Combined manual and automated immunophenotypisation identified disease-specific peripheral blood immune subpopulations in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.

OBJECTIVES: Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are associated with abnormal immune cell functions. We combined manual and automated profiling in subpopulations of T-cells, B-cells and monocytes, in parallel to functional testing and clinical correlation. METHODS: Using flow cytometry, we analysed the expression of CCR4, CCR6 and CXCR5 on helper and cyotoxic T-cells, CD32B and CD86 on naïve and memory B-cells, and CCR1, CCR2, CCR4 and CXCR4 on monocytes in chronic high-disease activity patients to identify peripheral blood subpopulations. Cell activation, proliferative capability and osteoclastogenic effects were tested in vitro. Comparison with synovial compartment, clinical data and anti-TNF treatment were added to peripheral blood analysis. RESULTS: PsA had lower double-negative T-cell frequency, while RA had lower double-positive T-cell frequency and expanded Th1-like and cytotoxic T-cell subsets. CD32B expression was increased on naïve and memory B-cells in AS and associated with disease activity. CCR6+ and CXCR5+ cytotoxic T-cells and CD32B+ naïve and memory B-cells were highly enriched within the synovial compartment. T-cells and B-cells from AS exhibited enhanced activation and proliferation in vitro, whereas T-cell conditioned medium from RA produced an increased osteoclastogenic effect. CCR1 and CXCR4 were upregulated on osteoclastogenic monocyte subsets of RA, AS and PsA patients. Bioinformatic Citrus analysis identified additional T-cell, B-cell and monocyte clusters specifically associated with each disease. CONCLUSIONS: By combining manual and automated data analysis, our study revealed several disease-specific immune cell subpopulations, particularly cytotoxic T-cell subsets in RA and memory B-cell subsets in AS, which may serve as an indicator of active disease or possible therapeutic target.

Advanced Clinical and Radiological Features of Ankylosing Spondylitis: Relation to Gender, Onset of First Symptoms and Disease Duration.

To determine the frequency of advanced clinical and radiological features of AS with reference to gender, onset of symptoms and disease duration. Fifty-seven patients diagnosed with AS were included in this study. Functional evaluation of the musculoskeletal system detected advanced clinical features: rubber-ball phenomenon, flattening of the chest anterior wall, diastasis of rectus abdominis muscle, steel back phenomenon, umbilical extrusion, skiing posture. Conventional radiographs of sacroiliac joints, pelvis and axial skeleton were obtained in order to analyze signs of sacroiliitis, syndesmophytes, vertebral squaring and ligamentous ossification. Statistical significance is found in the distribution of particular advanced clinical and radiological features of AS between men and women: rubber-ball phenomenon (p = 0.002), flat chest (p = 0.002), diastasis of rectus abdominis muscle (p = 0.002), skiing position (p = 0.000), syndesmophytes (p = 0.009) and ligamentous ossification (p = 0.030) in thoracic and lumbar spine. Onset of first disease symptoms (> 20 years of age) is significantly associated with radiological changes in thoracic spine (ligamentous ossification, p = 0.015) and cervical spine (vertebral squaring, p = 0.032). Longer disease duration (> 10 years) is significantly associated with the appearance of particular clinical features: rubber-ball phenomenon, p < 0.01; rectus abdominis diastasis, p=0.042) and radiological changes of sacroiliac joints (grade IV sacroileitis, p = 0.012), thoracic and lumbar spine (syndesmophytes, p = 0.015; ligamentous ossification, p = 0.027). Our study shows that the occurrence of clinical and some radiological features of AS appears to be gender dependent. Furthermore, onset of first disease symptoms (> 20 years of age) and longer disease duration (> 10 years) are associated with the higher risk of developing particular clinical signs and radiological features in sacroiliac joints and axial skeleton.

Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis.

