The impact of leprosy on the mental wellbeing of leprosy-affected persons and their family members - a systematic review.

Leprosy has long-term consequences related to impairment and stigma. This includes a major impact on mental health. This study aims to consolidate current evidence regarding the mental health impact of leprosy on affected persons and their family members. In addition, determinants influencing mental health outcomes among leprosy-affected persons and effective interventions are examined. A keyword-based search was conducted in PubMed, Web of Science, Scopus, PsycINFO, Infolep and InfoNTD; additional literature was also considered. Articles presenting primary data involving leprosy-affected persons or their family members experiencing mental conditions were included. Independent extraction of articles was executed using predefined data fields. Articles were sorted according to relevance. In total, 65 studies were included in this systematic review. Multiple psychiatric morbidities have been identified among leprosy-affected persons, including depression, anxiety disorders and suicide (attempts). Additional factors were found that may impact mental health. Moreover, studies found that demographic factors, lifestyle and disease-specific factors and stigma and discrimination impact mental health. Depressive symptoms and low self-esteem were identified among children of leprosy-affected persons. In addition, interventions were identified that could improve the mental wellbeing of leprosy patients. Depressive disorders and anxiety disorders were found to be very common among persons affected by leprosy. Feelings such as fear, shame and low self-esteem are also experienced by those affected, and their children. Further research is necessary to ensure that mental health impact is included when determining the burden of disease for leprosy, and to relieve this burden.

Satisfactory cross cultural equivalence of the Dutch WOMAC in patients with hip osteoarthritis waiting for arthroplasty.

BACKGROUND: Cross cultural validity is of vital importance for international comparisons. OBJECTIVE: To investigate the validity of international Dutch-English comparisons when using the Dutch translation of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). PATIENTS AND METHODS: The dimensionality, reliability, construct validity, and cross cultural equivalence of the Dutch WOMAC in Dutch and Canadian patients waiting for primary total hip arthroplasty was investigated. Unidimensionality and cross cultural equivalence was quantified by principal component and Rasch analysis. Intratest reliability was quantified with Cronbach's alpha, and test-retest reliability with the intraclass correlation coefficient. Construct validity was quantified by correlating sum scores of the Dutch WOMAC, Arthritis Impact Measurement Scales (Dutch AIMS2), Health Assessment Questionnaire (Dutch HAQ), and Harris Hip Score (Dutch HHS). RESULTS: The WOMAC was completed by 180 Dutch and 244 English speaking Canadian patients. Unidimensionality of the Dutch WOMAC was confirmed by principal component and Rasch analysis (good fit for 20/22 items). The intratest reliability of the Dutch WOMAC for pain and physical functioning was 0.88 and 0.96, whereas the test-retest reliability was 0.77 and 0.92, respectively. Dutch WOMAC pain sum score correlated 0.69 with Dutch HAQ pain, and 0.39 with Dutch HHS pain. Dutch WOMAC physical functioning sum score correlated 0.46 with Dutch AIMS2 mobility, 0.62 with Dutch AIMS2 walking and bending, 0.67 with Dutch HAQ disability, and 0.49 with Dutch HHS function. Differential item functioning (DIF) was shown for 6/22 Dutch items. CONCLUSIONS: The Dutch WOMAC permits valid international Dutch-English comparisons after correction for DIF.

Quality of life profiles in the first years of rheumatoid arthritis: results from the EURIDISS longitudinal study.

