Adherence to the Mediterranean diet is associated with a reduced DAS28 index among patients with rheumatoid arthritis: Case study from KRRD.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, autoimmune disease that mostly affects the synovial joints. It has been hypothesized that dietary and other environmental and lifestyle factors contribute to the development of RA and its severity. OBJECTIVE: The present study aims to measure the effect of the Mediterranean diet (MedDiet) on the disease activity scores (DAS28) among patients with RA. METHODS: Adult patients who satisfied the American College of Rheumatology (ACR) classification criteria for RA from major hospitals in Kuwait were evaluated. A cross-sectional study conducted on 754 RA patients visits aged (21-79) years. Patients were evaluated using the DAS28. Patients' levels of adherence to the MedDiet are assessed using a validated 14-item Questionnaire (paper or web-based). The data was analyzed using both multivariate and univariate statistics. Multivariate logistic regression was used to analyze the statistical relationship between MedDiet and RA disease activity. RESULTS: The finding suggests that a MedDiet can have a positive impact on DAS28 among patients with RA. In the DAS28 cohort (DAS28 < 3.2, DAS28 ≥ 3.2), several Mediterranean survey components showed statistically significant differences. Patients with a Mediterranean score ≤ 5 was more likely to have hazard effects for DAS28 than those with a Mediterranean score of ≥10 (HR = 0.17, CI [0.08-0.37], p < .001). The finding shows that, Mediterranean levels ≤5, on biologics treatment, CRP, and patient global assessment were significantly associated with overall survival. Additionally, the MedDiet was found to be a significant predictor of DAS28 in the random forest decision tree plot, along with tender, RF, and creatinine. MedDiet patients had a lower DAS28 score than others. CONCLUSION: The findings suggest that optimal drug treatment and a restrictive diet can help to improve DAS28 score for patients with RA. More patients in the cohort DAS28 <3.2 used olive oil, servings of vegetables, fruits, and legumes. In contrast, more patients in the cohort DAS28 ≥ 3.2 consumed red meat, butter, sweetened or soft drinks, cakes, cookies, or biscuits, and tomato sauce.

Accessibility to biologics and its impact on disease activity and quality of life in patients with rheumatoid arthritis in Kuwait.

OBJECTIVE: Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or patients with contraindications to cDMARDs or poor prognostic factors. The purpose of this study was to compare the prescription rates of biologics in Kuwaiti and non-Kuwaiti patients and to assess whether this had an impact on disease activity and quality of life in RA patients. METHODS: Data were extracted from the Kuwait Registry for Rheumatic Diseases. Adult patients who satisfied the ACR classification criteria for RA from four major hospitals in Kuwait were evaluated from February 2013 through May 2018. The treatment agents, disease activity, and quality of life of Kuwaiti patients were compared with non-Kuwaiti patients. RESULTS: A total of 1651 RA patients were included; 806 (48.8%) were Kuwaiti patients. Among Kuwaiti patients, 62.5% were on biologic drugs in comparison with 14% of non-Kuwaiti patients. In comparison with non-Kuwaiti patients, Kuwaiti patients had significantly lower numbers of swollen joints (p < 0.001) and disease activity score-28 scores (p = 0.02) and less steroid use (p < 0.001) yet a significantly higher health assessment questionnaire-disability index (p < 0.001). Regression analysis showed that DAS-28 scores were significantly associated with the treatment type (p < 0.001) and that nationality was significantly predictive of the treatment type (p < 0.001). CONCLUSION: In the setting of easy accessibility to treatment for Kuwaiti patients, biologics were prescribed by rheumatologists at a higher rate than for non-Kuwaitis. This may explain the lower disease activity and the lower rate of steroid use in Kuwaiti patients than non-Kuwaitis. KEY POINTS: • Significant discrepancies in the rates of prescribing biologic therapies between KP and NKP in Kuwait were observed. • Several treatment outcomes were significantly better in the KP group than in the NKP group even after adjustment of confounding factors. • The poor access to biologic therapies was suggested to limit the effectiveness of RA treatments in the NKP group.

Kuwait association of rheumatology 2018 treatment recommendations for patients with rheumatoid arthritis.

