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Developing a scoring system to quality assess economic evaluations.

The number of economic evaluations is constantly increasing. The need to establish a framework with which to assess the validity of the studies has led to the development of checklists and scoring systems to compare the quality of different studies and ensure that decisions made by decision makers and researchers are based on solid evidence. The most prominent of these checklists is that produced by Drummond et al. Their checklist aims to answer two important questions: is the methodology employed in the study appropriate and are the results valid? In this paper three methods using the checklist of Drummond et al. are developed to assess the quality of a random sample of 50 papers selected from the NHS Economic Evaluation Database. Method 1, a direct application of the checklist calculates an average score with each of the ten items weighted equally, this method proves to be good at identifying low quality studies but is a rather a blunt tool for differentiating between high-quality studies. Method 2, also using an additive score, introduces a hierarchy of the effectiveness data and also adds a new item with respect to the transferability of the results. With this method the number of papers scoring top marks decreases dramatically in comparison to method 1. Method 3 involves a multiplicative rather than additive scoring system, which is better at distinguishing between good quality studies but appears to reduce discrimination between poor-quality studies. Overall, the ten-point checklist of Drummond et al. is a useful and quick tool with which to assess the quality of economic evaluations and to enable decision makers and researchers to focus upon the most relevant studies.

Journal Article↗

Factors that influence women's nutrition knowledge in Saudi Arabia.

We studied knowledge of nutritional needs during pregnancy and lactation in 150 pregnant Saudi women at three primary health care centers in Riyadh, Saudi Arabia. We used an interview schedule to collect data regarding the women's knowledge and to determine the effects of certain independent variables on the knowledge scores. Green et al.'s (1980) PRECEDE model provided the theoretical framework for the study. Descriptive statistics, t test, and chi-square methods were used to analyze the data. The majority of the women had poor nutrition knowledge scores, with no significant differences among the three centers. A positive relationship was found between knowledge score and educational level. Negative relationships were found between knowledge score and number of pregnancies, number of deliveries, and number of living children. The findings have several implications for efforts to improve the health status of women in Saudi Arabia.

Adult↗

Construction of a high-resolution linkage map for Xp22.1-p22.2 and refinement of the genetic localization of the Coffin-Lowry syndrome gene.

The genes responsible for two X-linked diseases, the Coffin-Lowry syndrome (CLS) and juvenile retinoschisis (RS), have been previously mapped, through linkage studies, to an 8-cM region, in Xp22.1-p22.2, flanked distally by two tightly linked markers, DXS207 and DXS43, and proximally by DXS274. In the present study, five Genethon markers have been assigned to the (DXS207, DXS43)-DXS274 interval using somatic cell hybrids and a meiotic breakpoint panel and ordered together with three markers previously mapped to this region. A genetic map, which includes 13 loci and spans a distance of approximately 13 cM, was derived from linkage analysis using the CEPH families. The most likely locus order and map distances (in centimorgans) are Xpter-DXS16-(3.4)-(DXS207, DXS43, DXS1053)-(2.0)-(DXS999, DXS257)-(1.7)-AFM291 wf5-(1.4) - DXS443 - (2.0) - (DXS1229, DXS365) - (2.1) - (DXS1052, DXS274, DXS41)-Xcen. Analysis of multiply informative crossovers established AFM291 wf5 and DXS1052 as new flanking markers for CLS, which significantly reduces the candidate region for this disease gene to a 4- to 5-cM interval. Three markers, DXS443, DXS1229, and DXS365, mapping within this interval showed complete cosegregation with the disease phenotype, giving a multipoint lod score of 14.2. The present map provides the framework for constructing a YAC contig for the CLS and RS region and should be useful for refining the localization of other disease genes mapping to this region. The panel of somatic cell hybrids characterized for the present study has also allowed us to refine the localization of five genes (CALB3, GRPR, PDHA1, GLRA2, and PHKA2) and two expressed sequence tags (DXS1118E and DXS1006E) previously assigned to the Xp22 region.

