Characteristics of primary biliary cirrhosis in British Columbia's First Nations population.

Primary biliary cirrhosis (PBC) is a rare, autoimmune liver disorder characterized by progressive destruction of intrahepatic bile ducts, that results in portal inflammation, scarring, cirrhosis and, eventually, liver failure. Although considered rare in Canadian populations, it is the leading indication for referral for liver transplantation in British Columbia's First Nations population. Previously, an expanded review of all cases referred to the British Columbia Transplant Society for PBC was carried out comparing the demographics of those of First Nations descent with those not of First Nations descent. The review suggested that the rate of referral for transplantation was eight times higher for those of First Nations descent compared with those of other descent (P=0.0001), and a disproportionate number of the First Nations cases lived on Vancouver Island (48% of cases versus 18% expected, P<0.05). Additionally, the age of referral was significantly younger (45.9 versus 54.3 years) for those of First Nations descent and there are fewer First Nations men referred (1:34) than expected. For the purpose of the present report, 28 symptomatic cases were ascertained separately and reviewed in a clinical study to delineate the features of this population. RESULTS: Although available liver biopsy reports were consistent with PBC, not all cases were antimitochondrial antibody-positive (18% negative). There was a family history of PBC confirmed by medical records in 33% of cases. There were five multiplex families identified, one with seven affected individuals. Detailed family histories revealed a recurrence risk of 4% for PBC for all first-degree relatives older than 21 years of age, but 10% when considering only women. Other autoimmune conditions coexisted in PBC patients in 79% of all cases. Arthritis was most frequent (60%), with thyroid disease (16%) and systemic lupus erythematosus (12%) also present. Additionally, a history of autoimmune diseases (arthritis, systemic lupus erythematosus and thyroid disease) was present in 21% of first-degree relatives. A strong genetic predisposition to PBC and other autoimmune diseases, combined with common environmental factors, is postulated in this population. Further study is underway to identify these factors.     

Pilot clinical trial of intravenous doxycycline versus placebo for rheumatoid arthritis

OBJECTIVE: To screen for potential efficacy and assess the feasibility of intravenous (IV) doxycycline as a treatment for rheumatoid arthritis (RA). METHODS: The study was a (stratified, block) randomized, double blind, 12 week, pilot trial of IV doxycycline 300 mg/day versus identical appearing IV placebo given over 2 h for 14 days. The primary comparison was to a hypothesized placebo rate of 20% as described by Paulus. If a total of 14 consecutive subjects receiving doxycycline treatment did not respond, it would be considered futile to proceed to a Phase III trial. We planned a placebo group of 14 subjects to verify the placebo response rate and estimate sample size required for a definitive Phase III trial, if such a trial was warranted based on the pilot study. American College of Rheumatology (ACR) RA response criteria were used. After 23 subjects entered, the study was closed due to recruitment difficulties. RESULTS: At baseline, mean (SD) tender joint count was 37 (11.9), swollen joint count 30 (9.6), morning stiffness 317 (319) min, and erythrocyte sedimentation rate 72 mm/h (27.5). Randomization resulted in 10 subjects receiving doxycycline and 13 receiving placebo. Treatment was stopped in 8 subjects: in 6, treatment was ineffective (one taking doxycycline, 5 placebo), and in 2, rashes occurred (one taking doxycycline, one placebo). Only one subject met ACR response criteria in the doxycycline group and none in the placebo group. Having no responders in the placebo group was consistent with placebo response rate of 20% or less. Several patients required peripherally inserted central catheters for venous access. CONCLUSION: The efficacy of IV doxycycline as a treatment for RA could not be ruled out. However, as the proportion of responders was small, it is unlikely that potential efficacy of IV doxycycline would outweigh potential disadvantages of IV administration.     

Autoantibodies against the Beta- and Muscarinic Receptors in Cardiomyopathy

The sera of patients with idiopathic dilated cardiomyopathy and the Chagas' disease contain agonist-like autoantibodies directed against the beta 1-adrenoceptor and/or the muscarinic M2-receptor. The anti-beta 1-adrenoceptor antibodies could be directed against amino acid sequences of the first or second extracellular loop. In patients with dilated cardiomyopathy the first as well as the second extracellular loop was identified as an antibody epitope. In Chagas' disease the anti-beta 1-adrenoceptor antibody recognizes only 1 epitope on the second extracellular loop. The anti-beta 1-adrenoceptor antibodies acting like the beta-adrenergic agonist isoprenaline and exert a positive chronotropic effect in cultured rat cardiomyocytes. In contrast to isoprenaline the antibody caused no downregulation of the beta-adrenergic signal transduction cascade within 6 hours. The anti-M2 receptor antibodies recognize in both diseases an epitope on the second extracellular loop. The anti-M2-receptor antibody exert a negative chronotropic response in cultured cardiomyocytes. This antibody induced no downregulation of the muscarinic M2-receptor. The negative chronotropic effect was unabated for 6 hours. Based on these findings it is believed that the agonist-like autoantibodies that act against the beta 1-adrenoceptor and the muscarinic M2-receptor may play a role in the pathogenesis of dilated cardiomyopathy and Chagas' disease.     

