Predictors at diagnosis for start of biologic disease-modifying antirheumatic drugs in patients with early rheumatoid arthritis: a cohort study.

OBJECTIVES: To investigate the relation between patient characteristics at rheumatoid arthritis (RA) diagnosis and subsequent initiation of treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs). DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: Consecutive patients (N=330) with early RA (symptom duration <12 months) diagnosed at Skåne University Hospital, Malmö/Lund, Sweden, from 2012 to 2016, were included. Data on demographics, education, comorbidities and treatment were obtained from national registers. OUTCOME: The relation between patient characteristics at diagnosis and time to first bDMARD/tsDMARD initiation was analysed using Cox regression models. As a secondary outcome, the relation between characteristics at diagnosis and b/tsDMARD initiation within 3 years was analysed using logistic regression. RESULTS: A total of 330 patients (mean age 59.2 years; SD 16.4) were included. During follow-up, 41% received a bDMARD (never preceded by a tsDMARD). Higher age at diagnosis was associated with a lower probability of starting bDMARD treatment (multivariable-adjusted HR 0.66 per SD; 95% CI 0.56 to 0.78). Anticitrullinated protein antibody (ACPA) positivity and higher tender joint count at diagnosis were also associated with subsequent bDMARD treatment initiation in multivariable analysis. A higher level of formal education and absence of comorbidities predicted start of a bDMARD in crude, but not in age-adjusted, analyses. CONCLUSIONS: Older patients with RA were less likely to start bDMARDs, whereas ACPA-positive patients, and those with extensive joint involvement at diagnosis, were more likely to receive early bDMARD treatment. The impact of age on the subsequent start of bDMARD therapy was not explained by level of education or comorbidities, suggesting that other aspects of age influence treatment decisions in early RA.

Rituximab in clinical practice: dosage, drug adherence, Ig levels, infections, and drug antibodies.

The objective of this study is to explore the following: (1) the impact of two different initial doses and cumulative 2-year dose of rituximab (RTX) on drug adherence and predictors of adherence to treatment in rheumatoid arthritis (RA) patients in an observational clinical setting, (2) immunoglobulin levels (IgG/IgM/IgA) during repeated treatment and their relation to infections, and (3) development of anti-rituximab antibodies (ADA). All RA patients receiving RTX from January 2003 to April 2012 at the department were included. The initiating doses were 500 or 1000 mg intravenously days 1 and 15. Drug adherence was estimated using life-table. Baseline predictors of adherence to treatment were analyzed using Cox regression model. Levels of immunoglobulins were measured at treatment initiation and before retreatment. Serum levels of RTX and ADA were measured in 96 patients at 6 months using ELISA. One hundred fifty-three patients were included. Seventy-four (48%) started treatment with 500 and 79 (52%) with 1000 mg. No difference in drug adherence was seen between the different initial or cumulative RTX doses. Methotrexate (MTX) use and low DAS28 at baseline predicted better drug adherence. Ig levels decreased with repeated treatments but low levels were not associated with infections. 11/96 patients had developed ADA at 6 months. Long-term adherence to RTX in RA patient was not influenced by starting- or cumulative 2-year doses. MTX use and low DAS28 at baseline was positively associated with drug adherence. Decreasing Ig levels during treatment were not associated with risk of infections. Development of ADA may influence treatment efficacy and tolerability.

Sustained Remission Improves Physical Function in Patients with Established Rheumatoid Arthritis, and Should Be a Treatment Goal: A Prospective Observational Cohort Study from Southern Sweden.

OBJECTIVE: It has been proposed that remission should be maintained throughout the course of rheumatoid arthritis (RA); however, the evidence supporting this is limited. Physical function measured by the Health Assessment Questionnaire (HAQ) is a major outcome in RA, and HAQ is shown to be one of the strongest predictors of longterm outcomes. The purpose of this study was to investigate the physical function over a long time in patients with RA who achieved sustained remission (SR) compared with that of patients occasionally achieving remission [non-sustained remission (NSR)]. METHODS: Patients with RA treated with antitumor necrosis factor and included in the South Swedish Arthritis Treatment Group register were eligible for this study. We identified patients with a Disease Activity Score at 28 joints (DAS28) < 2.6 or Simplified Disease Activity Index (SDAI) ≤ 3.3 at some point and those who achieved SR, i.e., remission during consecutive visits for at least 6 months. The course of functional status was assessed using the HAQ at each visit. RESULTS: Of the 2416 patients, 1177 (48.7%) reached DAS28 remission at some point. SR was achieved by 382 (15.8%) for the DAS28 and 186 (7.7%) for the SDAI criteria. Comparing the SR and NSR groups, HAQ improved during the first 12 months in the DAS28 remission. HAQ continued to improve relatively as long as SR was maintained. A higher proportion of patients in SR reached full physical function. CONCLUSION: In patients with established RA, physical function measured by the HAQ improves in patients reaching SR compared with patients who only occasionally reach remission. The improvement continues while in remission, which supports that maintaining remission should be a treatment goal.

Sustained Remission in Tumor Necrosis Factor Inhibitor-treated Patients with Rheumatoid Arthritis: A Population-based Cohort Study.