Abnormalities, Multiple↗

Assessment of strategies in families tested by Finnish families.

The aim of this paper was to describe testing a Finnish version of the assessment of strategies in families (ASF) instrument and its construct validity and reliability in Finnish families. The ASF instrument is based on Friedemann's framework of systemic organization and the version used in this study consists of 25 items, each containing three statements. The instrument was developed to estimate family functioning in reaching the four targets of the framework of systemic organization. It provides sub-scores for the targets, family stability (system maintenance and coherence), family growth (system change and individuation), control (system maintenance and system change) and spirituality (individuation and coherence). Data were collected from patients attending the outpatient clinics of pulmonary and rheumatic diseases (N=196). Questionnaires were given to patients capable of understanding the questions and they returned questionnaires by mail directly to researchers. Construct validity was tested with exploratory factor analysis. Factor analysis was done with 22 items. The four factor solution was best suited. Two items were eliminated because of low factor loadings and crossloading. The total of 20 items were left in the instrument. Crohnbach's alpha was used to measure internal consistency. It was computed for each target separately and the total tool. There were discrepancies in the assignment of process dimensions which were expected because of cultural perceptions. The total instrument had a reliability of 0.85. The result of the analyses was a pretested tool with subscales for stability, growth, control and spirituality that have acceptable reliability and concept validity. Less satisfactory was the small number of items representing individuation. Another weakness is the lack of statistical distinction between system maintenance and coherence. The instrument is also usable in these subscales, but it needs further development and retesting. Items need to be added to express individuation, possibly some others. The new items will be formulated freely, paying attention to culture. However, the tool appears good enough to be used as measurement in various research studies.

Adaptation, Psychological↗

Structure comparison and structure patterns.

This article investigates aspects of pairwise and multiple structure comparison, and the problem of automatically discover common patterns in a set of structures. Descriptions and representation of structures and patterns are described, as well as scoring and algorithms for comparison and discovery. A framework and nomenclature is developed for classifying different methods, and many of these are reviewed and placed into this framework.

Algorithms↗

Development of the public health nursing competency instrument.

This paper describes the development and initial testing of an instrument to measure population-based public health nursing competencies. Although multiple lists of public health competencies exist, literature review did not elicit a valid instrument that could measure changes in public health nursing competency over time. The public health nursing competency instrument, consisting of 195 measurable activities organized in the framework of the nursing process, was developed. Competency scores of practicing public health nurses significantly increased after a continuing education series, and the instrument was confirmed by experts to be a valid reflection of public health nursing practice. The time required for instrument development exceeded expectations because of the multiple stages of delineating competencies and validating data with national experts.

Clinical Competence↗

Using case studies to evaluate students' ability to develop a geriatric interdisciplinary care plan.

The Geriatric Interdisciplinary Team Training (GITT) program, an educational intervention funded by The John A. Hartford Foundation of New York City, has trained more than 1800 health care professions students and clinicians throughout the United States. Evaluating the effectiveness of this training intervention has proven to be quite a challenge. Core measures were collected pre- and post-GITT training to evaluate student development as a result of GITT. This paper focuses on one of these core measures, the Test of Geriatric Interdisciplinary Care Planning (TGICP). This instrument, developed for the GITT program, is one mechanism created to test trainees' ability to develop an interdisciplinary plan of care. Using a case study methodology, this two-part instrument provides an innovative approach to quantifying and correlating responses from an interdisciplinary cohort of students. This paper will describe the development of the TGICP, including the creation and validation of the case studies, the framework for the questionnaire, and the coding and scoring mechanism created to evaluate trainee responses.

Aged↗

Life-cycle assessment as an environmental management tool in the production of potable water.