Effect of Wegener's granulomatosis on work disability,need for medical care,and quality of life in patients younger than 40 years at diagnosis

OBJECTIVES: To evaluate the effects of Wegener's granulomatosis (WG) on employment status, work disability, and need for medical care of 60 consecutive WG patients aged < or = 40 years at diagnosis.METHODS: Sixty WG patients (26 male, 34 female) with a median age of 36 years (range 17-48 years) and a median duration of disease of 39 months (range 0-228 months) completed self-administered questionnaires on hospitalization, medical care, and employment status plus the Medical Outcomes Study-Short Form-36 (SF-36) estimating their health-related quality of life.RESULTS: Thirty-two of the 60 patients reported full- or part-time employment more than 3 years after diagnosis. Only 14 of the 51 patients employed at diagnosis (27%) were currently receiving a permanent work disability pension due to WG. Two additional patients had lost work because of WG. Women who were employed at diagnosis had a nearly 3-fold higher risk of losing their jobs compared with men (P = 0.0006). There were no differences with regard to age at diagnosis, disease duration, disease severity, or education level between employed and unemployed patients. Employed patients had missed a median of 14 workdays (range 0-18 days) due to WG within the past 12 months. More than half of all patients (33 of 60) had been hospitalized during the previous 12 months because of WG. Ninety-three percent of all patients had visited their physician once or more per month, more than half of them at least once per week, regardless of employment status, severity of disease, or type of current medication. Unemployed WG patients experienced significant reductions in social and physical function and in their perceived degree of general health as assessed by the SF-36.CONCLUSIONS: Twenty-seven percent of WG patients younger than age 40 who were employed at diagnosis received permanent work disability within a disease duration of 39 months. Unemployment is followed by a considerable reduction in disease-related quality of life compared with employed patients, independent of severity and extent of disease. Furthermore, because patients were followed closely by an interdisciplinary team, a high rate of hospitalization and frequent visits to physicians resulted.     

Health-related quality of life after revascularization for peripheral arterial occlusive disease: long-term follow-up

AIM: This paper reports a study to measure quality of life, before and after revascularization, in patients with intermittent claudication and critical limb ischaemia from a long-term perspective. BACKGROUND: Patients with peripheral arterial occlusive disease have a number of problems which affect their quality of life and a successful revascularization results in immediate improvements in quality of life. However, knowledge of the durability of the improvements is sparse. Therefore, research on the outcomes of treatment and nursing care should investigate the long-term effects on quality of life and daily activities. METHODS: A quasi-experimental longitudinal follow-up study was conducted with 80 patients with intermittent claudication and 62 with critical ischaemia. Assessment with the Nottingham Health Profile was made before revascularization and 6 months, 12 months and up to 4 years afterwards. The data were collected between 1995 and 2000. RESULTS: Quality of life was improved 6 and 12 months after revascularization in patients with intermittent claudication in energy, pain, emotional reactions and physical mobility, while those with critical limb ischaemia also had improvements in pain and sleep. The improvement in pain was particularly evident for both groups and remained significantly improved up to 4 years after revascularization. Patients with critical limb ischaemia, however, deteriorated significantly with regard to physical mobility between 12 months and 4 years. Being a woman and belonging to the critical ischaemia group was significantly associated with high total Nottingham Health Profile score. Thus, patients with intermittent claudication had more durable benefits from revascularization than those with critical limb ischaemia. However, both groups had less pain than at baseline after 4 years. CONCLUSION: The degree to which quality of life was durable over time seems to depend on the severity of the disease and gender. Patients with critical limb ischaemia were older, had more other diseases and a lower quality of life than patients with intermittent claudication, which confirmed that patients with critical limb ischaemia need more ongoing nursing support to maintain independence in daily life a long time after revascularization.     

