The Effects of Brief Guided Imagery on Patients Suffering From Chronic Back Pain: An A-B Design Study.

BACKGROUND: Guided imagery (GI) is a non-pharmacological method used to reduce pain, stress, and anxiety. AIMS: This study aimed to evaluate the impact of brief GI on symptoms of chronic back pain in adults treated in the Rheumatology clinic. DESIGN: A-B design study. SETTINGS & PARTICIPANTS: A sample of 35 women with chronic back pain were recruited at the Rheumatology Outpatient Clinic of Barzilai Medical Center in Ashkelon, Israel. METHODS: All subjects completed questionnaires at recruitment (T1), and after 8-10 weeks, they completed questionnaires again before the first intervention (T2). The intervention included five brief GI group meetings every 2-3 weeks, one hour each (3-5 subjects per group). Participants learned 6 GI exercises and were asked to practice brief guided imagery exercises at least once daily. Then, questionnaires were completed the third time (T3). OUTCOME MEASURES: MOQ - Modified Oswestry Low Back Pain Disability Questionnaire, STAI - State-Trait Anxiety Inventory, FABQ - Fear-Avoidance Beliefs Questionnaire, NPRS - Numerical Pain Rating Scale (average pain over the last week). RESULTS: Compared with the period without intervention, NPRS (Δ = 2.53, standard error [SE] = 0.43, p < .001), STAI (Δ = 8.41, SE = 1.95, p < .001), and MOQ (Δ = 0.06, SE = 0.02, p = .019) reported significantly lower levels after brief guided imagery training. However, no statistically significant change was found in FABQ. CONCLUSIONS: The brief guided imagery intervention may help alleviate chronic back pain, help decrease anxiety, and improve daily activity in women who suffer from chronic low back pain.

Secukinumab real world drug retention compared to TNF-alpha inhibitors in psoriatic arthritis.

OBJECTIVES: To prospectively study real-world efficacy and safety of secukinumab in psoriatic arthritis (PsA) patients from the Israeli registry of inflammatory diseases. METHODS: PsA patients fulfilling the CASPAR criteria were included in the analysis from 2010 to 2019. The primary endpoint was secukinumab drug retention compared to other TNF-α inhibitors (TNFi). Bivariate and multivariate analyses were made by Cox regression analysis. Drug retention according to treatment line was examined with Kaplan-Meier curves. RESULTS: Included were 404 PsA patients who had 709 treatment courses during the study period. Ninety patients had been treated with secukinumab (22%). The secukinumab-treated patients were significantly older and their disease duration was longer. Secukinumab was less likely to be the first line of treatment compared to TNFi. Secukinumab had a drug retention comparable to TNFi, and a better drug retention than TNFi among biologic-experienced patients. Neither methotrexate combination nor body mass index affected the inefficacy event rate. Secukinumab had a similar rate of adverse events as TNFi. CONCLUSIONS: This multicentre real-world study demonstrated that secukinumab had a drug retention comparable to TNFi. Secukinumab had a better drug retention than TNFi among biologic-experienced patients. IL-17 inhibition is an effective mechanism of action to treat PsA in real life.

Real-world effectiveness of tofacitinib in patients with rheumatoid arthritis: a prospective observational study.

OBJECTIVES: Tofacitinib is an approved treatment for rheumatoid arthritis (RA), but data on its use in the "real-world" are limited. We sought to analyse tofacitinib drug survival in the Israeli registry and compare it to other biologic agents. METHODS: We included RA patients treated with tofacitinib, etanercept, golimumab, tocilizumab, or abatacept between 2010-2019. The primary endpoint was event-free survival (EFS), defined as the time from treatment initiation to a treatment failure event from any cause (i.e., inefficacy or intolerability). EFS was compared between agents using Cox regression and Kaplan-Meier analysis, stratifying patients by treatment line. RESULTS: A total of 964 eligible treatment courses were included (tocilizumab [325], etanercept [284], abatacept [127], tofacitinib [139], and golimumab [109]). In a univariate analysis, EFS with tofacitinib in the complete cohort was similar to etanercept, golimumab, and abatacept but was lower than tocilizumab) 3-year EFS 43% vs. 53%, HR 0.65). In a multivariable analysis, tofacitinib was similar to all other drugs, except for etanercept, which was inferior (HR 1.70); advanced treatment line was also associated with greater risk for failure (HR 1.64). In a univariable analysis stratified by the treatment line, tofacitinib had similar or better drug survival than other agents in the first and second lines. In the third line and beyond, tocilizumab had a higher EFS compared to tofacitinib (HR 0.57). CONLUSIONS: Drug survival with tofacitinib is related to treatment line. Early introduction is associated with similar or better survival than other agents, whereas tocilizumab was superior in the third line or later.