The Kuwait Association of Rheumatology (KAR) aimed to develop a set of recommendations for the treatment of patients with rheumatoid arthritis (RA), tailored to the unique patient population and healthcare system of Kuwait. Each recommendation was developed based on expert opinion and evaluation of clinical practice guidelines from other international and national rheumatology societies. Online surveys were conducted to collate feedback on each KAR member's level of agreement (LoA) with definitions of disease-/treatment-related terms used and the draft recommendations. Definitions/recommendations achieving a pre-defined cut-off value of ≥ 70% agreement were accepted for inclusion. Remaining statements were discussed and revised at a face-to-face meeting, with further modifications until consensus was reached. A final online survey was used to collect feedback on each KAR member's LoA with the final set of recommendation statements on a scale of 0 (complete disagreement) to 10 (complete agreement). Group consensus was achieved on 66 recommendation statements, including 3 overarching principles addressing the pharmacological treatment and management of RA. Recommendations focused on treatment of early RA, established RA, patients with high-risk comorbidities, women during pregnancy and breastfeeding, and screening and treatment of opportunistic infections. The KAR 2018 Treatment Recommendations for RA reported here are based on a synthesis of other national/international guidelines, supporting literature, and expert consensus considering the Kuwaiti healthcare system and RA patient population. These recommendations aim to inform the clinical decisions of rheumatologists treating patients in Kuwait, and to promote best practices, enhance alignment and improve the treatment experience for patients.

High prevalence of protein tyrosine phosphatase non-receptor N22 gene functional variant R620W in systemic lupus erythematosus patients from Kuwait: implications for disease susceptibility.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease which involves the loss of self-tolerance with hyperactivation of autoreactive T- and B-cells. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) encodes for lymphoid specific phosphatase (LYP) which is a key negative regulator of T lymphocyte activation. The aim of this study was to investigate the association between PTPN22 gene functional variant R620W and systemic lupus erythematosus (SLE) by comparing its prevalence in Kuwaiti SLE patients and controls. METHODS: The study included 134 SLE patients and 214 controls from Kuwait. The genotypes of PTPN22 gene functional variant R620W were determined by PCR-RFLP and confirmed by DNA sequence analysis in both SLE patients and the controls. RESULTS: A relatively high prevalence of the variant 620 W (T-allele) of the PTPN22 gene was detected in the SLE patients from Kuwait. 35.7% of the SLE patients had at least one variant allele (T-allele) compared to 15.9% in the controls. A statistically significant difference was detected in the frequency of variant genotypes, TT and CT between SLE patients and the controls (p < 0.0001). No association was detected between the PTPN22 gene variant and the Raynaud's phenomenon, renal involvement and severity of the SLE. CONCLUSIONS: The frequency of PTPN22 gene functional variant R620W reported in this study is amongst the highest compared to other world populations. A high prevalence of this variant in SLE patients in comparison to the healthy controls suggests its significant contribution in conferring susceptibility to SLE together with other factors.

Low Prevalence of Nodules in Rheumatoid Arthritis Patients in Kuwait: A Description and a Comparison of Patients from the Kuwait Registry for Rheumatic Diseases.

OBJECTIVES: To describe the prevalence of rheumatoid nodules (RN) in patients with rheumatoid arthritis (RA) and to compare their features with those of patients without RN. SUBJECTS AND METHODS: Adult RA patients (n = 952) in the Kuwait Registry for Rheumatic Diseases from February 2013 to December 2015 were evaluated for RN. Demographic and serological features and disease activity and severity were obtained from the registry. RESULTS: Of the 952 RA patients, 22 (2.3%) had RN and 930 (97.7%) did not. Age, sex, disease duration, smoking, and family history of an autoimmune rheumatic disease were similar. Obesity was more prevalent in the RN group, i.e. 11 (50%) vs. 326 (35.1%), p = 0.016. There was no difference in rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody positivity. Patients with RN had more sicca symptoms, i.e. 8 (36.4%) vs. 152 (16.3%), p = 0.025, a higher mean score on the visual analogue scale pain (3 ± 2.9 vs. 2 ± 2.7, p < 0.001), more tender joints (6.4 ± 8.8 vs. 4.2 ± 7.2, p = 0.001), a higher patient global assessment of disease activity (3.3 ± 2.7 vs. 2.3 ± 2.7, p < 0.001), and more deformities, i.e. 3 (13.6%) vs. 74 (8%), p = 0.034. The mean health assessment questionnaire score in RN patients was 1.1 versus 0.9 in patients without RN (p = 0.08). Patients with RN had a low disease activity (means: disease activity score [DAS-28], 3.02; clinical disease activity index, 7.7; and simple disease activity index, 10.4), similar to the other group. While the rates of methotrexate treatment were comparable, biologic therapy was administered more in patients with RN (i.e. 15 [68.2%] vs. 478 [51.4%], p < 0.001). CONCLUSION: In Kuwait, the prevalence of RN is low among RA patients. Patients with and without RN are similar in terms of demographics and serologic features, except for more obesity. However, patients with RN have more sicca symptoms, joint deformities, and painful and tender joints. Disease activity scores are low with more frequent biologic therapy.