The inflammatory milieu favors recruitment and activation of osteoclasts, and leads to bone destruction as a serious complication associated with arthritis and with other inflammatory processes. The frequency and activity of osteoclast progenitors (OCPs) correspond to arthritis severity, and may be used to monitor disease progression and bone resorption, indicating the need for detailed characterization of the discrete OCP subpopulations. Collectively, current studies suggest that the most potent murine bone marrow OCP population can be identified among lymphoid negative population within the immature myeloid lineage cells, as B220(-)CD3(-)CD11b(-/lo)CD115(+)CD117(+)CX3CR1(+) and possibly also Ter119(-)CD11c(-)CD135(lo)Ly6C(+)RANK(-). In peripheral blood the OCP population bears the monocytoid phenotype B220(-)CD3(-)NK1.1(-)CD11b(+)Ly6C(hi)CD115(+)CX3CR1(+), presumably expressing RANK in committed OCPs. Much less is known about human OCPs and their regulation in arthritis, but the circulating OCP subset is, most probably, comprised among the lymphoid negative population (CD3(-)CD19(-)CD56(-)), within immature monocyte subset (CD11b(+)CD14(+)CD16(-)), expressing receptors for M-CSF and RANKL (CD115(+)RANK(+)). Our preliminary data confirmed positive association between the proportion of peripheral blood OCPs, defined as CD3(-)CD19(-)CD56(-)CD11b(+)CD14(+), and the disease activity score (DAS28) in the follow-up samples from patients with psoriatic arthritis receiving anti-TNF therapy. In addition, we reviewed cytokines and chemokines which, directly or indirectly, activate OCPs and enhance their differentiation potential, thus mediating osteoresorption. Control of the activity and migratory behaviour of OCPs as well as the identification of crucial bone/joint chemotactic mediators represent promising therapeutic targets in arthritis.

Association of systemic and intra-articular osteoclastogenic potential, pro-inflammatory mediators and disease activity with the form of inflammatory arthritis.

PURPOSE: We aimed to assess osteoclastogenic potential of peripheral blood mononuclear cells (PBMC) and synovial fluid-derived mononuclear cells (SFMC) in different forms of arthritis and to correlate it with inflammatory mediators within intra-articular and circulatory compartments. METHODS: Paired PBMC and SFMC samples of patients with rheumatoid arthritis (RA; n = 10) and psoriatic arthritis (PsA; n = 10), and PBMC of healthy controls were cultured to assess osteoclastogenic potential by the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) and expression of OC-related genes (receptor activator of nuclear factor-κΒ (RANK), cFMS, and TRAP). Osteoclastogenesis was correlated with the arthritis-related inflammatory indicators in serum and synovial fluid (SF). RESULTS: Number of OCs differentiated from PBMC was significantly higher in RA and PsA compared with control, with RA having more OCs compared with PsA. There was no difference in SFMC OC number between arthritic patients, but RANK expression in OCs differentiated from SFMC was higher in PsA compared with RA. SF of PsA patients more potently induced OC differentiation from control CD3(-)CD19(-)CD56(-)CD11b(+)CD115(+) PBMC compared with RA, paralleled with higher RANK-ligand expression in PsA SFMC. Positive correlations of OC number with erythrocyte sedimentation rate, serum level of CCL2, and PBMC gene expression of interleukin-18 and Fas-ligand were observed. CONCLUSION: Osteoclastogenic potential is systemically enhanced in patients with RA, paralleled by disordered systemic and local expression of proinflammatory mediators, whereas PsA involves specific deregulation in RANKL/RANK axis. Our study reveals arthritis-specific mediators associated with the form of arthritis, indicating clinical relevance for diagnosis and treatment.

Which clinical variables have the most significant correlation with quality of life evaluated by SF-36 survey in Croatian cohort of patient with ankylosing spondylitis and psoriatic arthritis?

