Resultados de la estructura completa

The survival of patients with SLE has improved significantly over the last forty years with a 10-year survival rate now approaching 90 % (Gladman, 1995). As a consequence of improved survival outcome measures other than death are necessary to assess prognosis. As agreed by experts on SLE the assessment of patients with SLE should hB described by three domains: disease activity, accumulated damage and quality o f life. These measures reflect the impact of disease on the patient. The socioeconomic impact^of SLE, i.e. the cost of caring for SLE patients is another aspect of outcome, which reflects the impact of disease on the provider health care system and the society in general. In this thesis I have attempted to determine the quality of life and health status, disease activity and end organ damage by well established and validated measures in a cohort of patients with SLE. The influence o f sociodemographic, socioeconomic and psychosocial factors as well as disease related ones on these outcome measures was investigated. I also investigated the cost of care by resources used for medical care (direct costs) and loss of income related to disease morbidity (indirect costs) in a smaller cohort of patients with SLE.

In the latter part of this thesis (Chapters 5 and 6) the quality o f life and health status, and end organ damage in a cohort of patients with primary Sjogren’s syndrome, another autoimmune rheumatic disease closely linked to SLE, were determined and compared to patients with SLE and SLE with secondary Sjogren’s syndrome. The predictors of lymphoma development (the most serious aspect of outcome) in patients with primary Sjogren’s syndrome were also investigated.

The im pact of SLE on the patient: Health status

There have been few studies investigating health status in SLE and examining its relationship to sociodemographic and disease related factors. Other factors such as psychosocial and socioeconomic factors may also be important and but these were not studied.

One hundred and ninety five consecutively attending outpatients with SLE at two centres in the U.K. were studied. Patients with SLE had a poorer quality o f life than a healthy population with respect to all aspects of health. The most consistent determinants of health status were disease activity and social support. Higher disease activity was associated with worse physical function, role physical function, more pain, worse general health, less vitality and worse social function. Greater social support was associated with better physical function, less pain, better general health, more vitality, better social function, role emotional function and mental health. Greater organ damage determined worse physical function and general health. Greater general satisfaction with medical care was associated with better general health.

In summary, SLE has a significant impact on patients’ health status and this may be improved by increasing patients’ social support and satisfaction with health care as well as controlling disease activity and preventing end organ damage.

The im pact of SLE on the patient: Disease activity and dam age

A number of sociodemographic, socioeconomic and disease related factors have been examined as possible factors affecting prognosis in SLE with somewhat controversial results. Although race has been shown to be important, it has been difficult to separate the effects of race from socioeconomic status; some studies show SES not raceH(Ginzler et al,

1982, Ward et al, 1995a), others show either race not SES (Reveille et al, 1990) or both determine mortality in SLE (Studenski et al, 1987). Most of these studies were performed in the United States where access to health care is closely linked to income. These studies also used unstable measures of SES and very few considered psychosocial factors.

Outcome was described in terms of mortality by most studies. There was a need to conduct a study in the U.K. examining the relationship between SES, race, psychosocial factors and outcomes as determined by validated measures o f morbidity; disease activity and end organ damage.

One hundred and ninety five consecutively attending outpatients with SLE at two centres in the U.K. were studied. Patients of non-caucasian origin, with longer disease duration, lower level of education and higher disease activity were more likely to have end organ damage. Patients with more damage were more satisfied with interpersonal aspects of their care and their access to care but less satisfied with the amount of time they spent with their doctor. Very long disease duration was weakly associated with higher disease activity. In summary, both race and SES as well as psychosocial and disease related factors were important in determining outcomes in SLE.

These two studies had the limitation of being cross sectional. Some of the explanatory variables such as marital status, social support, and satisfaction with care may have been affected by the disease process itself. Premorbid data is needed on these sorts of variables but retrospective collection of data is prone to recall bias. Another weakness of these studies was the enrolment of outpatients only. By excluding inpatients the impact of disease may have been under estimated. Future prospective, interventional studies are needed to see whether improving psychosocial and socioeconomic circumstances as well as better control o f disease with medical therapies improve outcomes in patients with SLE.

The impact of SLE on the provider health care system and the society in general: Cost of care for patients with SLE

In the current political atmosphere of limited health care budgets, it is increasingly

important to determine the economic consequences o f disease. Although there have been a number of studies evaluating the costs of rheumatic diseases particularly RA, very few studies examined the financial consequences of SLE and none have been conducted in the U.K.