Safety, Tolerability, and Efficacy of Tocilizumab in Rheumatoid Arthritis: An Open-Label Phase 4 Study in Patients from the Middle East.

This open-label study investigated the safety and efficacy of tocilizumab in Middle Eastern patients with rheumatoid arthritis (RA). Patients whose Disease Activity Score based on 28 joints (DAS28) was >3.2 received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks. Patients receiving aTNF ± nonbiologic disease-modifying antirheumatic drug(s) (DMARD(s)) switched to tocilizumab; patients receiving nonbiologic DMARD monotherapy added tocilizumab. Primary end points were adverse events (AEs), serious AEs (SAEs), and laboratory parameters; secondary end points were DAS28, Health Assessment Questionnaire-Disability Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Eighty-eight of 95 patients completed 24 weeks. Overall, 125 AEs were reported in 43 (45%) patients; the most common were increased hepatic enzymes (16%) and cholesterol (11%). Eight patients experienced SAEs. Significant changes from baseline to week 24 occurred for hemoglobin, neutrophils, platelets, total cholesterol, and liver enzymes (P < 0.05). DAS28, CRP, and ESR decreased significantly from baseline at each visit (P < 0.0001). At week 24, the proportions of patients reporting DAS28 clinically meaningful improvement (decrease ≥1.2), low disease activity (DAS28 ≥2.6 to ≤3.2), and remission (DAS28 <2.6) were 92%, 23%, and 64%, respectively. Safety and efficacy of tocilizumab were consistent with values reported in Western patients.

Amelioration of human osteoarthritis symptoms with topical 'biotherapeutics': a phase I human trial.

Osteoarthritis (OA) treatments presently rely on analgesics, which manage pain but fail to restore imbalances between catabolic and anabolic processes that underlie OA pathogenesis. Recently, biologic (biotherapeutic) drugs, which alter the activity of catabolic agents such as nitric oxide and inflammatory cytokines in ways, allowing tissue regeneration, were evaluated for efficacy in OA treatment. These studies failed to demonstrate dramatic abatement of OA symptoms by these drugs, but suggested strategies by which biologic agents might be used to treat OA. The present review summarizes current understanding of OA pathogenesis and evolving treatments. Preliminary evaluations of a novel biotherapeutic strategy are presented here. Twenty OA patients receiving sour topical cherry seed extract (SCE), an inducer of heme oxygenase-1 (HO-1), a major physiological protectant against oxidative stress exhibited significantly decreased joint pain and activation of CD4+ T cells expressing inflammatory cytokines (p < 0.05), significantly decreased peripheral blood C-reactive protein (CRP), and increased leukocyte HO-1 (p < 0.05) in comparison with ten placebo-treated patients. SCE inhibits joint-damaging inflammatory mediator production. This agent therefore meets the main criterion for classification as a "biotherapeutic," or "biologic" agent. The negligible toxicity and low cost of such materials make them promising contributors to OA treatment, sustainable within resource limitations of a wide range of patients.

Sour cherry (Prunus cerasus) seed extract increases heme oxygenase-1 expression and decreases proinflammatory signaling in peripheral blood human leukocytes from rheumatoid arthritis patients.

Sour cherry seed extract (SCE) was evaluated for its capacity to inhibit lipopolysaccharide-treated human peripheral blood T cells expressing tumor necrosis factor-alpha, and the chemokine interleukin-8. Both proteins are diagnostic biomarkers for inflammatory pathologies. Peripheral blood leukocytes from 11 rheumatoid arthritis (RA) patients and 8 healthy control subjects were co-cultured for 24h in lipopolysaccharide and the extract, then evaluated by flow cytometry for T cell activation and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1) expression. There was a dose-dependent decrease in expression of the immunophenotypes: CD3+TNF-α+, and CD3+IL8+ in cultures from RA patients to a greater extent than in cells from healthy participants. These results suggest that the extract may have a modulatory roll in RA and other inflammatory disorders via the induction of HO-1, thus abating oxidative stress and strengthening regulation of pro-inflammatory signaling pathways.