Scientific Productivity in Rheumatology Among Countries of the Organisation for Economic Co-operation and Development and Its Correlation to National Economic Indicators.

BACKGROUND: The purpose of this study was to examine the correlation between research productivity in the field of rheumatology and various updated economic indicators of Countries of the Organisation for Economic Co-operation and Development (OECD). METHODS: The number of documents published, number of citable documents, number of citations, citations per document, and the H-index for the 36 OECD countries in the field of rheumatology between 1996 and 2017 were obtained from the The Scimago Journal and Country rank source. The recent data regarding gross domestic product (GDP) per capita, total health spending as percent of GDP, and the gross domestic expenditure on research and development as percent of GDP were collected from the World Bank, OECD, and United Nations Educational, Scientific, and Cultural Organization Web sites, accordingly. The relationship between economic indicators and scientific productivity for each of the OECD countries was analyzed. RESULTS: A total of 132,314 documents were analyzed. A moderate to strong significance correlation was found between health expenditure and the number of documents published (r = 0.67, p < 0.001), number of citable documents (r = 0.68, p < 0.001), number of citation (r = 0.76, p < 0.001), and H-index (r = 0.77, p < 0.001). CONCLUSIONS: This study provides a current highlight on the relationship between academic productivity in rheumatology and economic indicators of OECD countries. We showed a positive moderate to strong significant correlation between total health expenditure as percent of GDP and different bibliometric indicators, implying another possible advantage of national investment in this filed.

Psychologic Morbidity Among Psoriatic Arthritis Patients in Remission or With Low Disease Activity: A Comparison Between Biologic and Conventional Synthetic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: The aim of this study was to compare the effect of biologic agents and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on the psychologic status of patients with psoriatic arthritis (PsA) in remission or with low disease activity. METHODS: This is a case-control study of PsA patients in remission or with low disease activity treated at a single-center combined rheumatologic-dermatologic clinic between 2015 and 2017. Patients were assigned to 2 comparison groups according to their treatment (1) biologic drugs and (2) csDMARDs therapy. Psoriatic arthritis disease activity was evaluated by disease activity score-28. Anxiety, somatization, and depression were evaluated by patient health questionnaires (PHQ): generalized anxiety disorder-7, PHQ-15, and PHQ-9, respectively. Disability was assessed by the health assessment questionnaire disability index (HAQ-DI). RESULTS: Thirty PsA patients on biologic treatment (BT) and 14 PsA patients in csDMARDs were enrolled. No significant differences in disease duration and treatment duration between the 2 groups were found. Disease activity score-28 was significantly better in the BT group compared with the csDMARDs group (1.8 ± 0.4 vs 2.1 ± 0.4, respectively, p = 0.028). A nonsignificant tendency toward higher scores in psychologic questionnaires was seen among the non-BT group. Moderate to high correlations between all mental questionnaires and HAQ-DI were found in both groups (0.567 ≤ r ≤ 0.850, p < 0.05). Patients with mental disturbance (generalized anxiety disorder-7/PHQ-15/PHQ-9 ≥ 5) showed significant poorer performance in their HAQ-DI in comparison with patient without physiological comorbidities in both groups. CONCLUSIONS: Tight disease control in PsA patients, achieved with BT, may offer an improvement in psychological outcomes in addition to relieving clinical symptoms.

Effect of Tocilizumab on Fatigue and Bone Mineral Density in Patients with Rheumatoid Arthritis.

