Efficacy, quality of life, and treatment satisfaction: an indirect comparison of calcipotriol/betamethasone dipropionate cream versus foam for treatment of psoriasis.

OBJECTIVE: To assess how the use of calcipotriol and betamethasone dipropionate (Cal/BDP) cream impacted efficacy, patients' quality of life (QoL), and treatment satisfaction versus Cal/BDP foam. METHODS: Data from clinical trials of Cal/BDP cream and foam were analyzed, by applying the common anchor Cal/BDP gel. Efficacy was assessed by Physician Global Assessment (PGA) treatment success and ≥75% reduction in Psoriasis Area and Severity Index (PASI75 response); QoL by Dermatology Life Quality Index (DLQI); treatment satisfaction by Psoriasis Treatment Convenience Scale (PTCS) and Topical Product Usability Questionnaire (TPUQ). RESULTS: Treatment with Cal/BDP cream was on par with foam on PGA treatment success (risk ratio (RR) for Cal/BDP cream versus foam: 0.80; 95%CI: 0.56, 1.14; p = .21) and PASI75 response (RR for Cal/BDP cream vs. foam: 0.85; 95%CI: 0.64, 1.13; p = .27) when assessed at the treatment duration of 8 weeks for Cal/BDP cream and 4 weeks for Cal/BDP foam. Treatment with Cal/BDP cream was associated with significantly greater treatment satisfaction versus foam on the domains: overall treatment satisfaction (p = .01), "ease of application" (p < .001), "lack of greasiness" (p < .001), "moisturizing effect" (p = .01), and almost significantly greater improvement on the domain "easily incorporated into daily routine" (p = .07). Furthermore, there was a trend for greater DLQI improvement with cream versus foam when assessed at recommended treatment duration [mean difference (MD) for Cal/BDP cream vs. foam: -1.00; 95%CI: -2.20, 0.20; p = .10]. CONCLUSIONS: Indirect comparison analyses showed that Cal/BDP cream significantly improves treatment satisfaction and tends to improve QoL versus foam. Cal/BDP cream is on par with foam on efficacy.

Correlations of fatigue in Danish patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis.

OBJECTIVE: To describe fatigue in relation to disease-specific and socioeconomic factors and to test possible correlations between fatigue and work impairment, quality of life, pain, sleep, depression, and physical functioning in people with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: A questionnaire-based cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and patient-reported outcomes (PROs) from patients with RA, PsA and axSpA in Denmark. PRO scales included the FACIT-Fatigue sub-scale, Work Productivity and Activity Impairment scale (WPAI), EuroQol (EQ-5D), Medical Outcomes Study Sleep Scale (MOS), Major Depression Inventory (MDI), and Health Assessment Questionnaire (HAQ). Respondents were recruited via routine visits to the outpatient rheumatology clinic; information on diagnosis, treatment and disease activity was collected from medical journals by trained nurses. RESULTS: 487 patients participated in the study. Fatigue was more present in women, experienced patients, and patients who changed medication in the past 12 months, who were unemployed, who had less education, and who had lower household income. There was no statistically significant difference between mean fatigue in the three diagnostic groups (p = 0.08). Fatigue correlated with all included PROs (Pearson correlation coefficients, p<0.0001). Stratifying for diagnosis and adjusting for socioeconomic factors did not change the conclusion. CONCLUSION: In a stable, representative group of patients with RA, PsA and axSpA, we found significant correlations between fatigue and work impairment, quality of life, pain, sleep, depression and physical functioning. Fatigue cannot be perceived as a single problem, but rather as a symptom that affects broadly.

Societal costs of venous thromboembolism and subsequent major bleeding events: a national register-based study.