Can lenalidomide play a role in the management of scleritis?

Lenalidomide is an immunomodulatory agent that was approved for the treatment of a monoclonal bone marrow disorders, myelodysplastic syndrome del(5q)(MDS del(5q)), in 2005; the drug was subsequently also approved for the treatment of refractory multiple myeloma, a bone marrow malignancy of the B-lymphocyte lineage. The purpose of this study is to report a case of MDS del(5q) in a female patient, which was most likely secondary to the immunosuppressive drugs that the patient was taking for scleritis. After lenalidomide treatment, the patient's haematological symptoms rapidly resolved and she became transfusion independent, with normal haemoglobin levels. This medication also helped control her dependence on high doses of oral prednisolone. The patient continued to receive treatment with low-dose lenalidomide, and her scleritis has been in long-term remission for 3 years. A larger prospective study can further define the role of lenalidomide in the management of scleritis.

Suboptimal management of rheumatoid arthritis in the Middle East and Africa: could the EULAR recommendations be the start of a solution?

Although the prevalence of RA in the Middle East and Africa is comparable with that in other parts of the world, evidence indicates that its management in this region is suboptimal for a variety of reasons, including misconceptions and misunderstandings about the disease's prevalence and severity in the region, compounded by the lack of local epidemiological and health-economic data around the disease; the perception that RA is a low priority compared with other more prevalent conditions; delayed diagnosis, referral and treatment; and a lack of a region-specific, evidence-based management approach. In the absence of such an approach, the EULAR treatment recommendations may provide a useful starting point for the creation of guidelines to suit local circumstances. However, although agreement with the EULAR recommendations is high, many barriers prevent their implementation in clinical practise, including lack of timely referral to rheumatologists; suboptimal use of synthetic DMARDs; poor access to biologics; lack of awareness of the burden of RA among healthcare professionals, patients and payers; and lack of appropriate staffing levels.To optimise the management of RA in the Middle East and Africa, will require a multi-pronged approach from a diverse group of stakeholders-including local, national and regional societies, such as the African League of Associations in Rheumatology and International League of Associations for Rheumatology, and service providers-to collect data on the epidemiology and burden of the disease; to increase awareness of RA and its burden among healthcare professionals, payers and patients through various educational programmes; to encourage early referral and optimise use of DMARDs by promoting the EULAR treatment recommendations; to encourage the development of locally applicable guidelines based on the EULAR treatment recommendations; and to facilitate access to drugs and the healthcare professionals who can prescribe and monitor them.

Effects of rituximab treatment on the serum concentrations of vitamin D and interleukins 2, 6, 7, and 10 in patients with rheumatoid arthritis.

BACKGROUND: Rituximab, a monoclonal antibody that selectively targets CD20-positive B-lymphocytes, is used for the treatment of patients with rheumatoid arthritis (RA) with an inadequate response or tolerance to tumor necrosis factor inhibitors. The objective of this study was to investigate the effects of rituximab treatment on the serum concentrations of vitamin D, interleukin (IL) 2, IL-6, IL-7, and IL-10 in patients with rheumatoid arthritis (RA). METHODS: Forty-five patients, aged 25-78 years, were enrolled into a cohort prospective study. All patients were treated with intravenous rituximab. Disease activity score-28 (DAS-28) and serum concentrations of rheumatoid factor (RF), C-reactive protein (CRP), anticyclic citrullinated peptide (anti-CCP), erythrocyte sedimentation rate (ESR), health assessment questionnaire (HAQ), vitamin D, ILs 2, 6, 7, and 10 were estimated in the patients before and after treatment with rituximab. RESULTS: DAS-28, HAQ score, and serum concentrations of CRP, RF, anti-CCP, IL-2, IL-6, IL-7, IL-10, and ESR significantly decreased after treatment. All 45 patients had vitamin D deficiency before treatment and this did not significantly change after treatment. However no significant association was found among serum vitamin D concentration and any of the ILs. CONCLUSION: We concluded from this study that although rituximab treatment of patients with RA significantly reduced their disease activity and serum concentrations of IL-2, IL-6, IL-7, and IL-10, it did not significantly alter their vitamin D status. Furthermore, no significant association was found among serum vitamin D concentration and any of the ILs.