BACKGROUND: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients. OBJECTIVES: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. METHODS: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. RESULTS: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data. CONCLUSIONS: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.

Comparison of two referral strategies for diagnosis of axial spondyloarthritis: the Recognising and Diagnosing Ankylosing Spondylitis Reliably (RADAR) study.

OBJECTIVE: To determine which of two referral strategies, when used by referring physicians for patients with chronic back pain (CBP), is superior for diagnosing axial spondyloarthritis (SpA) by rheumatologists across several countries. METHODS: Primary care referral sites in 16 countries were randomised (1 : 1) to refer patients with CBP lasting >3 months and onset before age 45 years to a rheumatologist using either strategy 1 (any of inflammatory back pain (IBP), HLA-B27 or sacroiliitis on imaging) or strategy 2 (two of the following: IBP, HLA-B27, sacroiliitis, family history of axial SpA, good response to non-steroidal anti-inflammatory drugs, extra-articular manifestations). The rheumatologist established the diagnosis. The primary analysis compared the proportion of patients diagnosed with definite axial SpA by referral strategy. RESULTS: Patients (N=1072) were referred by 278 sites to 64 rheumatologists: 504 patients by strategy 1 and 568 patients by strategy 2. Axial SpA was diagnosed in 35.6% and 39.8% of patients referred by these respective strategies (between-group difference 4.40%; 95% CI -7.09% to 15.89%; p=0.447). IBP was the most frequently used referral criterion (94.7% of cases), showing high concordance (85.4%) with rheumatologists' assessments, and having sensitivity and a negative predictive value of >85% but a positive predictive value and specificity of <50%. Combining IBP with other criteria (eg, sacroiliitis, HLA-B27) increased the likelihood for diagnosing axial SpA. CONCLUSIONS: A referral strategy based on three criteria leads to a diagnosis of axial SpA in approximately 35% of patients with CBP and is applicable across countries and geographical locales with presumably different levels of expertise in axial SpA.

Global Academic Productivity in the Field of Internal Medicine and Its Correlation to National Economic Indicators: A Bibliometric Analysis of 24 Years.

BACKGROUND: Previous studies have demonstrated a correlation between national economic indicators and academic productivity. However, such a relationship has not been studied in the field of internal medicine (IM). METHODS: The number of documents published, number of citable documents, number of citations, citations per document and the h index between 1996 and 2019 in the field of IM among the Organisation for Economic Co-operation and Development (OECD) countries were analysed. Data were derived from the The Scimago Journal and Country rank source. We analysed the correlation between these indicators to the gross domestic product (GDP) per capita, health spending as percent of GDP and gross domestic expenditure on research and development as percent of GDP (GERD). Economic data were collected from the OECD websites. RESULTS: A significant correlation was found between health expenditure and h index (r = 0.75, P < 0.001), number of citations (r = 0.72, P < 0.001), number of documents (r = 0.62, P < 0.001) and number of citable documents (r = 0.61, P < 0.001); between GERD and number of citations (r = 0.6, P < 0.001), h index (r = 0.6, P < 0.001), number of documents published (r = 0.53, P = 0.001) and citable documents (r = 0.51, P = 0.001); between the GDP per capita and number of citations (r = 0.46, P = 0.005), citations per document (r = 0.54, P = 0.001) and h index (r = 0.5, P = 0.002). CONCLUSIONS: This study demonstrated a positive correlation between academic productivity in the field of IM and economic indicators of the OECD countries, mainly health expenditure, implying the advantage of domestic investment in health.

High Body Mass Index is Associated with Shorter Retention of Tumor Necrosis Factor-Alpha Blocker Treatment in Rheumatoid Arthritis.