AIMS: Detailed evidence on the societal costs of venous thromboembolism (VTE), i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE), and of subsequent major bleeding events, e.g. intracranial and gastrointestinal bleedings, is limited. The objective was to estimate the average 3-year societal event costs attributable to VTE and subsequent major bleedings in Denmark. METHODS AND RESULTS: Based on nationwide Danish registers, each incident patient diagnosed with VTE in the period from 2004 to 2016 was identified and matched with four non-VTE patients by nearest-neighbour propensity score matching. For bleeding patients, the reference cohort was VTE patients without bleedings. Event costs in terms of VTE, DVT, PE, and major bleedings in VTE patients were measured by the 'difference-in-actual-cost' method within 3 years after the incidence. Societal costs included healthcare costs (primary care, hospital, and prescription medicine), municipality home care services, and production loss. The study population included 74 137 VTE incident patients (DVT: 43 099; PE: 31 038), and 4887 VTE patients with a major bleeding within 3 years from VTE diagnosis. The 3-year attributable societal VTE event costs were 40 024 EUR (DVT: 34 509 EUR; PE: 50 083 EUR) with 53% of these costs appearing in the first incident year. Similar results for major bleedings were 51 168 EUR with 46% of these costs appearing in the first incident year. CONCLUSION: The societal costs of VTE and subsequent major bleedings are substantial and ought to be considered. Estimated costs of events may be informative in evaluating the impact of preventive interventions targeting VTE and subsequent major bleedings.

Severity of fatigue in people with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis - Results of a cross-sectional study.

BACKGROUND: Despite improvements in treatment for rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (axSpA), several key unmet needs remain, such as fatigue. The objective of this study was to describe the severity of fatigue, disease characteristics and socioeconomic factors in people with RA, PsA and axSpA. METHODS: The study was designed as a cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and fatigue in people with RA, PsA and axSpA in Denmark. Respondents were consecutively recruited for the study over a six-month period in 2018 via routine visits to outpatient rheumatology clinics. Study nurses collected information on diagnosis, current disease-related treatment and disease activity from medical journals. People were invited to complete a questionnaire related to socioeconomic factors and containing the FACIT-Fatigue subscale. Descriptive statistics were analyzed using SAS. RESULTS: We invited 633 people to participate, and 488 (77%) completed the questionnaire. Women constituted 62% of respondents, and the mean age was 53.5 years. Respondents had on average been diagnosed between 11 and 15 years ago. Overall, 79% had no changes to their disease-related treatment during the past year, and the average disease activity as indicated by DAS28 for RA and PsA was 2.48 and 2.36, respectively, and BASDAI for axSpA was 28.40. Fatigue was present in all three diagnoses (mean: 34.31). The mean fatigue score varied from respondents answering that they suffered from no or little fatigue (mean: 45.48) to extreme fatigue (mean: 10.11). Analyses demonstrated that the respondents were not considerably different from nonrespondents, and the study population is considered representative compared with Danish RA and axSpA patients in the Danish National Rheumatology Registry, the DANBIO database. CONCLUSION: We found that the majority of the study population were fatigued (61%). They had low disease activity and few disease-related treatment changes.

Societal costs due to meningococcal disease: a national registry-based study.

PURPOSE: Limited detailed evidence exists on the societal costs of meningococcal disease. The objective of this study was to estimate the average 5-year societal cost of events attributable to meningococcal disease in Denmark. METHODS: The study was based on the nationwide Danish registries. Incident patients diagnosed with meningococcal disease were identified and each matched with two controls, using direct matching on age, gender, and level of education. Siblings constituted a secondary control population where one patient was matched with one sibling control without meningococcal disease. Costs related to health care in the primary and secondary sectors, prescription medicine, municipality home care services and costs of production loss, ie, estimated loss of yearly earnings, were included (1997-2015). RESULTS: The incidence of meningococcal disease fluctuated between 1980 and 2015. The average attributable societal costs were highest the first year after diagnosis, with costs equaling USD 18,920 per event in the primary study population (matched controls) and USD 16,169 in the secondary study population (sibling controls). Hospital admission costs accounted for 65% and production loss for 30%; however, having a lifetime perspective and including loss due to premature death further increase the costs of meningococcal disease events. CONCLUSION: The costs of meningococcal disease are substantial, and the estimated costs of event may be informative in evaluating the impact of preventive interventions targeting meningococcal disease.

