Concordance of the SHEA-IDSA severity classification for Clostridium difficile infection and the ATLAS bedside scoring system in hospitalized adult patients.

PURPOSE: The Society for Healthcare Epidemiology of America and Infectious Diseases Society of America (SHEA-IDSA) guidelines for the treatment of Clostridium difficile infection (CDI) recommend initial treatment of CDI based on disease severity. This severity definition has not been validated or evaluated based on clinical outcomes. The ATLAS scoring system is a validated tool useful in predicting treatment response and mortality in CDI. The main purpose of this study is to evaluate the concordance of the ATLAS scoring system and the SHEA-IDSA staging for CDI severity. METHODS: This was a retrospective study which included hospitalized patients with confirmed CDI. Bivariate analyses compared baseline demographics and clinical information between patients with nonsevere and severe CDI based on the SHEA-IDSA criteria for CDI severity. Kappa scores were calculated to compare the concordance of the two scoring systems in defining CDI severity. Sensitivity and specificity of the ATLAS scoring system to determine CDI severity were calculated using the SHEA-IDSA criteria as the reference standard. RESULTS: Sixty-four patients met inclusion criteria. Of those, 62.5% were classified as mild to moderate CDI, 25% were severe, uncomplicated, and 12.5% were severe, complicated based on SHEA-IDSA criteria. In the bivariate analyses, ATLAS score breakpoints of ≥ 4, ≥ 5, and ≥ 6 revealed moderate agreement with the SHEA-IDSA classification for severity. The sensitivities and specificities for ATLAS scores in predicting CDI severity ranged from 58.3 to 87.5, and 67.5-87.5%, respectively. CONCLUSION: The ATLAS score may be useful in evaluating CDI severity and determining drug therapy selection.

The Sjögren's Syndrome Damage Index--a damage index for use in clinical trials and observational studies in primary Sjögren's syndrome.

OBJECTIVE: To validate a tool for assessment of accumulated damage in patients with Primary SS (PSS). METHODS: Of the total 114 patients fulfilling American-European Consensus Group (AECG) criteria for PSS 104 were included in the study and assessed by rheumatologists at T (time) = 0 months and T = 12 months. On each occasion, damage and activity data, and autoantibody status were collected. SF-36 and Profile of Fatigue and Discomfort-Sicca Symptoms Inventory (PROFAD-SSI) questionnaires were completed. Cross-sectional analysis of this data was subject to a process of expert validation by 11 ophthalmologists, 14 oral medicine specialists and 8 rheumatologists. Items were removed from the index if >or= 50% of respondents recommended exclusion. Statistical validation was performed on remaining items. Spearman's rank analysis was used to investigate associations between damage scores and other disease status measures and Wilcoxon matched-pair analysis to assess sensitivity to change in the damage score. RESULTS: Based on the expert validation, a 29-item damage score was agreed incorporating ocular, oral and systemic domains. Total damage score correlated with disease duration at study entry (r = 0.436; P < 0.001), physical function as measured by SF-36 (r = 0.250, T = 0 months; r = 0.261 T = 12 months) and activity as measured by the Sjögren's Systemic Clinical Activity Index (r = 0.213, T = 0 months; r = 0.215, T =12 months). Ocular damage score correlated with the 'eye dry' domain of PROFAD-SSI (r = 0.228, T = 0 months; r = 0.365, T = 12 months). Other associations not present on both assessments were considered clinically insignificant. On Wilcoxon analysis, the index was sensitive to change over 12 months (z = -3.262; P < 0.01). CONCLUSION: This study begins validation of a tool for collection of longitudinal damage data in PSS. We recommend further trial in both the experimental and clinical environment.

Sjögren's Systemic Clinical Activity Index (SCAI)--a systemic disease activity measure for use in clinical trials in primary Sjögren's syndrome.

OBJECTIVE: This article describes the development of the Sjögren's Systemic Clinical Activity Index (SCAI) for the measurement of systemic disease activity in patients with primary Sjögren's syndrome (PSS). METHODS: A pilot tool was developed based on expert consensus and previous published data. One hundred and four patients with PSS were evaluated in a cross-sectional analysis, of whom 65 were reviewed at 3-monthly intervals, using this index, over a 12-month period. Factor analysis was used to evaluate the proposed domain structure. External validation was assessed by comparison with relevant domains of the Profile of Fatigue and Discomfort (PROFAD), Medical Outcomes Study Short Form-36 (SF-36) and The World Health Organization Quality of Life-Bref (WHOQOL-BREF). Sensitivity to change was assessed by comparing SCAI-derived flares with physician-designated disease flare and intention-to-treat analysis. A reliability and repeatability workshop was also held. RESULTS: Factor analysis supported the proposed domain structure. There were strong correlations between the SCAI fatigue, musculoskeletal and Raynaud's components and the PROFAD fatigue, arthralgia and vascular domains. There was a significant correlation between change in therapy and SCAI-defined flares (P = 0.01). The mean kappa-test results both for reliability of the SCAI and for physician repeatability were 0.71. CONCLUSION: This initial evaluation supports the potential for the SCAI as a tool for systemic activity assessment in patients with PSS but additional work is required to assess sensitivity to change in clinical therapeutic trials.

