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Finding the "natural" vector bases for multidimensional reference values.

The concept of reference values can be extended to multidimensional results. A probability function describes the relative density of the observations in the multivariate space. When the density of a given point is measured relative to all other points, we get an estimate of the density rank of a given point. If the rank of a point is lower than 95 per cent of all points, the multidimensional result is outside the multidimensional reference range. The single-dimensional case is a special case of this general concept. Many observations are needed to define multidimensional distributions. However, less points are needed if the dimensionality of the data matrix is reduced by statistical methods such as principal component analysis (PCA). Also other vector bases than the orthogonal solution produced by PCA are possible, and all of them compress data equally well. So the choice must be based on other criteria than compression. We propose using a vector basis that consists of positive numbers. The positive vectors can be found by direct methods such as Alternating Regression (AR) or they can be modified from the results of the PCA. Positive vectors resemble the spectra that are familiar in chemistry and physics. They are a "natural" way to describe multidimensional results. It is easier to name the positive vectors than the purely statistical vectors of PCA. To obtain a unique positive solution, additional constraints besides positivity are needed.

Clinical Laboratory Techniques↗

Methodological triangulation showed the poorest quality of life in the youngest people following treatment of coronary artery disease: a longitudinal study.

The purpose of the longitudinal study was to describe, explain and understand the subjective health related quality of life (HRQoL) and life course of people (N=280) with coronary artery disease (CAD) during the period following the onset of the disease, the process of therapy and the period of rehabilitation. Methodological triangulation was used in this research. The significance of the results obtained with quantitative and qualitative methods was evaluated by means of meta-analysis. A longitudinal quantitative study was undertaken through the year after the treatments (medication, balloon angioplasty or bypass surgery), and 19 persons attended thematic interviews 1 year after the treatments carried out in their homes. The results of quantitative analysis showed that the male and female CAD patients in the youngest age group had the poorest HRQoL. Although, the patients average HRQoL improved on the dimensions of pain, energy and mobility, it deteriorated on the dimensions of social isolation, sleep and emotional reactions. From the viewpoint of methodological triangulation, the most significant finding was that the qualitative approach provided an explanation for the poor psychosocial HRQoL obtained by the quantitative approach, showing the crucial factor to be age and age-related aspects of the life situation. Interviews and the method of phenomenological psychology helped to gain insight into the informants' situational experience of HROoL and life course, which was not detectable with a questionnaire.

Activities of Daily Living↗

Expression profiling and prediction of distant metastases in head and neck squamous cell carcinoma.

BACKGROUND: For breast and prostate cancer, a gene expression signature of the tumour is associated with the development of distant metastases. Regarding head and neck squamous cell carcinoma (HNSCC), the only known risk factor is the presence of > or =3 tumour-positive lymph nodes. AIM: To evaluate whether a HNSCC gene expression signature can discriminate between the patients with and without distant metastases. METHODS: Patients with HNSCC with and without distant metastases had >3 tumour-positive lymph nodes, and did not differ with respect to other risk factors. Statistical analysis was carried out using Student's t test, as well as statistical analysis of microarrays (SAM), to assess the false discovery rate for each gene. These analyses were supplemented with a newly developed method that computed deviations from gaussian-order statistics (DEGOS). To validate the platform, normal mucosa of the head and neck was included as control. RESULTS: 2963 genes were differently expressed between HNSCC and normal mucosa (t test; p<0.01). More rigorous statistical analysis with SAM confirmed the differential expression of most genes. The comparison of genes in HNSCC with and without metastases showed 150 differently expressed genes (t test; p<0.01), none of which, however, could be confirmed using SAM or DEGOS. CONCLUSIONS: No evidence for a metastasis signature is found, and gene expression profiling of HNSCC has seemingly no value in determining the risk of developing distant metastases. The absence of such a signature can be understood when it is realised that, for HNSCC in contrast with breast cancer, the lymph nodes are a necessary in-between station for haematogenous spread.

Adult↗

Minority youth in foster care: managed care and access to mental health treatment.