Reduced colonization and infection with miconazole-rifampicin modified central venous catheters: a randomized controlled clinical trial

OBJECTIVE: Central venous catheters (CVC) are a major cause of nosocomial bloodstream infections. Catheters modified with miconazole and rifampicin that constantly and slowly release antimicrobial substances are assumed to be beneficial in reducing rates of colonization and catheter-related infections. DESIGN AND SETTING: Prospective controlled non-blinded randomized clinical trial in two German university hospitals. PATIENTS: 223 adult inpatients with CVC between October 2000 and February 2002. Baseline characteristics, APACHE II score and therapeutic interventions were comparable. INTERVENTION: Randomization to receive either a miconazole and rifampicin modified catheter (n=118) or a standard triple-lumen CVC (n=105). MEASUREMENTS, DEFINITIONS: Microbiological evaluation was done after CVC removal. A catheter was considered colonized if growth of > or =15 cfu was found by semi-quantitative roll-plate technique from a proximal or distal catheter segment. A catheter-related infection (CRI) was defined as a colonized catheter with local signs of inflammation. A catheter-related bloodstream infection (CR-BSI) was defined as a colonized catheter with isolation of the same organism from the patient's blood with accompanying clinical signs of infection. RESULTS: A colonization of CVC was observed in six patients (5.1%) with a modified catheter and 38 patients (36.2%) with a standard catheter (P < 0.001). Five patients in the modified group (4.2%) and 18 in the standard group (17.1%) developed CRI (P=0.002). One assumed CR-BSI was detected in the standard group, with none in the modified group. No adverse effects related to the modified catheters and no antimicrobial resistance were observed. CONCLUSION: CVC supersaturated with miconazole and rifampicin were associated with a significantly lower risk for catheter colonization and catheter-related infections compared to standard catheters.     

Symptomatic hand osteoarthritis in the United States: prevalence and functional impairment estimates from the third U.S. National Health and Nutrition Examination Survey, 1991-1994

OBJECTIVE: To estimate the United States prevalence of symptomatic hand osteoarthritis using American College of Rheumatology (ACR) physical examination criteria. DESIGN: The Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative cross-sectional health examination survey, performed upper-extremity physical examinations on a sample of United States adults age 60+ yrs. Data for demographics, pain history, analgesic use, and activity limitations were obtained by interview. RESULTS: Among United States adults, 58% had Heberden's nodes, 29.9% had Bouchard's nodes, and 18.2% had first carpal-metacarpal deformities. Women had significantly more first carpal-metacarpal deformities (24.3%) than men (10.3%). Symptomatic osteoarthritis prevalence at these sites was 5.4, 4.7, and 1.9%, respectively. Overall, symptomatic hand osteoarthritis prevalence by ACR criteria was 8% (95% CI 6.5-9.5%), or 2.9 million persons. Symptomatic hand osteoarthritis significantly increased with age and was decreased among non-Hispanic blacks, but there were no gender differences. Symptomatic hand osteoarthritis was associated with self-reported difficulty lifting 10 lbs (OR 2.31; 95% CI 1.23-4.33), dressing (OR 3.77; 95% CI 1.99-7.13), and eating (OR 3.44; 95% CI 1.76-6.73). Frequent monthly use was significantly increased for analgesics, especially acetaminophen, but not nonsteroidal antiinflammatory drugs. CONCLUSION: Symptomatic hand osteoarthritis affects 1 in 12 older United States adults. NHANES III data provide a population-based assessment of the impact and associated functional impairments of symptomatic hand osteoarthritis.     

Comfort and stability of wheelchair backrests according to the TAWC (tool for assessing wheelchair discomfort)

Purpose: The goal of this study was thus to determine if people with different types of wheelchair backrests on their personal wheelchairs reported different levels of comfort as measured by the Tool for Assessing Wheelchair disComfort (TAWC). Methods: Participants were between 18 and 80 years of age and were manual wheelchair users. The TAWC was used to assess the participants’ wheelchair seating discomfort levels with the wheelchair and seating systems. Results: We surveyed 131 wheelchair users to assess the comfort of their backrests on their personal wheelchairs and found a trend suggesting that rigid backrests are were less comfortable as compared with sling backrests. This finding was statistically significant in a subgroup of participants with tetraplegia. Conclusions: Although many clinicians expect rigid backrests to be more comfortable because they may provide more support, the higher discomfort ratings among rigid backrest users with tetraplegia may be due to sub-optimal shape, fit, adjustment or user preferences.

• Implications for Rehabilitation

• Development of a measure for long-term seating discomfort is needed.

• Design and development of better rigid backrests that are functional but provide adequate comfort are in need.