OBJECTIVE: The aim of this study was to examine the quality of life (QoL) profiles of patients with early rheumatoid arthritis (RA) and to relate these to disease and impairment variables as indicated, respectively, by erythrocyte sedimentation rate (ESR) and by tender joint count (Ritchie Articular Index), fatigue, and pain. METHODS: The present study uses part of the European Research on Incapacitating Disease and Social Support data of 573 patients with recently diagnosed RA (268 from the Netherlands, 216 from Norway, and 89 from France). A series of clinical and psychosocial data were collected on 4 (the Netherlands, France) and 3 (Norway) occasions, with 1-year intervals separating the waves of data collection. RESULTS: Of the disease activity (ESR) and impairment variables (tender joint count, fatigue, pain), fatigue was identified as the consequence of disease that differentiated best on a series of QoL aspects such as disability, psychological well-being, social support, and "overall evaluation of health." Next came pain and tender joint count, and ESR showed by far the least differentiating ability. A principal-component analysis on the QoL measures used in this study yielded one general factor measuring "overall QoL." After rotation, two separate factors were encountered, one referring to the physical domain and the other to the psychological and social domains of QoL. Again, the QoL of RA patients experiencing much fatigue appeared to decline the most. CONCLUSIONS: Because of the highly variable nature of RA, impairments, activities of daily living (ADL) and instrumental ADL restrictions, and psychosocial distress can vary erratically. In particular, "fatigue" as measured over a period of 2 to 3 years distinguished best among RA patients as shown by their QoL profiles. Although the physical domain was most affected, the significant effect of RA on the psychosocial domain should not be underestimated.

Validation of a German version of the Fibromyalgia Impact Questionnaire (FIQ-G).

OBJECTIVE: To translate the Fibromyalgia Impact Questionnaire (FIQ) into German and to evaluate its reliability and validity for the use of German speaking patients with fibromyalgia (FM). METHODS: We administered the FIQ to 55 patients with FM (15 patients filled out the questionnaire 10 days later) together with German versions of the Stanford Health Assessment Questionnaire (HAQ), the Medical Outcomes Survey Short Form-36 (SF-36), and a tender point count (TPC). All patients were asked about the severity of pain today (10 cm visual analog scale) and the duration of symptoms. Tenderness thresholds were assessed by dolorimetry at all tender points with a Fisher dolorimeter and laboratory tests were obtained. Test-retest reliability was assessed using Spearman correlations. Internal consistency was evaluated with Cronbach's alpha of reliability. Construct validity of the FIQ was evaluated by correlating the HAQ and subscales of the SF-36 as well as the TPC and the tenderness thresholds. RESULTS: Mean age of participants was 54.3 years and mean duration of symptoms 9.5 years. Test-retest reliability was between 0.62 and 1 for the physical functioning as well as for the total FIQ and other components. Internal consistency was 0.92 for the overall FIQ. Significant correlations were obtained between the FIQ items, the HAQ, and the SF-36. CONCLUSION: The German FIQ is a reliable and valid instrument for measuring functional disability and health status in German patients with FM.

The disease process and utilization of health services in rheumatoid arthritis: the relative contributions of various markers of disease severity in explaining consumption patterns.

OBJECTIVE: To examine the predictive ability of a wide array of measures of disease severity in explaining Dutch and German patterns of health services utilization during a 2-year period. METHODS: Slightly over 200 rheumatoid arthritis (RA) patients, 136 from a Dutch and 98 from a German outpatient clinic, supplied information on symptom and functional status, global health, and emotional and social functioning at baseline. The patients' rheumatologists provided clinical assessments of functional grade and disease activity. A questionnaire mailed twice at 12-month intervals was the source of retrospective information on physician consultations, hospitalization, and referrals for surgery and physical therapy during the previous period. Major determinants of use were studied with multivariate analyses. RESULTS: German patients reported more frequent physician contacts than Dutch patients, but the volume of surgery, hospital admissions, and referrals for physical therapy did not differ between the two countries. In a hierarchical regression, the consultation rate was directly associated with pain quality and global health. Markers of RA progression were related to surgery, and the latter to volume of in-hospital care. Fatigue severity and physical disability predicted referrals for physical therapy. Patient self-management activities were only weakly associated with disease severity variables. CONCLUSION: The activity and damage components of RA were related to the separate components of total health service utilization. Disease activity was the prime determinant of physician services used, and RA progression the determinant of surgical interventions and hospitalization.

The social environment and health in rheumatoid arthritis: marital quality predicts individual variability in pain severity.