BACKGROUND: Public sector mental health treatment has been transformed in recent years by the advent of managed care, but investigators of managed care policy have not yet focused on ethnic minority children, especially those involved with the child welfare system. Because of an overrepresentation of high-need minority children, foster care in particular is important to consider. OBJECTIVES: The present study examined children placed in foster care and documented differences between minority children and youth (black persons, Hispanic persons, and white persons) in use of mental health services. The primary concern of the study was to consider whether there were differences in access to services or service use among the groups in the transition to capitated managed care. MATERIALS AND METHODS: Medicaid claims and encounter data for two experimental managed care sites and one comparison fee-for-service site are used in a "difference-in-difference" analysis to estimate a changes in inpatient, outpatient, and residential treatment center (RTC) utilization, controlling for patient characteristics. RESULTS: The study finds persistent declines in inpatient and outpatient use for all ethnic groups, persistent under-representation of Hispanic persons and black persons in treatment regardless of managed care, and greater use of RTCs by black persons and Hispanic persons that is attributable in part to managed care. CONCLUSIONS: Black and Hispanic children received more rather than less mental health care under capitated managed care. The significance of this shift, largely increased in use of RTCs, however, cannot be determined at present, as the effectiveness of treatment delivered in RTCs is not known.

Adolescent↗

Statistical distribution of factors and factor images in factor analysis of medical image sequences.

From a time or energy image sequence, factor analysis of medical image sequences (FAMIS) estimates factors, representing kinetics or spectra in a given physiological compartment, and associated factor images, showing the compartments corresponding to each curve. In this paper, we show that the statistical properties of factor images and associated factors can be determined using a well known result from elementary probability theory. Numerical experiments are conducted to demonstrate that the variance observed in factor images can be predicted when the statistical properties of the original data are known. It is shown how these theoretical results can be used to relax the non-negativity constraints during FAMIS oblique analysis and to improve the quantitative interpretation of the factor images by associating a confidence interval with each pixel value.

Biophysical Phenomena↗

[Classification of pharmaceutical services from the viewpoint of patient satisfaction/dissatisfaction].

A survey was conducted to examine what the public expects of pharmacists. We created 26 questions based on 26 different situations that patients encounter at pharmacies in order to assess patient satisfaction/dissatisfaction. Some questions were designed to compare pairs of symmetrical situations. The survey was carried out in February and March 2001. The surveys were conducted with patients and/or patients' relatives who brought their prescriptions to pharmacies and with employees of pharmaceutical companies and their family members. A factor analysis extracted two factors among the 26 variables, the first being patient dissatisfaction and the second being patient satisfaction. However, factor loadings for some paired situations were not necessarily symmetrical and thus the absolute values of the scores were not equal. The results suggest that satisfaction on one side does not entail dissatisfaction on the other side and thus satisfaction and dissatisfaction can be examined as separate and distinct entities. Based on these results, we classified pharmaceutical services into two types. The first type is referred to as instrumental service. In this situation patients do not feel great satisfaction even if such service is provided. However, they feel great dissatisfaction if the service is not provided. The second type is referred to as expressive service. These patients feel some satisfaction if such service is provided, however, they do not feel a fatal dissatisfaction if the service is not provided. Our research documents that when examining data based on the assumption that there is a different dimensionality for patient satisfaction and dissatisfaction, it is possible to gain insights into new aspects of pharmaceutical services that are otherwise impossible to assess.

Adolescent↗

Psychometric analysis of the University of Wisconsin Interstitial Cystitis Scale: implications for use in randomized clinical trials.

PURPOSE: A psychometric analysis of the University of Wisconsin Interstitial Cystitis Scale was conducted on 30 females previously enrolled in a phase II double-blind randomized controlled trial evaluating the efficacy of six weekly intravesical instillations of TICE BCG. The analyses were to: (1) evaluate the adequacy of the seven individual IC component items for measuring the range of patient responses; (2) verify the 2-factor (IC versus reference) construct of the scale; (3) evaluate the internal consistency and reliability of the IC items; (4) better define the scale's applicability and limitations; and (5) if possible, make recommendations for improvements in the scale. MATERIALS AND METHODS: Standard psychometric analyses were used to perform the evaluation, and included descriptive analysis of individual items, computing of item-total correlations and Cronbach's internal consistency measures, and the application of factor and Rasch analyses. RESULTS: The original 7-item IC scale was found to have ceiling effects that could limit its use in detecting small therapeutic differences. It was also found that the Pelvic item originally assigned to the reference set of items of the scale should be included as an IC item when used in a comparable IC population. After including this item into the IC scale Cronbach's alpha was 0.84, compared with 0.82. CONCLUSIONS: The UW-IC Scale has psychometric properties similar to other measurement instruments used in clinical research, and appears worthy of further study in well-characterized IC populations. The reference items suggest that IC patients do not indiscriminately report high values for generalized body complaints, but do so on bladder related symptoms as recorded by the IC items of the scale. Although the scale has limitations it appears applicable for use in future IC intervention clinical trials.