PURPOSE: To evaluate the association between body mass index (BMI) and tumor necrosis factor α (TNF-α) blockers retention in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: This prospective cohort study analyzed data about patients with RA who initiated TNF blockers from the Israeli registry of inflammatory diseases from 2011 to 2019. Patients were grouped by BMI: normal (BMI <24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), obese (BMI 30-34.9 kg/m2) and morbid obese (BMI ≥35 kg/m2). Treatment cessation due to inefficacy was defined as an "event" and therapy with a drug above 3 months was defined as a "course." Kaplan-Meier survival curve was used to describe drug survival. Event-free survival was calculated using Cox regression with a hazard ratio and confidence interval of 95%. RESULTS: The final analysis included 521 RA patients (80% females) treated with etanercept, infliximab, adalimumab or golimumab. Eight hundred and eighteen treatment initiations were included in the final analysis, 334 (41%) in the normal weight group, 261 (32%) in the overweight, 144 (17%) in the obese and 79 (10%) in the morbid obesity group. Three hundred and twenty-six (40%) treatment initiations were with etanercept, 215 (26%) with adalimumab 197 (24%) with infliximab, and 80 (10%) with golimumab. BMI was inversely associated with drug survival. Morbid obese patients were more likely to discontinue treatment compared with normal weight patients HR 2.28 (95% CI 1.67-3.10, p<0.01). This association remained significant for each drug type (except for golimumab) in a subgroup analysis. Adalimumab switch rate was higher compared to etanercept with HR =1.51 (95% CI 1.20-1.91, p<0.01), no other significant differences were noted between the other drugs. CONCLUSION: Morbid obese RA patients have lower TNF-α blocker retention compared to normal weight patients.

Treat-to-target concept implementation for evaluating rheumatoid arthritis patients in daily practice.

OBJECTIVE: We aimed to assess the implementation of the treat-to-target (T2T) concept in rheumatoid arthritis (RA) patients in daily practice. METHODS: All RA patients visiting one of the 7 academic medical centers in Israel in June 2015 with at least 3 previous clinic visits were included in this study. A common questionnaire was used to collect data from patients' medical records, and two independent rheumatologists evaluated the collected data for the implementation of the T2T concept. The associations between T2T implementation and the categorical and continuous variables were assessed. RESULTS: The study included 724 patients with a mean (standard deviation) age of 62.6 (13.97) years and 575 (80.4%) of them were women. Four centers used more than one scoring method, with Disease Activity Score-28 and Clinical Disease Activity Index) being most commonly used. Only 276 (38.1%) patients had disease score results in ≥3 visits, and the T2T recommendations were implemented for 245 (33.8%) of the 724 patients. The rate of implementation was higher in younger (p=0.028) rheumatoid factor-positive patients (p=0.011) and varied between centers (11.1%-87% p<0.0001). T2T implementation did not correlate to gender, place of residence, education, tobacco use, treatment regimens, and presence of erosions or comorbidities. CONCLUSION: The T2T concept was implemented on only 33.8% of patients and was not affected by RA disease severity. Further studies are needed to determine the reasons for this deviation from the T2T standard of care for RA as well as its consequences.

The Effect of Prednisone on Tuberculin Skin Test Reaction in Patients with Rheumatoid Arthritis.

OBJECTIVES: To assess the correlation between prednisone and methotrexate (MTX) treatment duration and dosage with the TST induration diameter of the TST reaction among rheumatoid arthritis (RA) patients. METHOD: We retrospectively analyzed consecutive cases of RA patients who were TNF-i therapy candidates. TST measurements, prednisone and methotrexate dosages, and treatment durations were recorded. A control group was randomly selected from healthy subjects. We compared TST reaction size between the following three groups: RA patients with current prednisone treatment, RA prednisone naïve patients, and healthy individuals. RESULTS: Our study sample comprised 43 RA patients with prednisone treatment, 22 prednisone naïve patients, and 195 healthy subjects. There was no significant difference in mean TST between the groups (5.3±6.6, 7.8±6.2, and 7.6±7.0, respectively, p=0.149). No correlation was noted between TST size and prednisone u-y (r=0.229, p=0.140) or methotrexate u-y in patients with and without prednisone therapy (r=0.219, p=0.158; and r=-0.293, p=0.186, respectively). CONCLUSIONS: Our results show that the TST reaction size among RA patients may not be affected by prednisone therapy. In addition, the TST reaction of RA patients may present similarly to that of healthy individuals. Therefore, we suggest that the criterion of a TST reaction of 5 mm to define latent TB infection in our population should be reevaluated.