Lymphedema of the upper limb in patients with psoriatic arthritis.

Upper limb lymphedema occurs rarely in rheumatoid arthritis (RA) but has been reported only once in psoriatic arthritis (PsA). The pathogenesis is unknown. This study describes four patients (three women) with upper limb lymphedema, chronic symmetrical polyarthritis, and psoriasis. Three were seronegative, diagnosed PsA; one was seropositive. Age ranged from 39 to 64 years, duration of psoriasis was 6 to 42 years, and duration of arthritis was 6 to 12 years. Onset of lymphedema was unrelated to the extent or severity of arthritis, and no other cause for this condition was identified. Radiological appearances ranged from mildly abnormal to advanced joint destruction, but carpal disease was prominent in all patients. Lymphoscintigraphy was abnormal in three subjects. Lymphedema became bilateral in two and was associated with radiological progression of arthritis. Disease-modifying therapy produced improvement of lymphedema in two patients and correction of the lymphoscintigraphic abnormality in one. This study describes upper limb lymphedema in patients with PsA and suggests that local synovitis may play a role in its pathogenesis.

Adhesion molecules in untreated inflammatory arthritis: synovial expression and levels in synovial fluid and serum [corrected].

Adhesion molecules play a critical role in regulating leucocyte migration at sites of inflammation. The relationship of soluble forms in serum or synovial fluid (SF) to synovial membrane expression in inflammatory arthritis is controversial. We examined soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin levels in matched serum and SF, and their relationship to expression in synovium obtained at the same time in 13 patients with previously untreated inflammatory arthritis. Serum-soluble (s)ICAM-1 correlated with sedimentation rate (T = 0.45), Ritchie articular index (T = 0.47) and SF sICAM-1 (T = 0.48), and SF sICAM-1 correlated with membrane ICAM-1 expression (p < 0.02). sE-selectin and sVCAM-1 levels were unrelated to disease activity or membrane expression. Membrane E-selectin expression correlated inversely with ICAM-1 expression (T = -0.57) and serum sICAM-1 (T = -0.54). Serum sE-selectin correlated inversely with membrane ICAM-1 expression (T = -0.55). The correlations observed between ICAM-1 in serum, SF, synovium and disease activity suggest that ICAM-1 could be a useful target for immunotherapy. The inverse relationship of ICAM-1 and E-selectin suggest important differences in regulation and pathogenetic roles.

Skin reactivity to atypical mycobacteria in cystic fibrosis.

Atypical mycobacterial disease has been described in a small number of patients with cystic fibrosis. Apart from one uncontrolled study, there is little information regarding atypical mycobacterial skin reactivity in this group of patients. We evaluated delayed cutaneous hypersensitivity to purified extracts of Mycobacterium avium, Mycobacterium intracellular, Mycobacterium kansasii and Mycobacterium bovis in 23 healthy controls and 43 adult and adolescent patients with cystic fibrosis. Fifteen of the cystic fibrosis group were receiving regular corticosteroids. Additionally, direct smear examination and Lowenstein Jensen culture were performed on sputum from the cystic fibrosis group. The prevalence of positive skin reactions was similar in the group with cystic fibrosis (30%) and in the control group (57%). Subgroup analysis showed that those cystic fibrosis patients receiving corticosteroids had a markedly lower prevalence of positive reactions (7%) compared to controls (P less than 0.01). When this subgroup was excluded from analysis, the prevalence of positive skin reactions among patients with cystic fibrosis was 43%. In the prospective sputum bacteriology study, one of the 43 cases grew Mycobacterium avium-intracellulare and had clinical and radiological evidence of this disease. Of note, this patient showed positive skin tests to all four mycobacterial species tested. Our data show no difference in the prevalence rate of positive skin reactions to atypical mycobacterial antigens between a control population and an adult cystic fibrosis population. In addition, the predictive value of skin testing is low in cystic fibrosis due to the high prevalence of cross-reactivity between different mycobacterial species and the high prevalence of anergy among those patients with advanced disease receiving treatment with corticosteroids.