Administration, Intravesical↗

Predictive parameters in biologic assessment of low-stage retroperitoneal lymph-node dissection.

In all, 30% of patients felt to have clinical stage A nonseminomatous testis cancer in fact have pathologic stage B disease. Although patients with clinical stage A nonseminoma currently enjoy a very high change for cure, a better assignment of therapy at diagnosis could lead to an overall decrease in the morbidity of treatment. This study analyzed orchiectomy specimens from 102 patients with clinical stage A nonseminomatous testis cancer, all of whom underwent pathologic staging via retroperitoneal lymph-node dissection (RPLND). Various parameters of the orchiectomy specimen were analyzed to determine whether or not clinical staging could be improved on the basis of these factors. Statistical analysis resulted in the following model. If the orchiectomy specimen consisted of 100% embryonal carcinoma the patient was classified as being at high risk for retroperitoneal metastasis. In the absence of this finding the aneuploid cell line as determined by flow cytometry was considered. If the percentage of aneuploid cells in the S phase was less than 29% the patient was felt to be at low risk for retroperitoneal metastasis. If this percentage was greater than 29% the patient was classified as being at high risk. Using this paradigm, 77% of pathologic stage A patients and 91% of pathologic stage B patients were correctly classified. The test efficiency was 82%. This pilot study resulted in an interesting model that should be tested prospectively in consecutive patients to determine whether it is clinically useful.

Aneuploidy↗

The use of conjoint analysis to elicit community preferences in public health research: a case study of hospital services in South Australia.

AIMS: To demonstrate the use of conjoint analysis (CA) in public health research through a survey of the South Australian community about aspects of their public hospital services. METHODS: A series of focus groups determined the most important attributes in choice of hospital services. These were built into a CA survey, using the discrete choice approach. The survey was posted to a representative sample of 700 South Australians. Theoretical validity, internal consistency and non-response bias were all investigated. RESULTS: Some 231 individuals returned the questionnaire. The attribute, 'improvement in complication rates' was positively associated with choice of hospital. Three attributes were found to be negatively associated with such choice: 'waiting times for casualty', 'waiting times for elective surgery' and, anomalously, 'parking and transport facilities'. 'Travel time' and the cost attribute, 'Medicare levy' were not statistically significant. Trade-offs between the significant attributes were estimated, as were satisfaction or utility scores for different ways of providing hospital services. Results concerning internal consistency and internal validity were encouraging, but some potential for non-response bias was detected. CONCLUSION: A high premium is placed on the quality of hospital care and members of the community are prepared to choose between hospitals largely on the basis of outcomes and length of waiting times for elective surgery and in casualty. IMPLICATIONS: CA can yield potentially policy-relevant information about community preferences for health services.

Adult↗

Smoking, body weight, and early-stage endometrial cancer.

The effect of cigarette smoking on the risk of early-stage endometrial cancer was evaluated in a population-based case-control study of women aged 40 to 69 years from upstate New York. Two hundred women with early-stage endometrial cancer diagnosed between 1979 and 1981, and 200 matched community controls were interviewed in person and asked about smoking habits and other risk factors. Statistical analysis revealed a significant decline in relative risk with increased smoking (P less than 0.05). This effect strongly modified the well-known increase in risk with body weight. Among smokers risk did not increase with body weight, whereas among nonsmokers risk increased rapidly with body weight, especially among nonsmokers in whom the peripheral conversion of androgens was the primary source of serum estrogen. Despite this apparent reduced risk for endometrial cancer, smoking remains a major health hazard for women as well as men.

Adult↗

An adaptive hierarchical test procedure for selecting safe and efficient treatments.

