a quantitative assessment of risk for allergic skin reactions can be approached by identifying a NOAEL (no observed adverse effect level) and applying appropriate uncertainty factors. Three major areas of data extrapolation have been identified: inter-individual susceptibility, the influence of vehicle or product matrix, and exposure considerations. This paper provides an overview of each of these areas with an evaluation of the available scientific database to support an uncertainty factor in the range of 1-10 for each area.

Data Interpretation, Statistical↗

Rhesus macaques (Macaca mulatta) monitor uncertainty during numerosity judgments.

Two rhesus macaques (Macaca mulatta) judged arrays of dots on a computer screen as having more or fewer dots than a center value that was never presented in trials. After learning a center value, monkeys were given an uncertainty response that let them decline to make the numerosity judgment on that trial. Across center values (3-7), errors occurred most often for sets adjacent in numerosity to the center value. The monkeys also used the uncertainty response most frequently on these difficult trials. A 2nd experiment showed that monkeys' responses reflected numerical magnitude and not the surface-area illumination of the displays. This research shows that monkeys' uncertainty-monitoring capacity extends to the domain of numerical cognition. It also shows monkeys' use of the purest uncertainty response possible, uncontaminated by any secondary motivator.

Animals↗

The role of illness uncertainty on coping with fibromyalgia symptoms.

This study examined the role of illness uncertainty in pain coping among women with fibromyalgia (FM), a chronic pain condition of unknown origin. Fifty-one FM participants completed initial demographic and illness uncertainty questionnaires and underwent 10-12 weekly interviews regarding pain, coping difficulty, and coping efficacy. Main outcome measures included weekly levels of difficulty coping with FM symptoms and coping efficacy. Multilevel analyses indicated that pain elevations for those high in illness uncertainty predicted increases in coping difficulty. Furthermore, when participants had more difficulty coping, they reported lower levels of coping efficacy. Results were consistent with hypothesized effects. Illness uncertainty accompanied by episodic pain negatively influenced coping efficacy, an important resource in adaptation to FM.

Adaptation, Psychological↗

Schizophrenia subjects show intact success-related neural activation but impaired uncertainty processing during decision-making.

Decision-making is a complex process that is important for everyday life. This study examined the effect of the degree of success, and outcome uncertainty, on decision-making and associated neural substrate activation in schizophrenia subjects (SZS) and normal comparison subjects (NCS). A total of 15 subjects with a diagnosis of schizophrenia and 15 age- and education-matched NCS participated in this study. These subjects completed the two-choice prediction task during functional magnetic resonance imaging. Decision-making characteristics and activation of neural substrates were obtained at 20, 50, or 80% error rate. Success and uncertainty influenced the behavioral characteristics on the two-choice prediction task, and the task-related activation in SZS and NCS. Neither success nor uncertainty differentially affected the behavioral characteristics of SZS relative to NCS during the two-choice prediction task. Nonetheless, there was a significant interaction between group and error rate in bilateral parietal cortex. The activation in NCS was the highest when the outcome was most uncertain. In contrast, task-related activation in SZS was not modulated by the degree of uncertainty. Thus, SZS failed to utilize the parietal cortex to process decision-making situations with highly uncertain outcomes.

Adult↗

Optimising uncertainty in physical sample preparation.

Uncertainty associated with the result of a measurement can be dominated by the physical sample preparation stage of the measurement process. In view of this, the Optimised Uncertainty (OU) methodology has been further developed to allow the optimisation of the uncertainty from this source, in addition to that from the primary sampling and the subsequent chemical analysis. This new methodology for the optimisation of physical sample preparation uncertainty (u(prep), estimated as s(prep)) is applied for the first time, to a case study of myclobutanil in retail strawberries. An increase in expenditure (+7865%) on the preparatory process was advised in order to reduce the s(prep) by the 69% recommended. This reduction is desirable given the predicted overall saving, under optimised conditions, of 33,000 pounds Sterling per batch. This new methodology has been shown to provide guidance on the appropriate distribution of resources between the three principle stages of a measurement process, including physical sample preparation.

Data Interpretation, Statistical↗

Uncertainty in the age of fossils and the stratigraphic fit to phylogenies.

The ages of first appearance of fossil taxa in the stratigraphic record are inherently associated to an interval of error or uncertainty, rather than being precise point estimates. Contrasting this temporal information with topologies of phylogenetic relationships is relevant to many aspects of evolutionary studies. Several indices have been proposed to compare the ages of first appearance of fossil taxa and phylogenies. For computing most of these indices, the ages of first appearance of fossil taxa are currently used as point estimates, ignoring their associated errors or uncertainties. The effect of age uncertainty on measures of stratigraphic fit to phylogenies is explored here for two indices based on the extension of ghost lineages (MSM* and GER). A solution based on randomization of the ages of terminal taxa is implemented, resulting in a range of possible values for measures of stratigraphic fit to phylogenies, rather than in a precise but arbitrary stratigraphic fit value. Sample cases show that ignoring the age uncertainty of fossil taxa can produce misleading results when comparing the stratigraphic fit of competing phylogenetic hypotheses. Empirical test cases of alternative phylogenies of two dinosaur groups are analyzed through the randomization procedure proposed here.

Animals↗

Uncertainties in alanine/ESR dosimetry at the Physikalisch-Technische Bundesanstalt.