One hundred and seven consecutively attending patients with SLE at a specialist centre in the U.K. were studied. Direct (resources used for medical care), indirect (loss of income related to disease morbidity) and total costs (sum of direct and indirect costs) were determined and the predictors of cost were identified. Total annual cost of caring for patients with SLE was £ 7913. Direct costs were a third and indirect costs were two thirds

of total costs. The components and predictors of costs were also identified. Patients with higher level of education, lower level of physical health and higher disease activity

incurred higher direct, indirect and total costs. Direct costs were also associated with more end organ damage and younger age.

In summary, SLE has a considerable impact on the provider health care system and the society in general. Improvements in medical therapies to reduce disease activity and prevent damage, as well as improvements in physical health are likely |o reduce costs in SLE.

This study had assigned hospital costs mainly based on local data thus reflecting the costs of treating a patient at the study centre. It was not possible to conduct such a detailed direct cost analysis based entirely on national prices due to the lack of such data. It did not include intangible costs (costs of pain and suffering). This method of socioeconomic evaluation, cost analysis, is only a partial evaluation. It does not answer the question of whether the costs are worth paying for. But it is valuable in determining the magnitude of problem and identifying areas for further investigation. This study was the first

prospective cost identification study in SLE in the U.K. It identified the contributors and determinants of costs. The methodology used and the conclusions derived from this study can be applied to other SLE populations. The trination study (the patients described in this thesis are also enrolled in this international study) is ongoing with the aim of determining whether differences in health care systems and resource utilisation determine differences in outcomes in the long term.

The im pact of SS on the patient: Health status and organ dam age

SS is a disease related to SLE and the two conditions can coexist. Although it usually has a benign course with a slow progression over time, patients often complain of many disabling, rather subjective symptoms such as fatigue, pain, physical and mental

dysfunction and problems with social interaction. However this subjective impact of the disease has been investigated by only a few researchers and in a very limited way so far (Bjerrum and Prause, 1990, Barendregt et al, 1998, Gudbjomsson et ab 1993, Malinow et al, 1985). There have been no studies investigating the broad dimensions of health status with a validated instrument. Cumulative end organ damage, another aspect of outcome, has also not been investigated with a validated instrument in patients with pSS before.

Health status and end organ damage were assessed in 37 patients with pSS and compared to 120 patients with SLE and 21 patients with SLE and SS. Patients with pSS had

considerable disability in all aspects of health, particularly pain and fatigue. Their degree of disability was similar to patients with SLE (with or without SS). End organ damage was uncommon in patients with pSS with the exception of oral damage.

This study had the limitation of being cross sectional. There is a need for long term, prospective studies to identify the clinical, sociodemographic, socioeconomic and psychosocial factors which may influence these outcome measures.

Predictors of lymphoma development in pSS

Lymphoma development is the most serious aspect of outcome in patients with SS. The relative risk is up to 44 times that of an age-sex-race and time specific matched control population (Kassan et al, 1978). However there have been very few studies investigating the clinical predictors of this potentially lethal outcome.

The clinical, laboratory and immunogenetic predictors of lymphoma development in a cohort of 72 patients with pSS were investigated. Five patients developed a distinct type of low grade, B cell Non-Hodgkin’s lymphoma called MALT lymphomas. A history of swollen glands, lymphadenopathy and leg ulcers predicted lymphoma development in this cohort.

This study had the weakness o f studying a relatively small number of pSS patients with lymphoma. However these patients were also enrolled in a multicenter European study of 33 patients with pSS and NHL (Voulgarelis et al, 1999). That study showed that malignant NHL seen in patients with pSS are mostly extranodal. Lymphadenopathy, skin vasculitis, peripheral nerve involvement, low grade fever, anaemia and lymphopenia are reported more frequently than in the general SS population. Further long term interventional studies are needed to see whether new or existing medical therapies may influence this serious outcome.

In summary both SLE and SS have a considerable impact on patients’ lives. There is a need for medical therapies particularly in patients with SLE, which control disease activity better with fewer side effects and which reduce permanent damage. Outcome may also be influenced by improving psychosocial and socioeconomic circumstances. Encouraging patient support groups, setting up patient education programmes similar to the ones employed in RA may be the first step towards achieving this goal. The socioeconomic impact of SLE is considerable and this can also be reduced by achieving the above.

Further studies o f SS are also needed to develop more disease specific outcome measures for this condition. Assessment of existing therapies as well as developing new ones which may influence patients’ well being and modify lymphoproliterative process are needed. The recently formed U.K. Sjogren’s interest group aims to develop a disease specific questionnaire and organise a multicenter hydroxychloroquine trial to assess its efficacy in achieving the above.

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