OBJECTIVE: To examine prospective relations between a wide array of measures of social functioning and pain, while controlling for disease duration and activity and functional grade. METHODS: As part of a larger study on health care utilization, longitudinal data were collected from 136 Dutch and 98 German outpatients on clinical status and pain. Social data included information on sexual handicap, spouse behavior, loneliness, daily emotional support, and the maintenance of pleasurable life domains. Pain severity was assessed at baseline and 12 months later with standard measures of pain and analyzed with hierarchical regressions. RESULTS: Social measures obtained at baseline were consistently associated with pain at followup. Depression was a moderate correlate of pain in the Dutch and German samples. The regressions revealed that patient reports of negative spouse behavior (such as avoidance and critical remarks) and baseline depression predicted worse pain outcome, and this association remained significant in analyses controlling for baseline pain. The level of formal education was a weak correlate of disability, emotional support, and pain. Daily emotional support and social life domains associated with positive affect had an indirect influence on outcome. The absence of strong rather than weak social ties was the component of the loneliness construct linked to pain. These associations between social prognostic factors and pain severity, however, were mediated by psychological functioning at baseline. CONCLUSION: The social environment was found to operate on the core health outcome, pain severity, via several pathways. Social functioning may be affected by rheumatoid arthritis (RA) progression, but it also appears to form a determinant of future health outcome. Not only the status of being married but also the quality of the relationship in terms of long-term stress and emotional support may be useful prognostic factors in RA.

A microsatellite within the MUC1 locus at 1q21 is altered in the neoplastic cells of breast cancer patients.

Paired DNA samples from the neoplastic and nonneoplastic cells of 118 patients with the sporadic, nonfamilial form of breast cancer were analyzed for evidence of genetic alteration at a polymorphic microsatellite mapped to intron 6 within the MUC1 gene at 1q21. Two other microsatellite loci, D1S104 and APO-A2, which also map to 1q21, were analyzed as well. The frequency of alteration at the microsatellite within the MUC1 locus was significantly higher than D1S104 or APO-A2 (P < 0.001). Analysis by Southern blotting of the VNTR region of the MUC1 gene revealed an amplification of one allele in 34 of 54 informative cases (63%). There was no significant association between these alterations and alterations of the microsatellite within the same locus, suggesting independent mechanisms were responsible for the genetic changes. Microsatellite loci D17S579 at 17q21, the site of the BRCA1 gene, and D18S34 at 18q21-qter, the deleted in colorectal cancer locus, were also analyzed by PCR. Alterations at D17S579 and D18S34 were detected in 18.8% and 6.2% of patients, respectively (P < 0.001, and P < 0.1 relative to the frequency of alteration at D1S104 or APO-A2). A previously described polymorphism of hMSH2 was altered in 16.4% of cases.

Interleukin-2-secreting mouse fibroblasts transfected with genomic DNA from murine neoplasms induce tumor-specific immune responses that prolong the lives of tumor-bearing mice.

Genetic alterations are a common feature of the malignant phenotype. Among other properties, altered genes may be responsible for invasion and metastasis, as well as for resistance to chemotherapeutic agents. Under appropriate circumstances, the products of other altered genes expressed by malignant cells may act as tumor-associated T-cell epitopes, capable of provoking antitumor immune responses. As a novel means of augmenting the immunogenicity of the gene products, unfractionated, sheared genomic DNA from various tumor cell lines (B16F1 melanoma, B16F10 melanoma, MOPC-315 plasmacytoma, C1498 lymphoma, or J558 myeloma), or from non-neoplastic liver cells of tumor-free mice, was transfected into LM cells, a mouse fibroblast cell-line (H-2k) that had been modified previously by retroviral gene transfer to secrete interleukin-2 (IL-2). The IL-2-secreting transfected cell populations were then tested for their immunogenic properties toward B16F1 (H-2b) or C1498 (H-2b) cells in syngeneic C57BL/6 mice. The antitumor responses were specific for the type of tumor from which the DNA was obtained. The survival of C57BL/6 mice injected with a mixture of viable B16F1 cells and IL-2-secreting LM cells transfected with DNA from B16F1 cells was significantly prolonged. In a similar manner, the survival of C57BL/6 mice injected with a mixture of C1498 cells and IL-2-secreting LM cells transfected with DNA from C1498 cells was prolonged as well. The immunity was mediated predominantly by CD8+ and natural killer/lymphokine-activated killer (NK/LAK) cells. These data raise the possibility that a cell line altered previously for cytokine secretion may be readily modified to provide immunologic specificity for the neoplasms of individual cancer patients.