Are 25(OH)D levels related to the severity of knee osteoarthritis and function?

OBJECTIVE: To investigate the effect of 25-hydroxyvitamin D [25(OH)D] in Kuwaiti patients with primary knee osteoarthritis (OA) and to assess its relation with radiological grading and functional status. SUBJECTS AND METHODS: In this cross-sectional study, 25(OH)D was measured using radioimmunoassay in 99 patients [90 women and 9 men; mean age 56.5 ± 9.1 years (range: 36-80)] with clinical and radiological findings of primary knee OA. X-ray grading using the Kellgren-Lawrence grading scale and the Osteoarthritis Research Society International (OARSI) Atlas grading scale and functional assessments using Lequesne's indices were evaluated in relation to the 25(OH)D level. Other variables studied were age at onset of symptoms, body mass index and duration of disease. RESULTS: The age of the patients at the onset and the duration of disease were 51.58 ± 7.14 and 3.88 ± 2.51 years, respectively. Mean scoring for functional assessment was 10.31 ± 4.35 and mean Kellgren-Lawrence radiological grading was 2.43 ± 0.85. Radiological finding according to the OARSI Atlas revealed joint space narrowing of grades 2-3 in 87 (87.9%) patients and the presence of osteophytes in 55 (55.6%) patients. The mean value of 25(OH)D level was 11.4 ± 6.07 ng/ml. Of the 99 patients, 92 (92.9%) were vitamin D deficient. Comparison of 25(OH)D levels to radiological findings and different functional classes showed no significant association. CONCLUSION: Most of our patients had vitamin D deficiency, but the level of 25(OH)D was not related to the severity of the knee X-ray grading or to the functional assessment in our patients with primary knee OA.

Inter- and intraobserver variation between radiologists in the detection of abnormal parenchymal lung changes on high-resolution computed tomography.

BACKGROUND AND OBJECTIVES: Radiological and histological evaluations are affected by subjective interpretation. This study determined the level of inter- and intraobserver variation among radiologists for detection of abnormal parenchymal lung changes on high resolution computed tomography (HRCT). METHODS: HRCT images of 65 patients known to have systemic lupus erythematosus (with clinical pulmonary involvement) were retrospectively reviewed by four nonthoracic radiologists (two with expertise in magnetic resonance [MR] and two general radiologists). Each radiologist read the scans twice, with an interval between readings of at least 6 months. The interobserver variation among the first and second readings of the four radiologists and the intraobserver variation of each radiologist's two readings were assessed by the kappa statistic. RESULTS: There was good agreement between the first and second readings of each radiologist. There was moderate agreement between the two readings of one MR radiologist (kappa=0.482); the other three radiologists had kappa values that were good to excellent (0.716, 0.691, and 0.829). There was a clinically acceptable level of interobserver variability between all radiologists. The agreement was fair to moderate between the MR radiologist and the other observers (kappa range: 0.362-0.519) and moderate to good between the other three radiologists (0.508-0.730). CONCLUSION: The interpretation of imaging findings of abnormal parenchymal lung changes on HRCT is reproducible and the agreement between general radiologists is clinically acceptable. There is reduced agreement when the radiologist is not involved on a regular basis with thoracic imaging. Difficult or indeterminate cases may benefit from review by a chest radiologist.

Association of angiotensin-converting enzyme (ACE) gene insertion-deletion polymorphism with spondylarthropathies.