Assessment of cognitive function in patients with systemic lupus erythematosus.

The spectrum of central nervous system manifestations of systemic lupus erythematosus (SLE) is very broad and has been found to include subtle subclinical cognitive dysfunction which may be detected only by the lengthy process of detailed neuropsychological evaluation. This study reports the value of estimating premorbid intelligence as a simple yet effective means of screening for subclinical cognitive dysfunction. Twenty one female patients with clinically quiescent SLE underwent neuropsychological examination at entry to the study. In all patients, this examination included measurement of full-scale intelligence quotient (IQ), verbal and performance IQ as well as verbal and visual memories. In addition, premorbid intelligence was estimated using the Schonell graded word reading test. Nine patients (43%) gave a history of neuropsychiatric (NP) disease. No difference was identified between the results of the neuropsychological evaluation in these 9 patients and in either the other SLE patients or in age and sex matched control patients. Sixteen patients were re-evaluated 1 year later. A comparison of measured full-scale IQ with the estimated premorbid intelligence identified a subgroup of 3 patients who demonstrated a significant reduction in intelligence. Unlike the other 13 patients, these 3 patients had multiple (3 or more) other features of cognitive impairment.

Aminoglycoside induced ototoxicity in patients with cystic fibrosis.

The improved survival of cystic fibrosis (CF) patients is partly due to intensive treatment for their chronic infections. Treatment usually includes intravenous and nebulised aminoglycoside antibiotics and they receive a large cumulative dose of these antibiotics over their lifetime. There is little information in the literature on the prevalence of ototoxicity due to aminoglycoside in these patients. We performed pure tone audiometry on 43 CF patients aged 14-42 years. Seven (16%) had bilateral sensorineural hearing loss (SNHL) for high frequency sounds, consistent with aminoglycoside induced ototoxicity. However, only 2 of these patients had documented toxic serum levels in the past. The identification of bilateral SNHL in one in six adult CF patients is a cause for concern. It may be that the high cumulative dose of aminoglycosides received by these patients may be causing inner ear injury in the absence of specific episodes of toxic serum levels.

Pseudomonas colonization in cystic fibrosis: lack of correlation with secretion of ABO blood group antigens.

In cystic fibrosis, a majority of patients develop persistent lifelong respiratory tract colonisation with pseudomonas aeruginosa while a minority do not appear to become colonised. There is some evidence that non-secretion of ABO Blood Group antigens into body secretions is a marker for susceptibility to certain gram negative infections. Therefore, we studied 47 adult patients with cystic fibrosis to identify an association, if any, between secretor status and the presence or absence of pseudomonas aeruginosa in their sputum. Overall, we found no difference between the prevalence of non-secretors in our patient group and in the normal population. Furthermore, there was no association between secretor status and presence or absence of pseudomonas aeruginosa in sputum. We conclude that secretor status is unlikely to play a major role in susceptibility to pseudomonas aeruginosa infection in patients with cystic fibrosis.

High resolution computed tomography in cystic fibrosis: correlation with pulmonary function and assessment of prognostic value.

OBJECTIVE: To assess the correlation between HRCT and pulmonary function in patients with CF. Further, to assess the prognostic value of HRCT in these patients. SUBJECTS AND METHODS: Clinical examination, chest radiographs and HRCT scans on 30 CF patients with an average age of 17 were scored using established scoring systems. The results were correlated with FEV1 and FVC both at time of CT scanning and after 30 months. Results were also correlated with the clinical progress of the patients over the follow-up period. RESULTS: HRCT, chest radiograph and clinical examination demonstrated similar correlation (p < 0.001) with FEV1 and FVC at the time of scanning. HRCT demonstrated the closest correlation with the clinical progress of the patients over the follow-up period and with follow-up pulmonary function. A maximum combined score for bronchiectasis and emphysema on HRCT seemed to indicate a poor prognosis. CONCLUSION: HRCT in CF patients correlates well with pulmonary function at time of scanning and at follow-up, and with clinical progress. There may be a role for CT in the identification of adolescent/adult patients who can be expected to need aggressive therapy in the future.

Cystic fibrosis in adolescents and adults.