We consider the situation where during a multiple treatment (dose) control comparison high doses are truncated because of lack of safety and low doses are truncated because of lack of efficacy, e.g., by decisions of a data safety monitoring committee in multiple interim looks. We investigate the properties of a hierarchical test procedure for the efficacy outcome in the set of doses carried on until the end of the trial, starting with the highest selected dose group to be compared with the placebo at the full level alpha. Left truncation, i.e., dropping doses in a sequence starting with the lowest dose, does not inflate the type I error rate. It is shown that right truncation does not inflate the type I error if efficacy and toxicity are positively related and dose selection is based on monotone functions of the safety data. A positive relation is given e.g. in the case where the efficacy and toxicity data are normally distributed with a positive pairwise correlation. A positive relation also applies if the probability for an adverse event is increasing with a normally distributed efficacy outcome. The properties of such truncation procedures are investigated by simulations. There is a conflict between achieving a small number of unsafely treated patients and a high power to detect safe and efficient doses. We also investigated a procedure to increase power where a reallocation of the sample size to the truncated treatments and the control remaining at the following stages is performed.

Biometry↗

Coefficient alpha: conceptualizations and anomalies.

In this article distinctions are made among some of the different conceptualizations of, and formulas for, Cronbach's coefficient alpha as it is applied to dichotomous or nondichotomous, standardized or unstandardized, and weighted or unweighted data. Issues regarding the statistical significance of alpha and the occasionally encountered anomalies of artificially high alpha and negative values of alpha are given particular attention.

Data Interpretation, Statistical↗

Maternal views on infant hearing loss in a developing country.

BACKGROUND: Parental support for infant hearing loss is essential for a successful infant screening programme. However, in developing countries where unfavourable customs and beliefs towards childhood disabilities have been reported, parental support towards infant screening is uncertain and there is presently no published evidence on the subject. OBJECTIVE: To elicit the views of mothers and would-be mothers in order to ascertain their knowledge on infant hearing loss and their attitudes towards infant hearing screening. METHODS: A structured questionnaire consisting of 15 questions was administered to 101 mothers (mean age 31.6+/-7.3 years, range: 21-55 years) attending two community hospitals in Lagos, Nigeria. The responses were evaluated by descriptive statistics, factor analysis of the principal components and multiple regression analysis. The reliability of the two main domains (knowledge and attitude) was tested for internal consistency by Cronbach's alpha coefficient. RESULTS: Maternal knowledge was highest for measles (73%; mean score 2.54) and ear discharge (73%; mean score 2.51) but low for birth asphyxia (37%; mean score 1.90), traditional medicine (42%; mean score 2.03) and jaundice (47%; mean score 2.09) as causes of hearing loss. Attitude towards neonatal screening was positive in majority of mothers (92%; mean score 2.84) and there was a high acceptance of hearing aids as an early intervention option (84%; mean score 2.70). Five factors (eigenvalue>1) were extracted after principal component analysis with the attitude variables loading highly and exclusively on one factor. Age was the only demographic variable that was associated with a domain (knowledge) after multiple regression analysis. The component scales for the two domains were highly internally consistent (alpha coefficients of 0.84 and 0.83). CONCLUSIONS: Contrary to the concerns often expressed about parental support for infant hearing screening programmes in developing countries, this study suggests that current parental knowledge and attitude favour early detection and intervention of childhood hearing impairment.

Adult↗

Client perceptions of incest and substance abuse.

Clients receiving substance abuse treatment from 35 treatment facilities throughout the United States were surveyed using the Substance Abuse and Incest Survey-Revised (SAIS-R). A total of 732 participants responded to the survey; 518 (71%) were males, 204 (28%) were females, and 10 (1%) did not indicate gender. Participants had a mean age of 33.8 years, were predominately Caucasian (61.6%), never married (45.2%), were currently unemployed (69.4%), and had completed an average of 11.7 years of education. Of the entire sample, 266 (36.3%) reported having been victims of incest; 151 were males and 113 were females (2 did not indicate gender). The group reporting incest histories had a significantly greater percentage of females that did the group not reporting incest histories (chi 2 = 48.1, p < .001). Participants with incest histories were asked about their perceptions regarding incest, substance abuse, and counseling. Item responses were examined using descriptive statistics and factor analysis. The factor analysis on SAIS-R perception items identified five factors that accounted for 68.9% of the variance; these factors were Stigma and Resistance to Counseling; Substance Abuse and Incest; Ambivalence; Fear and Anticipation; and Receptivity to Counseling. Results are presented and the implications for substance abuse treatment and counseling are discussed.