The environmental life cycle assessment (LCA) methodology was used in this study to calculate and compare the environmental burdens resulting from two different methods employed in the production of potable water in South Africa. One method employs conventional processes for the treatment of water and the other one is based on membrane filtration. All inputs (raw materials and energy) and outputs (products, by-products and emissions to air, water and soil) from the two methods were listed and quantified. These inputs and outputs cause different environmental impacts (global warming, ozone depletion, smog formation, acidification, nutrient enrichment, ecotoxicity and human toxicity) and the contribution of each method to each of these impact categories has been quantified, resulting in a score. The ISO (International Organisation for Standardisation) methodological framework for life cycle assessments guided this study. By using these methodologies and by tracing all the processes involved in the production of potable water to the interface with the environment, it was found that the main contributor to the overall environmental burden is the generation of electricity. This conclusion is valid for both methods investigated and in order to increase the environmental performance in the production of potable water the energy efficiency of waterworks should be increased.

Environment↗

Quality of care in family planning services in Morocco.

This study was conducted to heighten awareness of quality of care as a programmatic issue in the Moroccan governmental family planning program and to test modified Situation Analysis instruments for measuring quality of care. Data were collected from 50 service-delivery points in five provinces to measure six elements of quality in accordance with the Bruce/Jain framework. A procedure for calculating quality-indicator scores is presented. Although facilities varied by province and within provinces, most had the equipment and supplies needed to deliver services; service personnel were trained and regularly supervised; the service-delivery points scored well on mechanisms to ensure continuity of use. Notable shortcomings included a dearth of materials for counseling and a widespread unavailability of the Ovrette pill. This study raises issues regarding the complexity of measuring quality, the ownership of results, and the appropriateness of a centralized study of quality in a decentralized program.

Adult↗

Cognitive functioning and anhedonia in subjects at risk for schizophrenia.

This study investigated the performance of individuals with familiar loading of schizophrenia (healthy siblings of schizophrenic inpatients) on three neuropsychological tasks assumed to require frontal lobe functions: Trail Making Test (TMT), verbal fluency and Wisconsin Card Sorting Test (WCST). Healthy siblings of schizophrenics differed in performance from healthy controls not only on the WCST, but also on the Trail Making Test and the verbal fluency task. Furthermore, scores of physical anhedonia, assessed in a self-report rating scale (Chapman et al., 1976) were also significantly higher in the high risk group than in the control sample. However, healthy siblings of schizophrenics did not differ from controls with regard to experiences of perceptual aberrations, measured by the same method (Chapman et al., 1978). Neuropsychological performance and elevated anhedonia scores in the high risk group were interpreted under the conceptual framework of vulnerability markers: they were supposed to represent a trait shared by family members of schizophrenic probands. Amongst the neuropsychological tests, there were significant correlations between the physical anhedonia score and WCST and Trail Making test performance in the group of healthy siblings of schizophrenics, but not in the control group.

Adult↗

Combining evolutionary and structural information for local protein structure prediction.

We study the effects of various factors in representing and combining evolutionary and structural information for local protein structural prediction based on fragment selection. We prepare databases of fragments from a set of non-redundant protein domains. For each fragment, evolutionary information is derived from homologous sequences and represented as estimated effective counts and frequencies of amino acids (evolutionary frequencies) at each position. Position-specific amino acid preferences called structural frequencies are derived from statistical analysis of discrete local structural environments in database structures. Our method for local structure prediction is based on ranking and selecting database fragments that are most similar to a target fragment. Using secondary structure type as a local structural property, we test our method in a number of settings. The major findings are: (1) the COMPASS-type scoring function for fragment similarity comparison gives better prediction accuracy than three other tested scoring functions for profile-profile comparison. We show that the COMPASS-type scoring function can be derived both in the probabilistic framework and in the framework of statistical potentials. (2) Using the evolutionary frequencies of database fragments gives better prediction accuracy than using structural frequencies. (3) Finer definition of local environments, such as including more side-chain solvent accessibility classes and considering the backbone conformations of neighboring residues, gives increasingly better prediction accuracy using structural frequencies. (4) Combining evolutionary and structural frequencies of database fragments, either in a linear fashion or using a pseudocount mixture formula, results in improvement of prediction accuracy. Combination at the log-odds score level is not as effective as combination at the frequency level. This suggests that there might be better ways of combining sequence and structural information than the commonly used linear combination of log-odds scores. Our method of fragment selection and frequency combination gives reasonable results of secondary structure prediction tested on 56 CASP5 targets (average SOV score 0.77), suggesting that it is a valid method for local protein structure prediction. Mixture of predicted structural frequencies and evolutionary frequencies improve the quality of local profile-to-profile alignment by COMPASS.

