The data project: a shared approach between stakeholders of the healthcare system in definition of a therapeutic algorithm for inflammatory arthritis.

Rheumatic musculoskeletal diseases or RMD [rheumatoid arthritis (RA) and spondyloarthritis (SpA)] are systemic inflammatory diseases for which there are no biomarkers capable of predicting treatments with a higher likelihood of response in naive patients. In addition, the expiration of the anti-TNF blocking drugs' patents has resulted in the availability of anti-TNF biosimilar drugs with the same efficacy and safety than originators but at significantly reduced prices. To guarantee a personalized therapeutic approach to RMD treatment, a board of rheumatologists and stakeholders from the Campania region, Italy, developed a clinically applicable arthritis therapeutic algorithm to guide rheumatologists (DATA project). The general methodology relied on a Delphi technique forecast to produce a set of statements that summarized the experts' consensus. Selected clinical scenarios were discussed in light of the available evidence, and there were two rounds of voting on the therapeutic approaches. Separate discussions were held regarding rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The decision-making factors for each disease were clinical presentation, demographics, and comorbidities. In this paper, we describe a virtuous process between rheumatologists and healthcare system stakeholders that resulted in the development of a shared therapeutic algorithm for RMD patients naive to bDMARDs.

Accelerated bone turnover identifies hemiplegic patients at higher risk of demineralization.

Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications.

The psoriatic arthritis cost evaluation study: a cost-of-illness study on tumour necrosis factor inhibitors in psoriatic arthritis patients with inadequate response to conventional therapy.

OBJECTIVE: To evaluate costs, benefits and cost-effectiveness of anti-TNF agents in PsA patients with inadequate response to conventional treatment. METHODS: A total of 107 patients, from nine Italian rheumatology centres, with different forms of PsA were given anti-TNF treatment, mainly etanercept (87%). Information on resource use, health-related quality of life, disease activity, function and laboratory values were collected at baseline and through out the 12 months of therapy. Cost (expressed in euro 2007) and utility (measured by EuroQol) before and after anti-TNF therapy initiation were compared in order to estimate the incremental cost per quality-adjusted life year (QALY) gained, and cost-effectiveness acceptability curve was calculated. RESULTS: At the end of 12 months, there was a significant increase in direct cost due to an increase of drug cost caused by TNF inhibitors that was only partially offset by the decrease in indirect cost. In the last 6 months of therapy, the direct cost increased by euro5052, the cost for the National Health System (NHS) by euro5044 and the social cost by euro4638. However, a gain of 0.12 QALY resulted in a cost per QALY gained of euro40 876 for the NHS and of euro37 591 for the society. The acceptability curve showed that there would be a 97% likelihood that anti-TNF therapy would be considered cost-effective at willingness-to-pay threshold of euro60 000 per QALY gained. CONCLUSION: Cost-effectiveness ratios are within the commonly accepted willingness-to-pay threshold. These results need to be confirmed in larger samples of patients.

[The rehabilitative approach in rheumatoid arthritis]. / L'approccio riabilitativo nell'artrite reumatoide.

The rehabilitative approach for the patient with rheumatoid arthritis should be early, global and complementary to an early pharmacological therapy, in the context of a multidisciplinary approach, that should include physicians with different specialties and other health professionals. Evaluation scales assessing disability and quality of life are necessary for the rehabilitative approach. These can be classified in 2 groups: specific tools and generic tools, each evaluating different components of the health status. After the evaluation and the definition of the aims of the rehabilitation, a rehabilitative project, potentially including physical therapies, therapeutic exercises, occupational therapy and orthosis should be defined.

Validity and reliability of an Italian version of the revised Leeds disability questionnaire for patients with ankylosing spondylitis.

