A value-based healthcare model for initiating and switching psoriasis therapies-Results from the prospective multicentre IMPROVE study.

BACKGROUND: Little is known about the therapeutic benefits of a value-based healthcare model compared to a traditional activity-based incentive model in psoriasis (PsO). OBJECTIVES: This prospective non-interventional study evaluated an outcome-based, patient-centred management model for patients with PsO. METHODS: In total, 49 patients with a Psoriasis Area and Severity Index (PASI) ≥3 who were starting or switching between treatments were included. Patients were assessed at baseline, 3 and 9 months. The patient benefit index (PBI) was calculated using predefined questionnaires. An expected PBI was calculated and adjusted for risk factors known to complicate treatment, that is overweight and smoking. The model remunerated the department on whether the observed PBI exceeded the expected PBI to incentivize over-performance. RESULTS: In total, 40 patients (80%) completed all three visits; 32.7% were smokers and 73.5% were overweight. Mean PASI at baseline was 11.5 (SD 9.1); PASI improved significantly from baseline through 3 months: mean reduction, 8.0 (SD 9.2), p < 0.001 and was maintained until 9 months: mean further reduction, 0.1 (SD 3.3), p = 0.893. The mean PBI was 2.5 (SD 1.3) and 2.8 (SD 1.1) at 3 and 9 months, respectively. A PBI ≥1 was achieved by 87.8% at 3 and 95.1% at 9 months. Overall, the department was remunerated a mean 2721.1 DKK (SD 4472.8) per patient. In subgroup analysis, the department was remunerated a mean of, respectively, 2428.6 (SD 5089.5), 2636.6 (SD 4471.3) and 3196.5 (SD 4497.1) DKK for patients with none, 1 or 2 risk factors, that is smoking or/and overweight. CONCLUSIONS: The model evaluated herein is the first value-based model to calculate remuneration from patient reported outcomes and showed to successfully predict the expected PBI and remunerate treatment based on whether the expected treatment goal was met or exceeded. This can be utilized in the patient-centred management of PsO.

ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe.

BACKGROUND: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship. DESIGN AND METHODS: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research. RESULTS: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care. CONCLUSIONS: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking.

HSP90 inhibitor RGRN-305 for oral treatment of plaque-type psoriasis: efficacy, safety and biomarker results in an open-label proof-of-concept study.

BACKGROUND: HSP90 is a downstream regulator of tumour necrosis factor (TNF)-α and interleukin (IL)-17A signalling and may therefore serve as a novel target in the treatment of psoriasis. OBJECTIVES: This phase Ib proof-of-concept study was undertaken to evaluate the safety and efficacy of a novel HSP90 inhibitor (RGRN-305) in the treatment of plaque psoriasis. METHODS: We conducted an open-label, single-arm, dose-selection, single-centre proof-of-concept study. Patients with plaque psoriasis were treated with 250 mg or 500 mg RGRN-305 daily for 12 weeks. Efficacy was evaluated clinically using the Psoriasis Area and Severity Index (PASI), body surface area (BSA), Physician's Global Assessment (PGA) scores and the Dermatology Life Quality Index (DLQI). Skin biopsies collected at baseline and at 4, 8 and 12 weeks after initiation of treatment were used for immunohistochemical staining and for gene expression analysis. Safety was monitored via laboratory tests, vital signs, electrocardiogram and physical examinations. RESULTS: Six of the 11 patients who completed the study responded to RGRN-305 with a PASI improvement between 71% and 94%, whereas five patients were considered nonresponders with a PASI response < 50%. No severe adverse events were reported. Four of seven patients treated with 500 mg RGRN-305 daily experienced a mild-to-moderate exanthematous drug-induced eruption owing to the study treatment. Two patients chose to discontinue the study because of this exanthematous eruption. RGRN-305 treatment resulted in pronounced inhibition of the IL-23, TNF-α and IL-17A signalling pathways and normalization of both histological changes and psoriatic lesion gene expression profiles in patients who responded to treatment. CONCLUSIONS: Treatment with RGRN-305 showed acceptable safety, especially in the low-dose group, and was associated with clinically meaningful improvement in a subset of patients with plaque psoriasis, indicating that HSP90 may serve as a novel future target in psoriasis treatment.

Early indicators of primary brain tumours: a population-based study with 10 years' follow-up.