OBJECTIVE: To study frequency, possible baseline predictors, timing, and duration of sustained remission [SR; defined as 28-joint Disease Activity Score (DAS28) < 2.6 for at least 6 mos] in patients with established rheumatoid arthritis (RA) treated with different tumor necrosis factor (TNF) inhibitors [etanercept (ETN), infliximab (IFX), adalimumab (ADA)]. In addition, the aim was to compare (head-to-head) the effectiveness of individual drugs in patients receiving their first anti-TNF treatment. METHODS: All anti-TNF-treated patients with RA included in the observational South Swedish Arthritis Group register were eligible. We identified the patients' first SR periods (time between first visit after treatment initiation with DAS28 < 2.6 and subsequent visit with DAS28 ≥ 2.6). Baseline predictors of SR in biologic-naive patients were studied using multivariate regression models. Remission duration and timing of remission start was estimated with Kaplan-Meier curves. RESULTS: Of the 2416 patients included, 382 (15.8%) fulfilled the criteria for SR. Median estimated duration of SR was 5.25 years. Predictors for SR were male sex, low Health Assessment Questionnaire, low DAS28, methotrexate (MTX) treatment, and the calendar year of treatment start. OR for achieving SR within the first 12 months of treatment were 1.86 for ETN (95% CI 1.33-2.61) compared to IFX. HR for 4 years of SR were 1.32 for ETN (95% CI 1.01-1.74) and 1.84 for ADA (95% CI 1.23-2.78), with IFX as the reference drug. CONCLUSION: SR was uncommon in patients with RA treated with anti-TNF in clinical practice. However, patients remained in SR for a substantial period of time. Concomitant MTX treatment predicts remission. ETN and ADA were more likely in reaching SR.

[Constrictive pericarditis with severe heart failure - a case report and review of the literature]. / Grefjagollurshús - sjúkratilfelli med umraedu.

Constricitve pericarditis is an uncommon condition, often of unknown etiology but can be caused by infections, such as tuberculosis, inflammation of the pericardium, radiation therapy or asbestos exposure. Constrictive pericarditis is characterized by fibrosis and often severe calcifications of the pericardial sac which eventually restricts normal diastolic filling of the heart. This consequently leads to a combination of left and right heart failure, often with prominent jugular venous distentsion, liver enlargement, peripheral edema and lethargy. Diagnosis can be difficult and is often delayed. Surgery, involving partial removal of the pericardial sac, usually leads to relief of symptoms. Here we report a case from Landspitali together with a review of the literature.

Middle lobe syndrome: a nationwide study on clinicopathological features and surgical treatment.

INTRODUCTION: Middle lobe syndrome (MLS) is a relatively uncommon lung disease that is characterized by damage to the middle lobe and often needs surgical intervention. OBJECTIVE: To study clinical, radiological and histological features of all patients who underwent surgical resection for MLS in Iceland over a 13-year period, including evaluation of surgical outcome. METHODS: Information on patients who underwent surgery of the right middle lobe in Iceland from 1984 to 2006 was obtained from a centralized diagnosis and pathology registry. Clinical data were collected retrospectively from clinical records from hospitals and from private offices. All pathology specimens were reviewed. RESULTS: We studied 18 patients, 3 males and 15 females between the ages 2 and 86 years (mean 55). The most common clinical features were recurrent infection (n = 15), chronic cough with productive sputum (n = 9), chest pain (n = 8) or dyspnea (n = 7). The most common findings on chest radiographs and on computerized tomography of the chest were atelectasis, consolidation and bronchiectasis. One patient had a foreign body. The most common major histological finding was bronchiectasis in nine patients, and two had foreign body reaction. Minor findings included bronchiolitis, organizing pneumonia and peribronchial inflammation. All patients survived surgery with minor peri- and postoperative complications. CONCLUSION: MLS is more common in females, and recurrent infections, chronic productive cough and dyspnea were the most common symptoms. Bronchiectasis is the most common histological finding. MLS can be treated effectively with lobectomy with low mortality and rate of complications.

[Attitudes and knowledge on sexual matters among 16-year old teenagers]. / Vidhorf og thekking 16 ára unglinga á kynlífstengdu efni.

OBJECTIVE: Sexually transmitted diseases and unplanned pregnancies are social and health issues among Icelandic teenagers and are more prevalent than in neighbouring countries. In 2001 knowledge and attitudes to sexual education, sexually transmitted disease and contraception among 16-year olds were investigated by questionnaire. Knowledge was defective. The study was repeated in 2005-2006 in a larger sample and change over five years estimated after an educational effort on sexual issues was launched by medical students (www.astradur.is). MATERIAL AND METHODS: A survey with 69 multiple choice questions was administered in conjunction with sexual education by medical students. Changes in replies to the same questions were compared between 2001 and 2005-2006 as well as before and after teaching. RESULTS: A total of 201 teenagers were in the first and 417 in the latter study. There was a wish for sexual education in schools and by outside advisers. The parental role was relatively small. Knowledge was inadequate in both, but significant improvement was seen between periods and after the educational effort (p<0.001). Misconceptions were common, such as 13% of boys believing that oral contraceptives protected against sexually transmitted disease, that herpes infection was curable by antibiotics (70% of respondents) and that modern medicine cured HIV (10% of respondents). Attitudes to sexual behavior had not changed by 2005-6 and 66% thought it normal for 14-16 year olds to have sexual intercourse, while only 8% were ready to handle the consequences. CONCLUSION: Misconception and inadequate knowledge on various key aspects of sexuality is common, not least on serious sexually transmitted diseases, which suggests a need for improved sexual education in late primary and early secondary school.