The aim of our study was to assess clinical variables with the best correlation to quality of life (QOL) assessed by medical outcome survey Short-Form 36 (SF-36) in patients with spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). We analyzed the cohort of 54 patients (22 patients with PsA and 32 patients with AS), who filled the Croatian version of SF-36. For each type of arthritis, patients were clinically evaluated using the extensive list of clinical variables categorized into subjective and objective group. For AS patients, subjective and objective variables (spinal mobility measurements, clinical assessment of spinal pain, patient assessments of disease activity and pain) correlated mainly with the physical functioning concept of SF-36. Patients assessments of fatigue correlated with the energy/fatigue subscale, whereas patient assessment of enthesial pain correlated with the pain subscale. Correlations between clinical variables and SF-36 concepts of PsA patients showed more diverse distribution than for AS. Objective variables (spinal mobility measurements, a 76-joint score, clinical assessment of spinal pain) correlated with concepts concerning physical health and pain. Several subjective patient assessments correlated with energy/fatigue, emotional well-being, pain and general health subscales. Both patient and physician assessment of PsA activity correlated with the role limitations due to emotional problems. Bath ankylosing spondylitis functional index (BASFI) had the strongest correlation with the physical functioning concept of SF-36 in both diseases. Our findings provide important information to help selecting the variables with strongest impact on QOL, for better planning the management strategies and achieving better rehabilitation results.

Quantitative analysis of digitopalmar dermatoglyphics in fifty male psoriatic spondylitis patients.

By the quantitative dermatoglyphic analysis of digitopalmar ridge count in fifty male psoriatic spondylitis patients were researched 25 dermatoglyphics traits: number of epidermal ridges on the all ten fingers, their sum for five and ten fingers, four traits on the both palms, i.e. between a-b, b-c, c-d and a-d triradii, and atd angles and their bilateral sum in degrees. The data obtained were compared with those recorded in a control group of 200 pairs of imprints of phenotypically healthy males from the Zagreb area. Statistically significant differences to control were found in 13 variables in decreased ridge count in second, third, fourth and fifth finger on the right palm, and in their sum on the all five fingers, than in second, third, fourth and fifth finger on the left palm, and in their sum in the all fingers, and in the all ten fingers. Atd angle was decreased on the left palm, and on the both palm together. Accordingly a polygenetic system identical in some loci to polygenetic system predisposing to male psoriatic spondylitis susceptibility might be found responsible for dermatogliyphic pattern development.

Preventive CCL2/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheumatoid Arthritis by Reducing Homing of CCR2hi Osteoclast Progenitors to the Affected Bone.

Detailed characterization of medullary and extramedullary reservoirs of osteoclast progenitors (OCPs) is required to understand the pathophysiology of increased periarticular and systemic bone resorption in arthritis. In this study, we focused on identifying the OCP population specifically induced by arthritis and the role of circulatory OCPs in inflammatory bone loss. In addition, we determined the relevant chemokine axis responsible for their migration, and targeted the attraction signal to reduce bone resorption in murine collagen-induced arthritis (CIA). OCPs were expanded in periarticular as well as circulatory compartment of arthritic mice, particularly the CCR2hi subset. This subset demonstrated enhanced osteoclastogenic activity in arthritis, whereas its migratory potential was susceptible to CCR2 blockade in vitro. Intravascular compartment of the periarticular area contained increased frequency of OCPs with the ability to home to the arthritic bone, as demonstrated in vivo by intravascular staining and adoptive transfer of splenic LysMcre/Ai9 tdTomato-expressing cells. Simultaneously, CCL2 levels were increased locally and systemically in arthritic mice. Mouse cohorts were treated with the small-molecule inhibitor (SMI) of CCR2 alone or in combination with methotrexate (MTX). Preventive CCR2/CCL2 axis blockade in vivo reduced bone resorption and OCP frequency, whereas combining with MTX treatment also decreased disease clinical score, number of active osteoclasts, and OCP differentiation potential. In conclusion, our study characterized the functional properties of two distinct OCP subsets in CIA, based on their CCR2 expression levels, implying that the CCR2hi circulatory-like subset is specifically induced by arthritis. Signaling through the CCL2/CCR2 axis contributes to OCP homing in the inflamed joints and to their increased osteoclastogenic potential. Therefore, addition of CCL2/CCR2 blockade early in the course of arthritis is a promising approach to reduce bone pathology.

Health-related quality of life among patients with postmenopausal osteoporosis treated with weekly and monthly bisphosphonates.