Algorithms↗

The ethical appropriateness of using prognostic scoring systems in clinical management.

The four ethical principles of beneficence, nonmaleficence, autonomy, and social justice provide a framework for making medical decisions, including those that involve the administration of life-sustaining therapies. In recent years, a number of prognostic scoring systems, including the Acute Physiology Assessment and Chronic Health Evaluation (APACHE) system, have been developed to augment clinical judgment in determining which critically ill patients are likely to benefit from such therapies. Although these systems all have limitations, their use in decision making is as ethically appropriate as is the use of clinical judgment, which has its own limitations and has been used for years.

AIDS-Related Opportunistic Infections↗

What does the PANSS mean?

OBJECTIVE: Despite the frequent use of the Positive and Negative Syndrome Scale (PANSS) for rating the symptoms of schizophrenia, the clinical meaning of its total score and of the cut-offs that are used to define treatment response (e.g. at least 20% or 50% reduction of the baseline score) are as yet unclear. We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions (CGI). METHOD: PANSS and CGI ratings at baseline (n = 4091), and after one, two, four and six weeks of treatment taken from a pooled database of seven pivotal, multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking. RESULTS: Being considered "mildly ill" according to the CGI approximately corresponded to a PANSS total score of 58, "moderately ill" to a PANSS of 75, "markedly ill" to a PANSS of 95 and severely ill to a PANSS of 116. To be "minimally improved" according to the CGI score was associated with a mean percentage PANSS reduction of 19%, 23%, 26% and 28% at weeks 1, 2, 4 and 6, respectively. The corresponding figures for a CGI rating "much improved" were 40%, 45%, 51% and 53%. CONCLUSIONS: The results provide a better framework for understanding the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations. Such studies may ideally use at least a 50% reduction from baseline cut-off to define response rather than lower thresholds. In treatment resistant populations, however, even a small improvement can be important, so that a 25% cut-off might be appropriate.

Adult↗

A framework to infer de novo exonic variants when parental genotypes are missing enhances association studies of autism.

MOTIVATION: Gene-damaging mutations are highly informative for studies seeking to discover genes underlying developmental disorders. Traditionally, these de novo variants are recognized by evaluating high-quality DNA sequence from affected offspring and parents. However, when parental sequence is unavailable, methods are required to infer de novo status and use this inference for association studies. RESULTS: We use data from autism spectrum disorder to illustrate and evaluate methods. Separating de novo from rare inherited variants is challenging because the latter are far more common. Using a classifier for unbalanced data and variants of known inheritance class, we build an inheritance model and then a de novo score for variants when parental data are missing. Next, we propose a new Random Draw (RD) model to use this score for gene discovery. Built into an existing inferential framework, RD produces a more powerful gene-based association test and controls the false discovery rate. AVAILABILITY AND IMPLEMENTATION: Codes are available at Github (https://github.com/HaeunM/TADA-RD) and Zenodo (DOI: https://doi.org/10.5281/zenodo.18531769).

Humans↗

Predicting adolescent risk behaviors based on an ecological framework and assets.

OBJECTIVES: To examine the relationship between an aggregate risk score (smoking, drinking, and number of sex partners) and measures of youth assets in a sample of 3439 youth aged 14-18 years. METHODS: Linear regression models for African American and white males and females predicted an aggregate risk score. RESULTS: After adjustments, the youth asset most predictive of risk was self/peer values regarding risk behaviors. Perceived school support was also predictive. CONCLUSIONS: Taking an ecological approach to the measurement of adolescent health behaviors contributes to our understanding of these risk behaviors.