Low back pain (LBP) is a common medical problem. Interaction between genetic and environmental factors predisposes individuals to LBP even at an early age. Inflammatory back pain or spondylarthropathies include ankylosing spondylitis (AS), psoriatic arthritis (PSA), reactive arthritis enteropathic and undifferentiated arthropathies. Angiotensin-converting enzyme (ACE) plays an important role in circulatory homeostasis, physiology of vasculature and inflammation. The insertion-deletion (I/D) polymorphism of the ACE gene has been shown to determine the plasma and tissue levels of ACE especially in the synovial fluid. The aim of this study was to investigate an association between ACE gene I/D polymorphism and inflammatory back pain (spondylarthropathies) secondary to ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel disease and undifferentiated spondylarthropathies. The prevalence of ACE gene I/D polymorphism genotypes was determined in 63 patients with inflammatory back pain by polymerase chain reaction (PCR) and compared with that in 111 healthy controls. Of the 63 patients studied, 45 (71.4%) were with AS, 13 (20.6%) were with PSA, 4 (6.3%) were with reactive arthropathy and 1 (1.6%) manifested undifferentiated arthropathy. There were 43 males and 20 females. Mean age of patients was 39.0+/-11.36 years, age at onset of spondylarthropathy was 27.7+/-7.49 years and disease duration was 10.3+/-7.74 months. The controls were selected to match with the patients group in terms of gender ratio, age and ethnicity. The ACE gene polymorphism showed an overall significant difference between patients and controls (p=0.050). When the ID and II genotype frequency was combined and compared with that for DD genotype amongst patient and control groups, a considerably higher incidence was detected for ID and II genotypes than the DD genotype in spondylarthropathy patients compared to that in the controls (p=0.036). This study showed a significant association of the I-allele of ACE gene I/D polymorphism with spondylarthropathy in Kuwaiti Arabs.

Angiotensin-converting enzyme gene polymorphism in patients with psoriatic arthritis.

To investigate the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism genotypes in adults with psoriatic arthritis (PsA), a heterogeneous chronic disease with autoimmune pathology. ACE gene I/D polymorphism influences the plasma and tissue levels of ACE and has an involvement in inflammatory mechanism. The frequency of ACE gene I/D polymorphism genotypes was determined in 51 adults with PsA from Kuwait, and compared to that in 100 ethnically matched healthy controls using polymerase chain reaction. The distribution of ACE I/D polymorphism and allele frequencies in PsA patients were not significantly different from controls (P > 0.05). Further analyses of PsA patients showed that ACE I/D gene polymorphism was not associated with family history, clinical manifestations, and disease severity. However, the frequency of II genotype was significantly higher in patients with late disease onset than in those with early onset (25 vs. 3%; P = 0.04). No difference was found between the distribution of the ACE genotype in PsA patients and the general population in Kuwait. However, the presence of II genotype may confer susceptibility to the development of late onset PsA.

Lupus patients with pulmonary involvement have a pro-inflammatory cytokines profile.

OBJECTIVES: The literature on cytokine response in systemic lupus erythematosus (SLE) is confusing. It is possible that different disease phenotypes have different cytokine profiles. Our aim was to examine the levels of selected pro-inflammatory and anti-inflammatory cytokines in SLE patients with and without pulmonary involvement. METHODS AND SUBJECTS: Patients with SLE were interviewed and were subjected to the pulmonary function test and high-resolution computed tomography studies. Serum levels of interleukin (IL)-6, IL-8, IL-10, Il-12, interferon (IFN) gamma, and tumor necrosis factor (TNF) alpha were estimated by enzyme-linked immunosorbent assay. RESULTS: Forty-nine of the 61 SLE patients had pulmonary involvement. Median levels of IL-8, IFNgamma, and TNFalpha were significantly higher in the pulmonary group as compared to the non-pulmonary group (p = 0.027, 0.027 and 0.002, respectively). Ratios of pro-inflammatory cytokines to anti-inflammatory cytokines were higher in the pulmonary group as compared to the non-pulmonary group as well as in the pulmonary restrictive subgroup compared to the obstructive subgroup. CONCLUSION: Lupus patients with pulmonary involvement have a stronger pro-inflammatory cytokine bias than those without pulmonary involvement.

Incidence of musculoskeletal pain in adult Kuwaitis using the validated Arabic version of the WHO-ILAR COPCORD Core Questionnaire.

BACKGROUND: The WHO-ILAR Community Oriented Program for Control of Rheumatic Diseases (COPCORD) primarily aims to estimate the burden of musculoskeletal symptoms/disorders. We estimated the incidence of musculoskeletal pain in the first community-based COPCORD study in Kuwait SUBJECTS AND METHODS: The validated Arabic version of the WHO-ILAR COPCORD Core Questionnaire was used in a survey of 2500 randomly selected Kuwaiti households to assess the frequency of musculoskeletal pain, disability, and health-seeking behavior in adult Kuwaitis. Those subjects reporting no musculoskeletal pain were identified and followed-up for a period of one year by contacting them every 2 weeks. Once a respondent reported pain, an appointment to report to hospital was offered and the subject was examined by a rheumatologist using American College of Rheumatology (ACR) criteria. RESULTS: Of 5159 adults who were non-complainers in an earlier prevalence phase of the study, 3341 responded to phone calls (response rate of 65%). The incidence of musculoskeletal pain was 6.6% (95% CI, 3.4%-9.7%) Age- and sex-adjusted incidence rates were 7.2% (95% CI, 3.4%-10.5%) for females and 6.1% (95% CI, 3.1%-9.2%) for males. The incidence rate increased with increasing age, body mass index, and with being married. The common sites of pain were knee, low back and shoulder. CONCLUSION: The incidence of musculoskeletal pain among Kuwaiti adults is reported for the first time. Further studies adopting the same instrument in other communities are warranted to compare with our findings.