A cystic fibrosis (CF) clinic for adults was established in 1977. We have reviewed the data on 164 patients who attended between 1977 and 1989. Twenty four patients had died, 11 being over 20 years of age at the time of death. Of the 140 patients still alive, 61% were male and 53% were aged over 20 years. Only 55% were diagnosed by one year and 88% by ten years. Almost all patients had respiratory symptoms and sputum culture yielded pseudomonas species in 69%. Other respiratory problems included major haemoptysis and pneumothorax, each in 10%. We found a wide range of respiratory impairment among older patients. Among 33 patients aged over 23 years, the mean (+/-S.D.) percent predicted FEV1 and FVC were 53.3% (+/- 18%) and 71.4 (+/- 20%) respectively. Mean weight in this group was 92.5% (+/- 14) of predicted. Malabsorption occurred in most patients and meconium ileus equivalent occurred in 34%. Other complications were clinical hepatomegaly (16%), diabetes mellitus (9%) and arthropathy (20%). Most patients were taking continuous antibiotics by mouth (89%) and by nebuliser (48%), beta-2 agonists by inhaler (57%) and oral steroids (29%). Almost all were taking multivitamins, pancreatic replacement therapy and multiple nutritional supplements. The number of CF "bed days" grew 12 fold since 1979 and the mean stay in hospital was double the hospital mean. The economic impact was such that over 1/4 of the annual hospital antibiotic budget was expended on CF patients.

Cystic fibrosis in adolescents and adults.

A cystic fibrosis (CF) clinic for adults was established in 1977. We have reviewed the data on 164 patients who attended between 1977 and 1989. Twenty four patients had died, 11 being over 20 years after time of death. Of the 140 patients still alive, 61% were male and 53% were aged over 20 years. Only 55% were diagnosed by 1 year and 88% by 10 years. Almost all patients had respiratory symptoms and sputum culture yielded Pseudomonas species in 69%. Other respiratory problems included major haemoptysis and pneumothorax, each in 10%. We found a wide range of respiratory impairment among older patients. Among 3 patients aged over 23 years the mean (+/- S.D.) percent predicted FEV1 and FVC were 53.3% (+/- 18%) and 71.4% (+/- 20%) respectively. Mean weight in this group was 92.5% (+/- 14) of predicted. Malabsorption occurred in most patients and meconium ileus equivalent occurred in most patients and meconium ileus equivalent occurred in 34%. Other complications were clinical hepatomegaly (16%), diabetes mellitus (9%) and arthropathy (20%). Most patients were taking continuous antibiotics by mouth (89%) and by nebuliser (48%), beta-2 agonists by inhaler (57%) and oral steroids (29%). Almost all were taking multivitamins, pancreatic replacement therapy and multiple nutritional supplements. The number of CF "bed days" grew 12 fold since 1979 and the mean stay in hospital was double the hospital mean. The economic impact was such that over 1/4 of the annual hospital antibiotic budget was expended on CF patients.

Efficacy of tibial nerve block, local steroid injection or both in the treatment of plantar heel pain syndrome.

BACKGROUND: Plantar Heel Pain Syndrome (PHPS) describes centralised plantar heel pain and tenderness. It can account for up to 15% of referrals to clinicians involved in the treatment of foot pain. OBJECTIVE: To compare tibial nerve block, local infiltration with steroid or both combined in the treatment of PHPS. METHODS: Patients with PHPS were randomly assigned to three treatment groups: Group 1-steroid injection to heel; Group 2-local anaesthetic block to tibial nerve; Group 3-both procedures. Pain visual analogue scale (VAS) was measured at baseline and after 1, 6 and 26 weeks. Heel tenderness index (HTI) was measured at baseline and after 6 weeks. The patient rated their discomfort from the injection(s) using a VAS. RESULTS: Forty-five patients (27 female) were recruited, 14 in Group 1, 12 in Group 2 and 19 in Group 3. Median age was 55, disease duration was 10 months and baseline pain VAS was 7.0 cm. All groups experienced a sustained improvement in pain VAS between baseline and weeks 1, 6 and 26 (all p<0.0001). Group 1 reported significantly lower pain VAS that those in Group 2 (p<0.01) or Group 3 (p<0.05) at week 6. Group 2 found the procedure less uncomfortable than Group 1 (p<0.01). The HTI was significantly higher in Group 2 at 6 weeks compared to Group 1 (p<0.005) and Group 3 (p<0.05). CONCLUSIONS: This study suggests that the natural history of PHPS following an injection is encouraging, that a tibial nerve block reduces the discomfort of the procedure, that a steroid injection to the heel may accelerate improvement and that clinicians should consider a combination of both strategies.

The influence of medication beliefs and other psychosocial factors on early discontinuation of disease-modifying anti-rheumatic drugs.

