Measuring disease activity and response to treatment in rheumatoid arthritis

Introduction: Effective treatment of rheumatoid arthritis (RA) requires suppression of the underlying inflammation. Measurement of such inflammation, the disease activity, is mandatory to target treatment and maximize outcomes. However, this is not as straightforward as it may seem.

Areas covered: The many tools developed to measure disease activity in RA, from composite scores and patient-reported outcomes, to laboratory markers and imaging are discussed, with a focus on their utility in guiding therapy and assessing response. The complex issues in measuring disease activity in RA, whether in clinical trials or normal clinical practice, and in the context of national guidelines and recommendations, available time, and resources are considered.

Expert commentary: The key to effective management of RA is the rapid suppression of inflammation, ideally to remission, with maintenance of such remission. The aim is to prevent disability and maximize quality of life. Central to this is the ability to determine disease activity (potentially open to suppression) as opposed to damage (irreversible). A variety of measures are currently available, allowing better assessment of response to treatment. In the future, the development of predictive biomarkers allowing targeting of drugs may revolutionize this field and render the tools of today redundant.     

Workplace status and risk of hypertension among hourly and salaried aluminum manufacturing employees

An inverse relationship between workplace status and morbidity is well established; higher job status has been associated with reduced risks of heart disease, hypertension, and injury. Most research on job status, however, has focused on salaried populations, and it remains unclear whether job status operates similarly among hourly workers. Our objectives were to examine whether hourly status itself influences risk of hypertension after adjustment for socioeconomic confounders, and to explore the role of fine-scale job grade on hypertension incidence within hourly and salaried groups. We examined data for 14,999 aluminum manufacturing employees in 11 plants across the U.S., using logistic regression with adjustment for age, sex, race/ethnicity and other individual characteristics. Propensity score restriction was used to identify comparable groups of hourly and salaried employees, reducing confounding by sociodemographic characteristics. Job grade (coded 1 through 30, within hourly and salaried groups) was examined as a more refined measure of job status. Hourly status was associated with an increased risk of hypertension, after propensity restriction and adjustment for confounders. The observed effect of hourly status was stronger among women, although the propensity-restricted cohort was disproportionately male (96%). Among salaried workers, higher job grade was not consistently associated with decreased risk; among hourly employees, however, there was a significant trend, with higher job grades more protective against hypertension. Increasing the stringency of hypertension case criteria also increased the risk of severe or persistent hypertension for hourly employees.     

Labman and Linkman: A data management system specifically designed for genome searches of complex diseases

Two programs have been developed to manage linkage analysis data. The first program, LABMAN, is a comprehensive laboratory data management system organizing pedigrees, blood DNA samples, DNA markers, Southern blot or polyacrylamide gels, autoradiographs, and marker-allele typings generated from these samples. Output includes mendelization checks for genetic incompatibilities in typings and formatted files ready for linkage analysis. LABMAN can also compress highly polymorphic allele systems into smaller allele systems facilitating analysis of large systems. The second program, LINKMAN, provides data management for lod score output from linkage analyses. It reads linkage analysis output files, calculates lod scores by family, associates lod scores with specific marker and family identifiers, and stores these data in a database where they can be combined with lod scores from previous analyses. LINKMAN easily incorporates any of a wide variety of genetic models. It produces formatted output of lod scores by user-specified criteria for reports or as ASCII files for input to other programs. If desired, tests of homogeneity of linkage across families can be run via the HOMOG program [Ott, 1991] and their output included in reports. The programs include features critical for conducting genome searches of complex diseases: They are easy-to-use, well-tested, and reliable. Data from multi-center investigations can be easily combined for analysis. Moreover, they include extensive error-checking capabilities, and they are specifically set up to protect blindness between laboratory workers and data analysts. LABMAN and LINKMAN are currently available free of charge under DOS. © 1994 Wiley-Liss, Inc.     