OBJECTIVE: The present study was designed to assess the effect of monthly ibandronate on health-related quality of life (HR-QoL) in patients with postmenopausal osteoporosis previously treated with weekly bisphosphonates. METHODS: HR-QoL was assessed by Euroqol (EQ-5D) and Osteoporosis Targeted Quality of Life (OPTQoL) questionnaires. RESULTS: The EQ-5D questionnaire showed significant improvement associated with ibandronate treatment, occurring in mobility (p < 0.01), usual activity (p < 0.01), pain/discomfort (p < 0.05), and anxiety/depression (p < 0.05). In addition, ibandronate treatment considerably improved patients' perceived health on a visual analog scale (p < 0.001). For the OPTQoL questionnaire, patients reported less physical difficulty (p < 0.001), fewer adaptations in their lives (p < 0.001), and less fear (p < 0.001) with ibandronate than with weekly bisphosphonates. CONCLUSION: The study demonstrated that patients who were transferred from weekly bisphosphonates to a monthly ibandronate experienced improved HR-QoL.

Dermatoglyphics in psoriatic symmetrical polyarthritis in fifty women--quantitative analysis.

Quantitative dermatoglyphic analysis ofdigitopalmar ridge count was used to research psoriatic symmetrical polyarthritis in fifty women. Analyzed were 25 dermatoglyphics traits: number of epidermal ridges on all ten fingers, their sum for five and ten fingers, four traits on both palms, i.e., between a-b, b-c, c-d and a-d triradii, and atd angles and their bilateral sum. The data obtained were compared with those recorded in a control group of 200 pairs of imprints of phenotypically healthy females from Zagreb area. Statistically significant differences were found in 13 variables in decreased ridge count in all ten fingers, their sum in five and ten fingers separately. Accordingly, a polygenetic system identical in some loci to polygenic system predisposing to women psoriatic symmetrical polyarthritis susceptibility might be found responsible for the dermatoglyphic pattern development.

Dermatoglyphics of digitopalmar complex in forty male patients affected by rheumatoid arthritis--quantitative analysis.

Quantitative analysis of digitopalmar ridge count was performed in forty male patients with rheumatoid arthritis to evaluation of genetic factors in that disease. Twenty five variables (ridge count on each of ten fingers, their sum on five and ten fingers, four traits on each palm, i. e. ridge count between a-b, b-c and c-d triradii, their sum on each and both palm and at angle on two palms and their bilateral sum) were determined. The data thus obtained were compared with digitopalmar prints of 200 healthy men who served as a control group. A significant difference from the control group was found in eight variables. Ridge count was increased on the first and fifth finger bilaterally, on the fourth right finger tip, and their sum on each, and both fists. Accordingly, a polygenic system identical in some loci to the polygenic system predisposing to rheumatoid arthritis susceptibility might be found responsible for the dermatoglyphic pattern development. That means that they could used, and that is the aim of this study, as a diagnostic tool in rheumatic diseases.

[Proposal of Croatian Society for Rheumatology for anti-TNF-alpha therapy in adult patients with spondyloarthritides]. / Prijedlog Hrvatskog reumatoloskog drustva za primjenu inhibitora TNF-alpha u odraslih bolesnika sa spondiloartritisima.

Spondyloarthritides (SpA) as a group are one of the most common rheumatic disorders with a predominant affection of the spine. Conventinal disease modifying antirheumatic drugs which are effective in rheumatoid arthritis have poor effect on spinal inflammation. Today there is confirmed efficacy ofbiologics in spondylitis. This therapy is expensive and potentially hazaradous. Croatian Society for Rheumatology set up recommendations for the use of TNF-alpha blockers in SpA. There are several important points to be considered before their use: diagnosis of Spa, duration and disease activity, previous therapy and it's efficacy, application and efficacy ofbiologics, contraindications and safety preacutions and finally a decision for continuous tretament with biologics.

Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells.