OBJECTIVE: The purpose of the present study was to produce an Italian version of the Revised Leeds Disability Questionnaire (LDQ) in a group of patients with ankylosing spondylitis, and to examine the psychometric properties of this version, evaluating its internal consistency, external validity and reliability. METHODS: The LDQ was administered to 60 Caucasian patients affected by ankylosing spondylitis (50 males, 10 females, mean age 46.1 +/- 14.2 yr, range 22-74, median disease duration 4.5 yr, range 1-24) together with the Italian version of the Stanford Health Assessment Questionnaire (HAQ), and anthropometric measurements. Thirty patients completed the questionnaire after a 10-day interval. Internal consistency was evaluated with Cronbach's alpha coefficient of reliability. Construct validity of the LDQ was evaluated using the correlation between the HAQ and anthropometric measurements. Test-retest reliability was assessed with the intraclass correlation coefficient. RESULTS: All patients completed the validation study. The questionnaire was internally consistent (alpha=0.90). A significant correlation was recorded between the LDQ and the HAQ score (rho=0.841, P<0.01) and the anthropometric measurements. Test-retest reliability showed a good correlation coefficient (intraclass correlation=0.97). CONCLUSION: The Italian LDQ is a valid and reliable instrument for detecting and measuring functional disability in patients with ankylosing spondylitis. Our results confirm the utility of this questionnaire as a valid and feasible functional measure for patients with ankylosing spondylitis.

Intervertebral disc lesions in diffuse idiopathic skeletal hyperostosis (DISH).

OBJECTIVE: In order to evaluate the relationships between DISH and vertebral osteochondrosis (degenerative disc disease), the radiographs of the spine of 69 DISH patients were compared to those of 68 controls. METHODS: Radiographs of 69 patients affected by DISH according to Resnick's criteria and of 68 control subjects affected by diseases other than DISH, were evaluated in order to determine the prevalence of vertebral osteochondrosis, diagnosed by the occurrence of moderate to severe reduction in the intervertebral disc height and of the extensive radiographic changes typical of degenerative disc disease, including vacuum phenomena and vertebral body marginal sclerosis. The rate ratios with 95% confidence intervals were computed, with stratification by age groups. RESULTS: Thirty-eight DISH patients (55.1%) and 34 controls (50%) showed vertebral osteochondrosis. Stratification by age revealed an increased prevalence of vertebral osteochondrosis in younger DISH patients with respect to controls (p < 0.05). CONCLUSION: Our results show that vertebral osteochondrosis may be associated with DISH and underline the differences between classification and diagnostic criteria. Moreover, it could be hypothesized that DISH plays a predisposing role in the development of vertebral osteochondrosis during the early stages of the disease, causing an early modification in the physiological curves of the spine.

Subclinical peripheral nerve involvement in patients with rheumatoid arthritis.

OBJECTIVE: Clinical involvement of the peripheral nervous system is uncommon in rheumatoid arthritis (RA); the most common disorders are multiple mononeuritis, sensorimotor neuropathy, and entrapment neuropathy. This study was undertaken to investigate the occurrence of electrophysiologically evident peripheral nerve involvement in RA patients without a clinical history of peripheral nerve involvement. METHODS: Forty RA patients were examined neurologically and electrophysiologically, and sural nerve biopsies were performed in 4. RESULTS: No patient reported symptoms or signs of peripheral nerve involvement. Twenty-six patients (65%) exhibited electrophysiologic findings consistent with a sensorimotor neuropathy (in 2 of them a carpal tunnel syndrome was also present), while 3 patients showed isolated carpal tunnel syndrome. There was a moderate loss of myelinated fibers in 3 of the 4 nerve biopsy samples, and all showed an increased number of endo- and perineurial vessels and some signs of axonal degeneration. CONCLUSION: Patients with RA may have electrophysiologic and histologic findings of peripheral nerve damage, even in the absence of clinical evidence of peripheral nerve involvement.

Diffuse idiopathic skeletal hyperostosis (DISH): a retrospective analysis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a skeletal disease characterized by ligamentous ossification of the anterolateral side of the spine. The radiographs of the spine of 69 patients (22 males, 47 females, mean age 64.97 +/- 8.83 years) affected by DISH according to Resnick's criteria were selected. A lower rate of lumbar spine involvement (71%) and a different distribution between sexes were demonstrated, as compared to the data from the literature. Data on relationships among extent of hyperostosis, occupation and metabolic disorders suggest that an important role might be played by the exposure to microtrauma, while, in subjects affected by a metabolic disorder, this condition would represent a prevalent pathogenetic factor. These data underline some peculiarities in the clinical picture of DISH in the population from Campania, that could depend on genetic factors.