Efficacy and survival of golimumab with and without methotrexate in patients with psoriatic arthritis: A retrospective study from daily clinical practice.

Golimumab is a recombinant human monoclonal antibody targeted against tumour necrosis factor-alpha (TNF-α). Golimumab is effective in the management of patients with active psoriatic arthritis (PsA). The aim of this study is to evaluate the clinical efficacy and survival of golimumab monotherapy versus co-administration with methotrexate (MTX) in patients with PsA in the clinical practice. This retrospective observational trial included patients with PsA. Efficacy was assessed by disease activity scores - DAS28, BASDAI, physician global assessment of disease (PGA) and CRP. Golimumab survival rate was estimated using the Kaplan-Meier analysis and univariate and multivariate Cox regression models. Forty-one patients with PsA were recruited; 26 patients were treated with golimumab, whereas 15 patients received combination therapy with MTX. The treatment resulted in significantly improved clinical measures of disease activity in comparison with baseline, including DAS28 CRP (4.1 vs 2.6, p ≤ 0.0001) and BASDAI (5.6 vs 3.8, p ≤ 0.001). Overall, 29 (71%) patients continued golimumab treatment (18 patients on monotherapy and 11 on combination therapy). The difference in the duration of golimumab survival between the combination therapy and monotherapy groups was not statistically significant (12.5 vs 12 months, p = 0.2). Similar efficacy profiles and survival rates were documented in patients with PsA regardless of the co-administration of methotrexate.

Readmissions to hospital within 30 days of discharge from the internal medicine wards in southern Israel.

INTRODUCTION: Hospital readmission within a short time of discharge is a common phenomenon in internal medicine. Although there are a few reports of intensive care and surgical readmission rates there is almost no information available on the readmission rates of internal medicine patients. AIMS: To explore the medical patient readmission rate within 30 days of discharge from a medical center in southern Israel, and determine how it may be related to age, gender, diagnoses and other factors. METHODS: Chart review of all 2469 patients admitted to the departments of internal medicine of Barzilai Health Center between May 1st and July 15th 2002. A randomized control group of 87 patients was gathered from patients admitted to hospital during the study period but who were not readmitted within 30 days of discharge. RESULTS: 124 patients (5%) were readmitted. They were significantly older than controls (mean age 68.7+/-14.8 vs. 59.3+/-16.3 years), (p<0.0003), 21% being over 80 years of age (compared with 9% of controls, p<0.05) and had a lower average Functional Independence Measure (FIM). The index hospitalization of readmitted patients was significantly longer than the hospitalization of control patients (6.1+/-5.5 vs. 4.1+/-3.8 days), (p<0.04). Most patients (85%) were readmitted for the same medical reason that prompted the original hospitalization. The 15% readmitted for other reasons were older (74.9+/-12.4 vs. 67.6+/-15.0 years) (p<0.001) and had a lower Functional Independence Measure (mean FIM 4.6+/-2.2 vs. 5.7+/-1.9), (p<0.05). New immigrants (mean age 71.1+/- 12.9 years) had significantly lower readmission rate compared to the general population (3.2% vs. 4.98%), (p<0.05). Veteran Israelis, on the other hand, had a higher readmission rate than the general population (6.8% vs. 4.98%) (p<0.001). CONCLUSION: Only 5% of patients required readmission. The original hospitalization period of readmitted patients was significantly longer than controls and most readmissions were for the original medical problem for which they were readmitted originally or because of a low functional status. Hospitalized new immigrants although being older in age are less likely to require readmission, while veteran Israelis are more likely to be readmitted.

Rituximab-related late-onset neutropenia in patients with rheumatic diseases: successful re-challenge of the treatment.

BACKGROUND: We describe here 2 patients who developed late-onset neutropenia after Rituximab treatment. While this phenomenon is well described among patients suffering from hematological malignancies, such adverse effects are rare among patients with rheumatic diseases. CASE REPORT: Two patients, the first with rheumatoid arthritis and the second with granulomatosis with polyangiitis, were treated by Rituximab after all previous treatments failed. The patients developed late-onset neutropenia after several courses of treatment. The first patient, with symptomatic neutropenia, recovered after a single dose of granulocyte macrophage stimulating factor, and the second patient's neutrophils increased spontaneously. Both patients were retreated by rituximab in their scheduled time without further complications. CONCLUSIONS: Our case series is unique because the same phenomenon appeared in patients with different rheumatic diseases. This case series confirms the possibility of continuing the treatment without further adverse effects.