Reference ranges of copper and zinc and the prevalence of their deficiencies in an Arab population aged 15-80 years.

Serum concentrations of copper and zinc were measured by flame atomic absorption spectrophotometry in 560 Kuwaitis aged from 15 to 80 yr who were in apparent good health to establish reference ranges and determine the prevalence of the deficiency of the trace metals. Zinc/copper ratios were derived by calculation. Because the mean +/- SD (microM) for copper in females (24.9 +/- 7) was significantly higher (p<0.0001) than in males (21.0 +/- 5.8) and vice versa for zinc (17.0 +/- 3.5 [males] vs 15.5 +/- 3.4 [females]) and zinc/copper ratios (0.87 +/- 0.28 [males] vs 0.67 +/- 0.27 [females]), gender-specific reference ranges were established in addition to reference ranges for the total population. The reference range for zinc was closer to those reported for other populations than was copper. Body mass index (BMI) and copper values were lower and the zinc/copper ratio was higher in the young (15-24 yr) compared to the older subjects. Copper concentrations were positively associated with BMI values (r=0.302, p<0.0001). Smokers had significantly lower (p=0.011) BMI than nonsmokers. The prevalence of copper and zinc deficiency, 0.36% and 0.53%, respectively, was low. Generally, the values for serum copper and zinc obtained for the Kuwaiti population studied suggest adequate dietary intake of the trace metals.

Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population.

Leptin, the obesity gene protein product, is a hormone with multiple physiological functions in the human. However, there are few reports in the literature on its role in trace element metabolism in the normal population. Therefore, we investigated the association among serum leptin, zinc, copper, and zinc/copper ratio in 570 healthy men and women aged 15 yr and older. Serum leptin assay was done with a commercial enzymelinked immunosorbent assay kit; serum zinc and copper levels were measured by an atomic absorption spectrophotometer. Serum leptin was found to be positively associated with age (r=0.254, p<0.001), sex (r=0.406, p<0.001), body mass index (BMI) (r=0.553, p<0.001), and serum copper (r=0.419, p<0.001), but negatively associated with the zinc/copper ratio (r=-0.423, p<0.001). There was no significant association between serum leptin and zinc (r= -0.131, p>0.05). When the confounding effects of age, sex, and BMI were removed, serum leptin was still positively associated with serum copper (r=0.197, p=0.02) and the serum zinc/copper ratio (r=-0.182, p=0.03). These results suggest that copper and not zinc has an effect on serum leptin levels.

Serum microminerals and the indices of lipid metabolism in an apparently healthy population.

Serum copper and zinc concentrations were measured in 560 apparently healthy Kuwaitis (238 males and 322 females) aged 15-80 years to assess micromineral effect on the indices of lipid metabolism. Following the recommended guidelines of the European Atherosclerosis Society (EAS) and the National Cholesterol Education Program Expert Panel (NCEPEP), the incidence of dyslipidemia was assessed from enzymatic assay data of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations. Males had significantly lower TC (P=0.029) and HDL-C (P<0.0001) levels than females, while TG were significantly (P=0.023) lower in females. The prevalence of hypercholesterolemia, hypertriglyceridemia, elevated LDL-C, and low HDL-C levels were 35, 30, 22, and 13%, respectively. Copper did not correlate with zinc (r = -0.067, P = 0.135) but was positively associated with TC (r=0.196, P<0.0001), LDL-C (r=0.134, P = 0.003), TG (r = 0.092, P=0.039), and age (r=0.281, P<0.0001). It is concluded that unlike in animal studies, copper excess in humans is associated with hyperlipidemia and therefore will predispose to atherosclerosis.