Determinants of bone mineral density in immobilization: a study on hemiplegic patients.

Osteoporosis that develops during immobilization is a severe condition that confers increased risk of fractures with their burden of mortality and disability. The aim of this study was to investigate the determinants of immobilization osteoporosis. As a model of this condition we studied hemiplegic subjects, measuring bone mineral density in the paralyzed lower limb as compared with the non-paralyzed one. In spite of the limits related to the loss of nervous stimulation, this model offers the advantage of a proper control for the complex genetic and environmental cofactors involved. We examined 48 hemiplegic subjects (31 men, 17 women in menopause) admitted consecutively over a 9-month period. Mean length immobilization was 10.9 months for men (range 1-48 months) and 7.8 months for women (range 1-40 months). The average time since menopause was 14.9 years (range 1.7-23.9 years). For each subject the following were performed: questionnaire, medical examination, anthropometric measurements, evaluation of the scores for spasticity and for lower limb motor capacity in order to account for the different degrees of disability among patients. Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA) at both femoral necks. For each patient we defined a percentage difference in bone loss between the paralyzed and non-paralyzed limb. Regression coefficient were calculated by multiple logistic regression. There was significant bone loss in the paralyzed limb in both sexes, accounting for up to 6.3% in women. Multiple regression analysis showed that the degree of bone loss depends significantly and directly on the length of immobilization, even when controlling for age and sex in the regression model (R = 0.193, p = 0.034). However, when time since menopause was included in the regression model, with length of immobility as a covariate, it was the only significant determinant of bone loss (R = 0.312, p = 0.039). No additional factors were observed among men. No differences were shown with regard to anthropometric measurements or functional scores. Length of immobilization accounts only for a small fraction of bone loss, which does not exceed 5% of the total variance. Our data show that postmenopausal women should be considered at highest risk for osteoporosis in cases of immobility and that different factors, other than length of immobility, might come into play in determining bone loss in this condition.

[The determinants of bone mineral density in hemiplegic patients. Preliminary data]. / Determinanti della densità minerale ossea in pazienti emiplegici. Dati preliminari.

We studied a group of hemiplegic patients to determine the amount of bone loss of the paretic versus the normal limb and to evaluate the importance of several variables in determining this difference. Thirty consecutive subjects with hemiplegia caused by a cerebral vascular accident were studied: 15 postmenopausal women (average age 65.1 years) and 15 men (average age 58.3 years) (average age of entire group, 63.2 years; age range of entire group, 27-84 years). The mean duration of immobilization was 7.7 months for women (range 1-40 months) and 10.5 months for men (range 1-48 months). All subjects had a complete physical examination, underwent bilateral femoral neck DEXA, and filled out a questionnaire. The percent difference (delta) between the paretic and normal limb was 6.1% in the women and 3.8% in the men. Logistic regression analysis, after control for age and sex, indicated that the degree of demineralization depended significantly and directly on the duration of immobilization and depended inversely on the time elapsed since menopause. Our data evidence the importance of immobilization osteoporosis and point to the role of hormonal factors in its pathogenesis.

Ossification of the posterior longitudinal ligament in one of a pair of identical twins concordant for ankylosing spondylitis.

A pair of identical twins suffering from ankylosing spondylitis is reported. One brother developed an earlier-onset disease and showed ossification of the posterior longitudinal ligament and the flavum ligament in his cervical spine.

POEMS syndrome: follow-up study of a case.

We report here the case of a 20-year-old man with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M proteins, skin changes). This rare syndrome followed a 3-year history of a syndrome that mimics a chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment with cyclophosphamide induced regression of the syndrome and improved peripheral nerve conduction.

The use of a modified tonometer in burn scar therapy.

We report on the use of a modified Schiotz tonometer to evaluate the effects of therapies on burn scars. It is now possible to quantify the course of cicatrization with tonometry. Because tonometry affords a precise evaluation of burn scar diagnosis and prognosis, it is possible to avoid arbitrary clinical evaluation of the burn scarring process.