Adolescent↗

Can we identify the poorest quality of life? Assessing the importance of quality of life using the WHOQOL-100.

In this study, WHOQOL survey data obtained from 4802 sick and well participants in 15 countries were used to investigate the relationship between judgements about different dimensions of quality of life (QOL) (core scores) and the importance attributed to them. As a theoretical framework, we applied the WHOQOL Group's (1995) definition of QOL which indicates that those who report the very poorest QOL will be least likely to have met their own '...goals, expectations, standards and concerns'. Those with the poorest QOL would therefore be expected to show the biggest difference between core and importance scores, and therefore be distinguishable from respondents whose QOL was poor, better or best. The main effects from overall analyses confirmed that those reporting the largest negative differences tended to report the poorest QOL and also attached a high degree of importance to these dimensions. Evidence for a decreasing differential across the four groups (poorest to best) was confirmed for the majority (18) of facets. However facet level analyses comparing groups with different levels of QOL showed that only five facets distinguished those with the poorest QOL from those whose QOL was poor, so the theory is not well supported. Furthermore the contribution of core-importance facet differences reduced the overall prediction of QOL, when compared with a regression of core scores alone. Importance information about specific facets may have limited potential to be used alongside the main instrument to identify areas of the poorest QOL for clinical or social action.

Adult↗

Score tests for homogeneity of regression effect in the proportional hazards model.

A simple model, containing the proportional hazards regression model as a special case, is presented. The purpose of the model is to provide a framework in which specific alternatives to the proportional hazards assumption may be tested. Rank-invariant score tests for linear, quadratic, or exponential trends can, for instance, all be undertaken within this framework. In the case of the two-sample problem the required calculations are shown to take a particularly simple form. Special consideration is given to the two-sample case in which there is an inversion of the regression effect, i.e., where the hazard functions cross at some given point. Both of the motivating examples are concerned with this problem. Computational aspects are relatively straightforward and some discussion on this is provided.

Actuarial Analysis↗

Kv11.1 (hERG) Protein Interaction Networks Connect Endocytic Trafficking to Polygenic Influences on Cardiac Repolarization.

Polygenic scores (PGS) capture the combined effect of many common genetic variants on quantitative traits and disease risk, yet their functional consequences at the protein level remain poorly defined. Here, we integrated quantitative and interaction proteomics to resolve how polygenic liability for cardiac repolarization manifests in human cells. We studied human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from donors with extreme PGS for QT interval duration, a clinically relevant electrophysiologic trait associated with arrhythmia risk. Global quantitative proteomics revealed increased abundance of mitochondrial proteins in high-PGS cardiomyocytes. To define protein network-level effects on a key repolarizing ion channel, we performed multiplexed affinity purification-mass spectrometry (AP-MS) of Kv11.1. While mitochondrial changes did not directly explain Kv11.1-associated complexes, interactome analysis revealed increased association of Kv11.1 with myosin motor proteins and endosomal recycling machinery in high-PGS cells. These findings suggest altered channel trafficking dynamics of Kv11.1, distinct from the trafficking defects observed in monogenic Kv11.1 variants. Together, these data show that integrating global and interaction proteomics can resolve how polygenic variation reshapes protein networks. Future work using these methods could connect genomic risk to subcellular remodeling and our work provides a generalizable framework to probe the proteomic basis of complex traits. SIGNIFICANCE STATEMENT: Polygenic scores (PGS) predict disease risk, but how biological pathways are influenced by these common variants remains difficult to define. We generated human induced pluripotent stem cells from individuals with extreme high- and low- PGS for QT interval, a key electrocardiographic measure linked to arrhythmia risk. By combining global proteomics and interactomics for a common ion channel involved in regulating the QT interval (Kv11.1) we found potential mechanisms that are influenced by common genetic traits in patients. Our work provides an approach to connect polygenic scores to pathway-level molecular mechanisms in human cells and a general framework for uncovering how complex genetic architecture drives disease-relevant biology.

AP-MS↗