The relation between EEG and mental development following cardiac surgery performed under simple deep hypothermia in children

In order to assess the accuracy of electroencephalography (EEG), in children who have undergone cardiac surgery under simple deep hypothermia, the relation between IQ or schoolwork achievement and the duration of circulatory arrest was investigated in 75 such children. Abnormal preoperative EEG's were found in 16 per cent of the children while abnormal postoperative EEG's were found in 17 per cent. The children were divided into 4 groups, according to pre- and postoperative EEG results. Schoolwork achievement scores ranged between 3.0 and 3.2, the difference among the groups being insignificant. Moreover, no significant shift in IQ was found among the groups. Finally, regarding the number of children who were able to go on to a higher level of education, including high school the college or university, again no significant differences were found among the 4 groups. In a comparison with the number of such children in neighboring Nagasaki prefecture able to continue on to a higher level of education, no significant differences were seen either. The findings and statistics of this investigation therefore indicate that pre- and postoperative EEG's are not always a reliable reference for assessing the prognosis of cerebral activity.     

CORRELATION OF SKIN POTENTIAL AND SKIN RESISTANCE MEASURES

Simultaneous measurements of skin potential (SP) and skin resistance (SR) obtained from 20 male and 20 female adult subjects during 2 sessions held 2 to 9 days apart were used in studying (1) the correlation of change measurements and prestimulus level in the two measures, and (2) the amount of correlation between SP and SR using both simple difference and residual change scores in which the regression of poststimulus values on initial level (prestimulus) has been controlled. Correlations within Ss and correlations among Ss showed large individual variability, correlation differences between males and females, and high correlation between SP and SR change scores. Although the law of initial value (LIV) seemed to have little applicability to the measurement of electrodermal responses, the results underscored the need to control for contamination of change measures by initial level regardless of direction.     

Development of an EQ-5D Value Set for India Using an Extended Design (DEVINE) Study: The Indian 5-Level Version EQ-5D Value Set

ObjectivesThis study aimed to develop the Indian 5-level version EQ-5D (EQ-5D-5L) value set, which is a key input in health technology assessment for resource allocation in healthcare.MethodsA cross-sectional survey using the EuroQol Group’s Valuation Technology was undertaken in a representative sample of 3548 adult respondents, selected from 5 different states of India using a multistage stratified random sampling technique. The participants were interviewed using a computer-assisted personal interviewing technique. This study adopted a novel extended EuroQol Group’s Valuation Technology design that included 18 blocks of 10 composite time trade-off (c-TTO) tasks, comprising 150 unique health states, and 36 blocks of 7 discrete choice experiment (DCE) tasks, comprising 252 DCE pairs. Different models were explored for their predictive performance. Hybrid modeling approach using both c-TTO and DCE data was used to estimate the value set.ResultsA total of 2409 interviews were included in the analysis. The hybrid heteroscedastic model with censoring at ?1 combining c-TTO and DCE data yielded the most consistent results and was used for the generation of the value set. The predicted values for all 3125 health states ranged from ?0.923 to 1. The preference values were most affected by the pain/discomfort dimension.ConclusionsThis is the largest EQ-5D-5L valuation study conducted so far in the world. The Indian EQ-5D-5L value set will promote the effective conduct of health technology assessment studies in India, thereby generating credible evidence for efficient resource use in healthcare.     

Criteria for intensive care unit admission and severity of illness

Intensive care is a specialist area of the hospital with concentration of resources and expertise to look after critically unwell patients. No set criteria exist for admission to intensive care, although patients usually have severe illness associated with physiological dysfunction and actual or impending organ failure. There are multiple scoring systems designed to assess severity of illness, all with significant limitations. The National Early Warning Score 2 (NEWS-2) is a commonly used ‘track and trigger’ system designed to detect and respond to the unwell or deteriorating patient. NEWS-2 is marker of physiological disturbance and high scores correlate with intensive care admission and mortality. Looking at the elective and emergency surgical population, patients at high risk of complications should be admitted to intensive care postoperatively. Increasing age, comorbidities, poor exercise tolerance and major surgical intervention are associated with adverse outcomes. Admission to intensive care often requires difficult time-critical decisions to be made with limited information. Intensive care admission can be the difference between life and death, but there are both physical and psychological harm associated with invasive organ support. The four pillars of medical ethics – autonomy, beneficence, non-maleficence and justice – can be used to guide these decisions.