Spinal pain and co-occurrence with stress and general well-being among young adolescents: a study within the Danish National Birth Cohort.

This study aims to describe the patterns in low back, mid back, and neck pain complaints in young adolescents from the Danish National Birth Cohort (DNBC) and to investigate the co-occurrence of spinal pain and stress and general well-being, respectively. Cross-sectional data from the 11-year follow-up of DNBC were used. As part of a web-based survey, a total of 45,371 young adolescents between 10 and 14 years old completed the Young Spine Questionnaire, the Stress in Children Questionnaire, and a one-item question on general well-being. Associations between spinal pain and, respectively, stress and general well-being were estimated by means of multiple logistic regression models. Almost one fifth of boys and one quarter of girls reported spinal pain. Compared with adolescents who reported no stress, adolescents reporting medium and high values of stress had odds ratios (OR) of 2.19 (95% CI 2.08-2.30) and 4.73 (95% CI 4.28-5.23), respectively, of reporting spinal pain (adjusted for age, gender, and maternal education). Adolescents who reported poor general well-being had an OR of 2.50 (95% CI 2.31-2.72) for reporting spinal pain compared to adolescents with good general well-being. CONCLUSION: Spinal pain is a common complaint among young adolescents and co-occurs with stress and poor general well-being. The mutual dependency between the factors remained to be explained. What is Known: • The prevalence of spinal pain increases rapidly during childhood and adolescence, but different measurement instruments result in great variation in the estimates of spinal pain in children and adolescents. • Some studies have shown that different psychosocial measures are associated with spinal pain in children and adolescents. What is New: • Spinal pain, as measured by the newly developed and validated Young Spine Questionnaire, is a common complaint in young adolescents aged 10-14 years. • Spinal pain in young adolescents co-occurs with stress and poor general well-being.

Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis.

BACKGROUND: The evidence on selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder is unclear. METHODS: Our objective was to conduct a systematic review assessing the effects of SSRIs versus placebo, 'active' placebo, or no intervention in adult participants with major depressive disorder. We searched for eligible randomised clinical trials in The Cochrane Library's CENTRAL, PubMed, EMBASE, PsycLIT, PsycINFO, Science Citation Index Expanded, clinical trial registers of Europe and USA, websites of pharmaceutical companies, the U.S. Food and Drug Administration (FDA), and the European Medicines Agency until January 2016. All data were extracted by at least two independent investigators. We used Cochrane systematic review methodology, Trial Sequential Analysis, and calculation of Bayes factor. An eight-step procedure was followed to assess if thresholds for statistical and clinical significance were crossed. Primary outcomes were reduction of depressive symptoms, remission, and adverse events. Secondary outcomes were suicides, suicide attempts, suicide ideation, and quality of life. RESULTS: A total of 131 randomised placebo-controlled trials enrolling a total of 27,422 participants were included. None of the trials used 'active' placebo or no intervention as control intervention. All trials had high risk of bias. SSRIs significantly reduced the Hamilton Depression Rating Scale (HDRS) at end of treatment (mean difference -1.94 HDRS points; 95% CI -2.50 to -1.37; P < 0.00001; 49 trials; Trial Sequential Analysis-adjusted CI -2.70 to -1.18); Bayes factor below predefined threshold (2.01*10-23). The effect estimate, however, was below our predefined threshold for clinical significance of 3 HDRS points. SSRIs significantly decreased the risk of no remission (RR 0.88; 95% CI 0.84 to 0.91; P < 0.00001; 34 trials; Trial Sequential Analysis adjusted CI 0.83 to 0.92); Bayes factor (1426.81) did not confirm the effect). SSRIs significantly increased the risks of serious adverse events (OR 1.37; 95% CI 1.08 to 1.75; P = 0.009; 44 trials; Trial Sequential Analysis-adjusted CI 1.03 to 1.89). This corresponds to 31/1000 SSRI participants will experience a serious adverse event compared with 22/1000 control participants. SSRIs also significantly increased the number of non-serious adverse events. There were almost no data on suicidal behaviour, quality of life, and long-term effects. CONCLUSIONS: SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013004420.