In radiation therapy, the effect of ionizing radiation is quantified in terms of the absorbed dose to water. Dosimetry with alanine and readout via electron spin resonance (ESR) is a method which is used as a secondary standard by several national metrology institutions. The advantages of the method are the good water-equivalence of the probes, their small size and the very weak dependence of the response on the radiation quality for MV x-rays and high-energy electrons used in radiation therapy. For radiation therapy, a small uncertainty of the applied dose is required. The present publication describes the determination of the uncertainty budget for the alanine/ESR dosimetry system of the Physikalisch-Technische Bundesanstalt (PTB), which relies on the use of a reference sample. A method is also presented which allows a reduction of the influence of fading or other changes of the ESR amplitude of irradiated alanine probes with time. If certain conditions are met which are described in detail, a relative uncertainty of less than 0.5% can be reached for probes irradiated with (60)Co in the 5-25 Gy dose range, including the uncertainty of the primary standard. First results for dose values between 2 Gy and 10 Gy are presented as well. From the high accuracy achievable with alanine dosimetry, we conclude that this method has great potential to solve measurement problems for modern methods of radiation therapy such as intensity modulated radiation therapy (IMRT) or tomotherapy.

Alanine↗

Propagating uncertainty in microarray data analysis.

Microarray technology is associated with many sources of experimental uncertainty. In this review we discuss a number of approaches for dealing with this uncertainty in the processing of data from microarray experiments. We focus here on the analysis of high-density oligonucleotide arrays, such as the popular Affymetrix GeneChip array, which contain multiple probes for each target. This set of probes can be used to determine an estimate for the target concentration and can also be used to determine the experimental uncertainty associated with this measurement. This measurement uncertainty can then be propagated through the downstream analysis using probabilistic methods. We give examples showing how these credibility intervals can be used to help identify differential expression, to combine information from replicated experiments and to improve the performance of principal component analysis.

Computational Biology↗

Ethical decision making: pressure and uncertainty as complicating factors.

This qualitative study examines social workers' ethical tension as they evaluate decisional capacity of elderly individuals experiencing some degree of cognitive impairment. An interview guide of open-ended questions was used with a convenience sample of 17 home health care social workers. Constant comparative analysis was used to examine factors contributing to ethical tension. Three areas emerged as highly relevant to participants ethical decisions: (1) clinical uncertainty, (2) pressure from other professionals, and (3) a combination of pressure from other professionals and clinical uncertainty. Clinical uncertainty was influenced by partial cognitive impairment, mental health problems, the interplay of health and mental health, and unclear etiology of poor decisional capacity. Pressure from other professionals typically involved issues of compliance and medical safety. Ethical tension was particularly strong when participants experienced both pressure from other professionals and clinical uncertainty.

Adult↗

Bayesian approach for quantifying the uncertainty of neutron doses derived from spectrometric measurements.

Bayesian methods provide a unified framework for combining information in the presence of uncertainty. All uncertainties that enter into the description of a measurement are modelled using probability distributions, and these are handled according to the rules of probability theory, ensuring that the approach is free of inconsistencies. The final result of the analysis is the full probability distribution for the parameter of interest, and from this distribution an appropriate uncertainty interval can be obtained. Some of the advantages of a Bayesian analysis include a straightforward approach to the problem of dealing with nuisance parameters, the ability to incorporate prior information in a natural way and the flexibility that is necessary for a realistic modelling of the measurement process. As an example, the problem of deriving neutron dose estimates and their uncertainties based on measurements carried out using a Bonner sphere spectrometer is considered.

Bayes Theorem↗

Uncertainty intervention for watchful waiting in prostate cancer.

Watchful waiting is a reasonable alternative to treatment for some older men with localized prostate cancer, but it inevitably brings uncertainty. This study tested the effectiveness of the watchful waiting intervention (WWI) in helping men cognitively reframe and manage the uncertainty of watchful waiting. Based on Mishel's Reconceptualized Uncertainty in Illness Theory (Image. 1990; 256-262), the WWI was tested with a convenience sample of 41 men. Experimental subjects received 5 weekly intervention calls from a nurse. Control subjects received usual care. Outcomes were new view of life, mood state, quality of life, and cognitive reframing. Repeated measures of analysis of variance were used to test the effectiveness of the WWI. The sample was 86% Caucasian and 14% African American, with an average age of 75.4 years. Intervention subjects were significantly more likely than controls to view their lives in a new light (P = .02) and experience a decrease in confusion (P = .04) following the intervention. Additionally, intervention subjects reported greater improvement in their quality of life than did controls (P = .01) and believed their quality of life in the future would be better than did controls (P = .01). This study's findings document the benefits of the WWI for patients living with uncertainty.

Adaptation, Psychological↗

Role of continuing supportive cares in increasing social support and reducing perceived uncertainty among women with newly diagnosed breast cancer in Taiwan.

The purpose of this study was to explore the roles of continuing supportive care in increasing the social support and reducing the perceived uncertainty among women newly diagnosed with breast cancer in Taiwan. A longitudinal, quasi-experimental design was used in this study. Sixty-one women younger than 60 years, newly diagnosed with breast cancer and undergoing surgery, were recruited from 2 urban teaching hospitals in northern Taiwan. The experimental group was provided with additional continuing supportive care for 3 months. Two instruments, including the Social Support Questionnaire and an uncertainty questionnaire, were administered to participants at 3 time points: presurgery within 2 weeks after diagnosis, 1 month after surgery, and 3 months after diagnosis. The experimental group reported significantly higher social support and lower disease uncertainty compared with the control group at 1 month after surgery and 3 months after diagnosis. With knowledge of the role that continuing-care intervention plays in social support and disease uncertainty, nurses and other healthcare professionals can continue to explore and strengthen strategies to enhance the coping ability of women with breast cancer in Taiwan.

Adaptation, Psychological↗