BACKGROUND: The peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: PB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy. Receptors for osteoclastogenic factors (CD115 and receptor activator of nuclear factor-κB [RANK]) and selected chemokines (CC chemokine receptor 1 [CCR1], CCR2, CCR4, CXC chemokine receptor 3 [CXCR3], CXCR4) were determined in an OCP-rich subpopulation (CD3-CD19-CD56-CD11b+CD14+) by flow cytometry. In parallel, levels of CC chemokine ligand 2 (CCL2), CCL3, CCL4, CCL5, CXC chemokine ligand 9 (CXCL9), CXCL10, and CXCL12 were measured using cytometric bead array or enzyme-linked immunosorbent assay. Sorted OCPs were stimulated in culture by macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand, and they were differentiated into mature osteoclasts that resorb bone. Selected chemokines (CCL2, CCL5, CXCL10, and CXCL12) were tested for their osteoclastogenic and chemotactic effects on circulatory OCPs in vitro. RESULTS: The OCP population was moderately enlarged among PB cells in RA and correlated with levels of tumor necrosis factor-α (TNF-α), rheumatoid factor, CCL2, and CCL5. Compared with PB, the RANK+ subpopulation was expanded in SF and correlated with the number of tender joints. Patients with PsA could be distinguished by increased RANK expression rather than total OCP population. OCPs from patients with arthritis had higher expression of CCR1, CCR2, CCR4, CXCR3, and CXCR4. In parallel, patients with RA had increased levels of CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10, with significant elevation in SF vs PB for CXCL10. The subset expressing CXCR4 positively correlated with TNF-α, bone resorption marker, and rheumatoid factor, and it was reduced in patients treated with disease-modifying antirheumatic drugs. The CCR4+ subset showed a significant negative trend during anti-TNF treatment. CCL2, CCL5, and CXCL10 had similar osteoclastogenic effects, with CCL5 showing the greatest chemotactic action on OCPs. CONCLUSIONS: In our study, we identified distinct effects of selected chemokines on stimulation of OCP mobilization, tissue homing, and maturation. Novel insights into migratory behaviors and functional properties of circulatory OCPs in response to chemotactic signals could open ways to new therapeutic targets in RA.

[Therapeutic ultrasound in chronic low back pain treatment]. / Terapijski ultrazvuk u lijecenju bolesnika s kronicnom krizoboljom.

The purpose was to determine the efficacy of therapeutic ultrasound in patients with chronic low back pain. Thirty-one patients, age 38-77, with low back pain lasting more than three months and the intensity of pain on visual analogue scale at least 50 mm, are randomly divided in two groups. Ultrasound is applied on the lumbar paravertebral muscle in 16 patients and in 15 patients the machine was not switched on. All patients also underwent kinesitherapy. Pharmacological treatment was not changed during the research (except the possibility of using paracetamol as the "rescue drug"). Following parameters were measured at the beginning and at the end of the research: pain intensity on the visual analogue scale/mm, modified Schober measure/cm, patient's and physician's global assessment of treatment efficacy (1-5 scale). The intensity of pain in the ultrasound group before the treatment was 82,7+/-14,0 and after the treatment 79,8+/-12,2 (p<0,05). The intensity of pain in the placebo group before the treatment was 81,7+/-12,1 and at the end of the treatment 78,9+/-12,1 (p>0,05). The value of the modified Schober measure for the ultrasound group were 5,7+0,8 cm vs. 5,8+/-0,9 cm (p>0,05) and in the placebo group were 5,4+/-0,9 cm vs. 5,6+/-1,0 cm (p>0,05). There was no significant statistical difference between ultrasound and placebo group regarding the efficacy of the treatment (patients p>0,05, physicians p>0,05). Therapeutic ultrasound was effective in decreasing the pain intensity in this research, but showed no improvement regarding the functional ability of the lumbar spine in patients with chronic low back pain.

A contribution to genetic etiology of complex regional pain syndrome type I (algodystropy syndrome) based on quantitative analysis of digitopalmar dermatoglyphics in sixty men.