[Splenic abscess as an unusual manifestation of colonic carcinoma].

A patient was admitted to the Internal Medicine Department after suffering from fever for 4 days. A splenic abscess was found in an ultrasound examination and was confirmed by an abdominal computerized tomography and galium scan. Antibiotic treatment was successful, however barium enema was performed due to the lack of a predisposing factor for this unusual abscess. A polypoid mass was found in the splenic flexure of the colon. Colonoscopy and histologic examination confirmed the mass to be colonic adenocarcinoma. Either an endoscopic examination or barium enema are recommended to exclude colonic lesions in cases of splenic abscess without an obvious cause.

[Nosocomial infections in internal medicine departments].

BACKGROUND: Nosocomial infections are a major cause of morbidity and mortality among hospitalized patients. The use of new generation antibiotics of wide spectrum caused a higher rate of virulent infections. AIMS: a) To study the prevalence, pattern and etiology of nosocomial infections in patients hospitalized in departments of internal medicine. b) to determine the characteristics of high-risk patients, deserving special precautions. METHODS: All medical files of patients who were admitted to internal medicine departments during the years 1994-8 were reviewed. All patients with nosocomial infections were included according to specific criteria. RESULTS: Of 2789 medical files, 72 (2.6%) patients, randomly elected had 76 episodes of nosocomial infection. Urinary tract infection (40.8%), pneumonia (32.9%) and sepsis (9.2%) were the most frequent infections. Mortality was significantly higher in patients with nosocomial infections--48.6% compared to 5% in a control group (p < 0.001). E. Coli, Pseudomonas auroginosa, and Staphylococcus Aureus were the most frequent infecting bacteria. Empiric antibiotic therapy was used in 84.7% of the patients. Any bacterial isolation was found in 61.9% of the patients samples (including blood cultures, urine cultures etc). Old age, female gender, prolonged hospitalization, mechanical ventilation and indwelling urinary catheter were found as risk factors for nosocomial infections. CONCLUSIONS: 1. Nosocomial infections in internal medicine departments in Brazilai hospital were found to be less common than previously reported. 2. Five risk factors for nosocomial infections were correlated with a higher prevalence of the disease. 3. Mortality due to nosocomial infections is very common, probably due to inappropriate empiric treatment and high rate of bacterial resistance. 4. Simple preventive measures as well as immediate treatment of nosocomial infection with proper antibiotics are expected to decrease mortality.

Appearance of ANCA - associated vasculitis under Tumor necrosis factor-alpha inhibitors treatment.

BACKGROUND: Tumor necrosis factor-alpha inhibitors treatment is accosiated with several side effects. The most common are injection side reactions, headache, nausea and infections. The more rare are development of systemic autoimmune diseases. CASE REPORT: We describe two patients, who developed ANCA associated vasculitis during Tumor necrosis factor alpha inhibitors treatment. The diagnosis was confirmed by appropriate tissue picture, CT scan and laboratory findings. CONCLUSIONS: Our case series are unique, because vasculitis appeared after many years of the treatment and during complete patient's remission of there main illness.

Simultaneous Breast Cancer and Kaposi's Sarcoma Complicating Rheumatoid Arthritis.

For a number of years we have been following the medical literature to find a relationship between chronic treatment with methotrexate and breast cancer occurrence, because we had had in our clinic a female patient who had had two consecutive cancers following methotrexate treatment for rheumatoid arthritis (RA). We were much surprised to find in some papers that breast cancer incidence is low in women with RA. Since then, we have found several papers explaining the low incidence of breast cancer among women being under NSAIDs, but those papers are not univocal. Methotrexate is a known antifolate agent and it has been demonstrated that dietary shortage of folate is a risk factor for breast cancer development.