["State of the art" in epidemiology of arthroses. An overview of important studies of etiology and sequelae]. / "State of the Art" in der Arthrosenepidemiologie. Ein Uberblick über wichtige Studien zur Atiologie und zu den Krankheitsfolgen.

The term "Osteoarthrosis" encompasses a group of joint disorders characterized by pain and restriction of mobility. Currently, considerable confusion prevails with respect to the definition of the disease entity and the classification criteria to be utilized in epidemiologic research. Despite these methodological difficulties, it is discernible from the international rheumatology journals that during the past decade this emerging field of research has become firmly established in several European countries and in North America. Researchers have focused their attention on four major facets of the disease: 1. etiological or risk factors with respect to the initiation and clinical course of disease, 2. the impact of illness on the individual and his family, 3. the statistical estimation of incidence and prevalence rates in the total population or in selected at-risk groups of individuals, 4. health care utilization patterns and their costs and benefits. This survey article aims at providing a critical overview of this emerging field of research, as well as at suggesting to the reader future lines of development useful for public health and health promotion researchers in Germany.

Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American blacks.

Thyroxine-binding globulin-slow (TBG-S), a variant found in 4-12% of Black and Pacific Island populations, is inherited as an X-chromosome linked trait. This variant is detected on isoelectric focusing by the characteristic cathodal shift of all its isoforms, suggesting that the difference resides in the core protein. In addition, TBG-S is slightly more thermolabile, which explains why subjects expressing TBG-S have on the average lower serum TBG, and thus reduced T4, concentrations. We now report the molecular basis for this TBG variant, deduced from sequencing the TBG-S gene of an American Black man. Sequencing of the four coding regions and all intron/exon junctions revealed a single nucleotide substitution in the codon for amino acid 171 of the mature protein. The resulting change of the codon GAC to AAC results in replacement of the normal aspartic acid by asparagine. Since the negative charge provided by the aspartic acid is lost when replaced by the neutral asparagine, this substitution seems responsible for the cathodal shift on isoelectric focusing and slower electrophoretic mobility of TBG-S. An identical nucleotide substitution was identified in an unrelated American Black man expressing TBG-S. Whether the TBG-S phenotype observed in populations from the Pacific Islands is caused by the same mutation remains to be determined.

[Long-term anxiety and depression following myocardial infarct]. / Langfristige angst und Depressivität nach Myokardinfarkt.

Data from the 5-year Oldenburg Longitudinal Study were used for investigating the causes of differences in psychological well-being in a national sample of 1000 cardiac patients. In a subsample of 400 married patients, for whom data from the spouse were available, exogenous influences, cognitive mediators, and two measures of psychological distress were linked up in models explaining/predicting the level of anxiety and depression. A major hypothesis was the salience of the illness-related cognitions of the patient as a determinant of long-term behavior and mood state. Early patient subjective health perceptions, the 'primary appraisal' of threat/harm/loss, were found to be the most important predictors of subsequent psychological well-being at the fourth wave of the study several years later. As an instrument for patient screening and psychosocial intervention, Type A's and other groups of subjects seemed to constitute high-risk patient groups.

Marriage and the psychological consequences of a heart attack: a longitudinal study of adaptation to chronic illness after 3 years.