The patterns of the ridges of the skin of the fingers and palms were determined in sixty men with complex regional pain syndrome (type I) as a measure of disease prevention. The study included 25 dermatoglyphic traits: number of epidermal ridges on all ten fingers; their sum for five and ten fingers; four traits on both palms, i.e. between a-b, b-c and c-d triradii; atd angles: and their bilateral sum. The data obtained were compared with those recorded in a control group of 200 pairs of imprints of phenotipycally healthy male adults from the Zagreb area. Statistically significant difference from control values were found in 12 dermatoglyphic variables, including an increased sum of ridges on nine fingers (except for left second finger pad), and total sum for five and ten fingers. These findings suggested the polygenic system responsible for development of dermatoglyphics to be identical with some polygenic loci for the onset of algodystrophy syndrome, which might prove useful in disease prevention (e.g., taking fingerprints following a trauma and before rehabilitation), and to facilitate identification of risk groups, and thus the treatment for this longterm and yet obscure syndrome.

[Prevalence of psoriatic arthritis in a population of patients with psoriasis]. / Ucestalost psorijaticnog artritisa u populaciji bolesnika s psorijazom.

UNLABELLED: Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease characterized by arthritis associated with psoriasis. AIM OF THE STUDY: The aim of the study was to determine the prevalence of psoriatic arthritis in a population of patients with psoriasis. According to literature data, its prevalence varies between 1% and 7%, or only exceptionally more. PATIENTS: Seventy-two adult patients with psoriasis were examined. Patients came from the north-west part of Croatia, from different towns with the overall population of more than 150,000, thus making a representative epidemiological sample. Some patients were treated by a dermatologist, whereas others were admitted to rheumatology departments for the problems with locomotor system and were diagnosed as psoriatics. All patients were examined, and their data were processed. RESULTS: Statistical analysis showed the two sexes to be equally involved by psoriasis. In most cases psoriasis preceded arthritis. All arthritis patients had their fingernails affected with psoriasis. In the population of patients with psoriasis, the prevalence of arthritis was higher in men (60%) than in women (40%). Arthritis often occurred (37.5%) in patients with psoriasis localized in the inguinal and/or perianal region with toenail involvement, as compared to 8.9% of patients with arthritis without concurrent psoriasis involvement. CONCLUSION: The prevalence of arthritis in psoriasis patients was 15.3%.

[Hip in rheumatic diseases]. / Kuk u reumatskim bolestima hip in rheumatic diseases.

The clinical diagnosis of hip pain is based on functional anatomy knowledge, detailed medical history and careful physical examination of the joints, periarticular soft tissue, nerve and blood supply, abdomen and thoracolumbal spine. Pain in the hip region may arise from the hip itself, adjacent bones or periarticular soft tissue and in addition thoracolumbal spine disorders, intraabdominal pathologies and peripheral vascular diseases can present with reffered pain in this region. Pain is the main symptom and it can be accompanied with morning stiffness and presence of systemic symptoms such as fatique, fever, weight loss or worsening of pain at night. Althought the technology for diagnostic testing is well developed, a detailed history is still as well as careful physical examination, essential for the precise diagnosis.

[Painful shoulder syndrome]. / Sindrom bolnog ramena.

Painful shoulder syndrome was described by S.E. Duplay 1872. showing the patient with pain and stiffness of the shoulder after trauma. Codman et. al. at the beginning of 20th century expanded the syndrome on several causes of shoulder pain. Syndrome is characterized by pain and limitation of joint movements. One of the most common nontraumatic causes of shoulder pain is periarticular disorder. The potential sources of local or referred pain may be muscle, tendon, bursa or neurovascular structures. Secondary referral pain to the shoulder may be due to coronary artery disease, hepatic or splenic disease.

[Comparison of standard and acupuncture methods of transcutaneous electric nerve stimulation (TENS) in patients with rheumatoid arthritis]. / Usporedba standardne i akupunkturi slicne transkutane elektricne zivcane stimulacije (TENS) u bolesnika s reumatoidnim artritisom.