Adolescent↗

Scores and principal components: the relationship between components due to subjects and to variables.

The main purpose of this article is: given a score matrix called S, find out the joint proportional contribution of factors due to persons (conditions, situations, and so forth) and factors due to variables, for any sij observed score, where i identifies persons, and j, variables. This approach makes it possible a) to show that the same score in a given variable may have a different quantitative interpretation in terms of persons or conditions, and b) to find out how subjects differ in the way in which they relate variables.

Confounding Factors, Epidemiologic↗

Do authors of review articles use systematic methods to identify, assess and synthesize information?

PURPOSE: Review articles are an important source of summary information for practising clinicians to assist them in remaining current with the rapidly expanding medical literature. Consequently it is essential that these be of the highest quality. In this study we evaluate, according to published criteria, the methodological quality of review articles (R) including meta-analysis (MA) appearing in a major cancer journal, Journal of Clinical Oncology (JCO), 1983-1995. METHODS: A hand-search of JCO was performed, from the first issue January 1983 through December 1995, to identify R, defined as publications that describe and comment on studies relevant to a specific topic or clinical intervention. Only those dealing with aspects of treatment of human cancer were considered further. Methodological quality was first assessed using 8 criteria proposed by Mulrow, rated independently by two medical oncologists as: specified, unclear or not specified. MA, including studies of dose intensity, were further analyzed according to 23 more detailed criteria proposed by Sacks et al. and rated as adequate, partial or no/unknown compliance. RESULTS: Of 176 review articles, 122 dealt with aspects of treatment of cancer. Compliance with four of Mulrow's eight criteria was generally good, in that 99% clearly stated a purpose, all attempted qualitative synthesis of data. 95% presented a summary and 76% considered future directions. However, in the 106 qualitative reviews (QR), authors rarely gave information on methods of data identification (11.3%), data selection (10.4%) and assessment of validity (8.4%). Structured abstracts seemed to improve the focus and clarity of QR and there was a minor improvement in deficient areas in the later time cohort (1990-1995). Based on 'adequate' compliance with each of the 23 criteria identified by Sacks et al., six dose intensity studies scored 7-12, seven literature data MA scored 10-15 and three individual patient data MA scored 16-18. The highest scores were in the sections relating to prospective design, combinability and statistical analysis. Factors relating to control of bias, sensitivity analysis and application of results were addressed less consistently. CONCLUSIONS: With the exception of MA, the majority of authors contributing reviews to a major cancer journal, JCO, did not use systematic methods to identify, assess and synthesize information. Initiatives such as the Cochrane Collaboration Cancer Network can support and educate clinicians who wish to perform systematic reviews, but quality of reviews would also improve if author, editors and readers systematically applied any of the sets of criteria now available in the literature.

Humans↗

Construct validity in health behavior research: interpreting latent variable models involving self-report and objective measures.

Latent variable models assess the common variance across multiple indicators of a specific construct and are often used when measurement error may bias parameter estimates. However, care must be taken when interpreting the meaning of the latent construct when using item indicators that come from different measurement domains (e.g., self-report and biochemical indicators of smoking). Utilizing simulated data, we demonstrate that even though a model may be considered to have a "good fit" based on conventional criteria, data interpretation may be misleading or erroneous if precautions are not taken when specifying residual covariances. These findings have important implications for health-related research. Whenever different kinds of data are used to define latent variables in a health domain, exactly what items are used, and what biases may be present can affect, sometimes dramatically, (a) the definition of the latent variables and (b) the effects of the latent variables on other variables of interest.

Bias↗

Factor structure and interpretation of the K10.

The Kessler 10 Psychological Distress Scale (K10) is a brief 10-item questionnaire designed to measure the level of distress and severity associated with psychological symptoms in population surveys. It is being used widely, including in the World Health Organization World Mental Health Survey, and as a clinical outcome measure, although little information is available about the structure of the measure. The factorial composition of the K10 was examined in a prospective community survey and cross-validated in a separate large community survey. The K10 was found to consist of 4 factors and a 2-factor second-order factor structure. This was stable across the 2 waves of the prospective study and the Australian National Survey of Mental Health and Well-Being. The 4 factors, labeled Nervous, Negative Affect, Fatigue, and Agitation, were consistent with the original scales from which the items were taken. The 2 second-order factors represent Depression and Anxiety.

Data Interpretation, Statistical↗