As part of a larger study on recovery from myocardial infarction in a national sample of male cardiac patients, data was collected on slightly under 400 men and their wives over a 5-year period. This longitudinal data set was used to investigate the role of patient health cognitions and marital factors on long-term psychological response to the illness. Negative appraisals of threat and loss due to cardiac impairment/disability were found to be the best predictor of anxiety and depression at 3-4 years after hospitalisation. Patient cognitions appeared to be a chief mediator of medically-defined illness. Supportive marital environments were defined by scales measuring intimate attachment and spouse conflict. The latter was found associated with negative health cognitions and elevated anxiety. High intimacy marriages appeared to provide adequate social support, and the level of intimacy between the spouses was inversely related to the level of depressed mood. These findings were suggestive of a buffering effect of the patient's social support system. Other predictors, including the type A pattern, 'vital exhaustion', and social class were investigated as components of a multifactorial model for clinical screening purposes.

Marital context and post-infarction quality of life: is it social support or something more?

The development of a theory of quality of life following serious illness is currently an important field of endeavour in rehabilitation research. The interpersonal relationships of people and elements of the self-concept appear to be salient factors in causal models of subjective well-being. One such model developed to explain characteristic levels of well-being was used in a longitudinal study of adaptation to a first myocardial infarction. Data were collected from a national sample of male cardiac patients and their spouses on the illness and marital situation as predictors of long-term well-being or ill-being. Analyses of data from the first three waves of the study, which is to extend over 5 years after the onset of illness, are to be discussed in the paper. Marital status, the emotional quality of the spouse relationship and long-standing marital stressors were found to have direct and indirect effects on the two dimensions of the Bradburn Affect Balance Scale. The same is true of continuing problems associated with the heart attack relative to perceptions of having coped effectively with the after effects of illness. Differences in self-esteem and personal competence were suggested as mediators of socio-environmental and illness-related influences. The two-factor conception of well-being developed was found to be a useful framework for investigating positive and negative aspects of psychosocial rehabilitation. The same factors that explain differences between happy and unhappy people in social indicators research also appeared to be determinants of different trajectories of adaptation in the wake of a life-threatening illness. Previous research using theoretical models from stress research has overemphasized psychosocial morbidity and stress management and neglected positive processes of adaptation. The identification of love resources related to positive feeling states and life satisfaction has, therefore, not received the attention it deserves. This is especially the case regarding an overemphasis of the concept of social support as a buffer of stress. Instruments were developed to measure high and low marital intimacy, as well as chronic marital role strains, and these measures appeared to explain different trajectories of adjustment to cardiac disease. The two-factor model appears to be useful for future work on quality of life with chronic illness. The same is true of four marital contexts of rehabilitation that were identified in the study.

Cancer from a biobehavioural and social epidemiological perspective.

Malignant neoplasm should not be viewed as a 'psychogenic' nor as a 'primarily organic' disease but as an interaction of various forces, in which psychosocial factors may play an important role. To understand the increase in neoplastic disease, which has taken place in this century, requires a theoretical framework including social, psychosocial and behavioural dimensions, as well as the endocrine and immunologic mechanisms acting as pathogenic pathways. Recent theoretical developments in health psychology and allied disciplines on coping behaviour and social support should be integrated into biomedical models of the aetiology, pathogenesis and clinical course of malignant neoplasia. Environmental stressors, as well as mediating variables at the cognitive, affective, behavioural and physiological levels of adaptation, are suggested as major components of a model of multidimensional pathology. A growing body of research on the role of psychosocial factors in adjustment to cancer and its treatment has contributed new insights into possible variables and causal mechanisms which may be relevant in the aetiology of the disease. Closeness to parents in childhood and the ability to form close interpersonal relationships in later adult life very possibly influence the ability of the individual to cope effectively with environmental stressors prior to neoplastic disease and with the considerable stresses of being a cancer patient subsequent to diagnosis and treatment. Pathogenic pathways for future investigation include mental health variables, such as self-esteem and sense of control, at the psychological level and immunity surveillance at the biological. An integration and cross-fertilization of current work in the aetiology of and adjustment to cancer is suggested linking psychosomatic and somatopsychic models.