The comparison of standard high frequency (ST-TENS) and acupuncture-like TENS (AL-TENS) in patients with rheumatoid arthritis is presented. Thirty-three patients (26 women and 7 men) with rheumatoid arthritis (according to modified ACR criteria), and with the duration of the disease 10.7 +/- 8.8 years are investigated. Each subject received ST-TENS (75 Hz) at the selected joint and AL-TENS (4 Hz) at the contralateral joint respectively. No significant difference between left and right side in pre-treatment pain was the main criterion for selecting the treated joint. Treatment was performed during 12 days. The initiation, duration, level of hypolgesia (according to Ritchie's pain assessment scale and VAS), patients' global assessment and possible reduction of dosage of analgetics/antirheumatics were measured. There was a significant reduction in pain level on ST-TENS site (48.6%), and on AL-TENS site (40.8%), measured on VAS. Results of Ritchie's index showed significant difference before and after application (for each type of TENS P < 0.05). There was no statistical difference between both types of TENS regarding the reduction of pain level, as well as the initiation of analgesic effect, whilst it was noted a slightly longer, although statistically not significant, hypoalgesic effect of AL-TENS. Patients' global assessment also did not differ relating to ST-TENS and AL-TENS, as well as their opinion on possible dosage reduction of analgetics/antirheumatics. Side effects for both types of TENS were negligible. The findings showed that ST-TENS and AL-TENS provided hypoalgesic effect in the similar degree in patients with long-standing rheumatoid arthritis.

[Treatment of chronic pain--use of transdermal fentanyl (Durogesic TTS)]. / Lijecenje Kronicne boli--primjena transdermalnog fentanila (Durogesic TTS).

Incorrect treatment of chronic pain is common cause of patient's discontentment and suffering. The problem is mostly occurring because of inappropriate pain treatment. The WHO guidelines recommends declining of prejudices and using of strong opioids in therapy after the unsatisfactory treatment with weaker analgesics. Strong opioid analgesic fentanyl in transdermal system (Durogesic TTS) is introduced. In rheumatology, it is recommended for all conditions characterised by chronic pain with intensity 4 and more on the VAS scale (0-10). It is mostly used in rheumatoid arthritis, osteoarthritis, low back pain and neuropathic pain. Durogesic TTS provides continuous pain relief for 72 hours, with constant serum concentrations. It has to be gradually titrated and starting dose is 25 micrograms/h. Possible adverse events (nausea, vomiting, constipation, sedation, itching) are short termed, transitory and easily managed. Results of some clinical trials and personal experiences that are proving its efficacy and safety are presented.

Monthly or weekly bisphosphonate? Evaluation of satisfaction in patients with postmenopausal osteoporosis using OPSAT-Q questionnaire during the BOOSTER study in Croatia.

A prospective, open-labelled, multicentre 6-month study was designed to assess three categories that have high impact on Health-Related Quality of Life (HR-QoL). These categories were: satisfaction, preference and drug tolerability in postmenopausal patients with osteoporosis in Croatia, at first treated with weekly oral bisphosphonates, followed by monthly oral ibandronate. Three hundred eighty-five postmenopausal women who were treated with one of the weekly bisphosphonates for at least 6 months were included into the study and after they had signed written informed consent, the therapy was changed to monthly ibandronate. Satisfaction with the treatment was assessed with the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q). Patients completed OPSAT-Q at the baseline visit before the change of therapy (visit 1) and 6 months after the change of therapy (visit 2). Following 6 months ibandronate therapy, the values in all four domains of the OPSAT-Q (convenience, confidence with daily activities, overall satisfaction, side effects) as well as in the Composite Satisfaction Score were higher in visit 2 (p < 0.001). Values in subjects enrolled into the patient assistance programme did not differ significantly from the values in subjects that were not (p = 0.399) except for the domain convenience (p = 0.026). This study demonstrates significantly higher satisfaction in patients who switched from the weekly bisphosphonate therapy regimen to monthly ibandronate in all observed aspects of treatment. Patients expressed preference for monthly bisphosphonate (ibandronate) in comparison with weekly bisphosphonates and found it to be a more convenient method of treatment. At the time of study, however, it was not known that the anti-fracture effect of ibandronate was smaller for hip fractures than with other bisphosphonates.