OBJECTIVE: Although drug survival time might be a better measure of clinical effectiveness than drug adherence, there is little research literature in this area, in particular about the influence of medication beliefs and psychosocial factors. This study aimed to investigate the above relationships using patients who were newly diagnosed with rheumatoid arthritis (RA). METHODS: Sixty-eight RA patients starting their first disease-modifying anti-rheumatic drug (DMARD) were interviewed shortly after initiating therapy, and then one year later. Before each meeting, patients were asked to complete a set of questionnaires, including Beliefs about Medication, Spielberger State-Trait Anxiety Inventory - Short Form, the modified Stanford Health Assessment Questionnaire, Beck Depression Inventory-1 and the Significant Others Scale. Relevant sociodemographic background, disease activity and drug history were obtained. Clinical measures such as grip strength and joint count were assessed. RESULTS: A stepwise logistic regression analysis was applied to two patient groups: those who continued taking their DMARD one year later, and those who did not. No significant difference between the groups for levels of disability and disease activity were found. Only age and anxiety emerged as significant predictors of drug discontinuation at 52 weeks. CONCLUSIONS: Contrary to expectation, this study demonstrated that older and less anxious patients were more likely to discontinue taking their initial DMARD within the first year. The study may have implications for counselling older and less anxious patients prior to DMARD therapy. However, there are limitations in generalizing the results because of the small population sample. It also did not take into account drug intolerance as a pertinent factor for early drug discontinuation.

Is pre-assessment for anti-TNF therapy in RA necessary in the UK? Analysis of DAS28 in six centres.

OBJECTIVES: National Institute for Health and Clinical Excellence (NICE) guidelines for anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA) state that two pre-assessments of Disease Activity Score (DAS28) should be performed a month apart. We performed a retrospective audit of data from six centres to determine the stability of DAS28 between assessments, and the proportion of patients still satisfying eligibility criteria at baseline. METHODS: All RA patients assessed for anti-TNF from six centres had their pre-assessment DAS28 (DAS-1) compared with their baseline DAS28 (DAS0) using paired t-tests, and a similar analysis for the components of the DAS28. Patients who were no longer eligible for anti-TNF at DAS0 were noted. RESULTS: Six hundred and seventy-nine RA patients showed no significant change in the DAS28, with a mean DAS-1 of 6.74 and DAS0 of 6.73. (P = 0.86). Of the patients, 97.2% fulfilled the UK eligibility criteria at DAS0. Comparison of the individual components of the DAS28 between the two pre-assessment dates showed that there was no significant difference between either the numbers of swollen joints or the erythrocyte sedimentation rate (ESR), but there was a significant increase in the numbers of tender joints of 1.41 (P < 0.001) and in the visual analogue scale (VAS) of 4.22 (P < 0.001). DISCUSSION: The overwhelming majority of patients who fulfil eligibility criteria for anti-TNF drugs 1 month prior to baseline also fulfil the criteria at baseline. There is no significant change in the DAS28 over the month waiting to go onto anti-TNF therapy. A single assessment of the DAS28 would suffice to enable patients to go on to anti-TNF treatment.

The overall status in rheumatoid arthritis (OSRA) measure--further evidence to support its use in clinical practice.

OBJECTIVES: The overall status in rheumatoid arthritis (OSRA) instrument is a simple summary of health status, including disease activity (OSRA-A) and damage (OSRA-D) scores. Despite evidence of the validity of the OSRA, uptake has been low. This study aimed to assess the responsiveness and re-examine the validity of the OSRA using the measures from the British Rheumatoid Outcome Study Group (BROSG) randomized controlled trial of aggressive vs symptomatic treatment of rheumatoid arthritis (RA) patients. METHODS: 466 patients were recruited. Outcome measures included the OSRA, the OMERACT core set and the DAS28, and were collected at baseline and annually for the 3 yrs of the trial. X-rays of the hands and feet were taken at baseline and 3 yrs. Patients were assigned a Townsend score (a measure of social deprivation) according to area of residence. Construct validity was assessed by correlating the OSRA with a range of outcome measures, and testing for the known inequality in RA outcome between patients classified by social deprivation. Responsiveness to change was assessed against self-reported change over the first year of the trial. RESULTS: The OSRA-A and OSRA-D measures demonstrated construct validity, performing as hypothesized. The OSRA-A was the most responsive measure in the BROSG trial in detecting patient reported improvement and deterioration. The OSRA-D demonstrated similar responsiveness to alternative measures. CONCLUSIONS: Our results demonstrate the validity and responsiveness of the OSRA, and its potential for inclusion in clinical trials. More important, as the OSRA is quick and easily calculated, uses routinely collected information, and provides useful quantitative information about a patient's status and progress it is suitable for use in the routine clinic.