BACKGROUND AND PURPOSE: To improve diagnoses of primary brain tumours, knowledge about early indicators is needed. Nationwide Danish health registries were used to conduct a population-based case-control study including all persons diagnosed with a primary brain tumour between 2005 and 2014 in Denmark. METHODS: All 5135 adults diagnosed with a primary brain tumour in the Danish Cancer Registry were matched to 19 572 general population comparisons from the Danish Civil Registration System. Conditional logistic regression analyses were applied to estimate age- and multivariable-adjusted odds ratios (ORs) for the occurrence of a primary brain tumour up to 10 years after hospital diagnoses or prescription of medications related to nervous system diseases and mental and behavioural disorders. RESULTS: Increased odds for primary brain tumour after nervous system diseases and mental and behavioural disorders manifested up to 10 years before tumour diagnosis were found. Increased odds were seen especially for hospital contacts for inflammatory nervous system diseases [OR 11.3; 95% confidence interval (CI) 6.5-19.7], epilepsy (OR 9.0; 95% CI 7.6-10.7) and antiepileptic medications (OR 3.6; 95% CI 3.2-4.0), whilst antidementia medications provided a strong, protective association for primary brain tumours (OR 0.5; 95% CI 0.3-0.8). CONCLUSIONS: Sub-groups of patients diagnosed with or being prescribed certain medications targeting nervous system diseases and mental and behavioural disorders may be at increased risk of being diagnosed with a primary brain tumour. Further studies should disentangle the potential underlying common pathogenetic pathways. The results are important for the development of systematic clinical approaches to ensure early diagnosis of primary brain tumours.

Feasibility and estimated efficacy of blood flow restricted training in female patients with rheumatoid arthritis: a randomized controlled pilot study.

Objectives: The study aimed to evaluate the feasibility of a blood flow restriction (BFR) training regimen in patients with rheumatoid arthritis (RA); and to compare the effects of 4 weeks of BFR training with low-intensity strength training on muscle strength, muscle endurance, and joint pain in patients with RA.Method: In this non-blinded pilot randomized controlled trial, 18 women with RA aged 18-65 years performed low-intensity strength training for the lower limbs three times a week for 4 weeks, and were randomized to train with or without occlusion bands. The primary outcomes were registration of the recruitment process, compliance with training sessions, side effects, perceived pain, and a satisfaction survey. The secondary outcomes were changes in muscle strength, muscle endurance, and joint pain.Results: The findings of this pilot study included a challenging recruitment process, well tolerated training and test protocols, overall good patient satisfaction, no serious side effects, and high compliance. Both groups achieved significant improvements in knee extensor strength from baseline to follow-up, with a change of 11.5 kg [interquartile range (IQR) 9.8;13.0] in the intervention group and 8.4 kg (IQR 5.5;12.4) in the control group, and a significant between-group difference in favour of the intervention group (p = 0.0342).Conclusions: The feasibility results of this study indicated a challenging recruitment process, general satisfaction with the BFR and exercises, good compliance, and only expected non-serious side effects. BFR training may improve knee extensor strength in women with RA, compared low-intensity strength training without BFR.

Correction to: Quality of life in bladder cancer patients receiving medical oncological treatment; a systematic review of the literature.

The original article contains a major error whereby a main Table is omitted. Thus, the following corrections to the original article should be considered.

Quality of life in bladder cancer patients receiving medical oncological treatment; a systematic review of the literature.

BACKGROUND: Previous quality of life (QoL) literature in bladder cancer (BC) patients has focused on finding the preferred urinary diversion while little is known about the QoL of patients in medical oncological treatment (MOT). We performed a systematic review to assess the existing literature on QoL in patients with muscle-invasive BC (MIBC) undergoing MOT. METHODS: A systematic search of Pubmed and Embase was performed. Inclusion criteria were studies containing QoL data for patients undergoing chemo- and/or radiotherapy. We extracted all QoL scorings at different time intervals and on the six most prevalent domains: overall QoL, urinary, bowel sexual symptoms, pain and fatigue. The study was carried out according to PRISMA guidelines for systematic reviews and GRADE was used to rate the quality of evidence from the included studies. RESULTS: Of 208 papers reviewed, 21 papers were included. Twenty-one different QoL instruments were applied. The only data on QoL during chemotherapy was from patients in clinical trials investigating new treatments. No studies were found for patients in neoadjuvant treatment. The level of evidence at each time point was graded as very low to moderate. From the studies included the overall QoL seemed inversely related to the organ-specific impairment from sexual and urinary symptoms and increased with decreasing organ-specific symptoms for long term survivors > 6 months after treatment. CONCLUSIONS: Collection of data on QoL from patients with MIBC disease undergoing MOT has been sparse and diverse. The present data can act as a summary but prompts for more prospective collection of QoL data from BC patients.

Does losing a parent early influence the education you obtain? A nationwide cohort study in Denmark.

BACKGROUND: Health inequalities are rooted in education and we investigate the association between early parental death and attainment across the educational spectrum. METHODS: Using total population data on Danes born between 1982 and 2000 (n = 1 043 813), we assess incidence rate ratios (RRs) by gender for attainment of each educational level (basic school, high school or vocational training, bachelor degree or professional programme, and university graduate degree) according to loss of a parent before the age of 18 years. We adjust for family income, education and psychiatric illness and examine parent's gender, cause of death and child's age at time of death as potential moderators. RESULTS: Bereaved people had significantly lower attainment rates than non-bereaved people: basic school (RR = 0.95; 95% CI: 0.93-0.97 for men and 0.96; 0.94-0.98 for women), high school or vocational training (0.78; 0.76-0.80 for men and 0.82; 0.80-0.84 for women), bachelor degree or professional programme (0.74; 0.70-0.79 for men and 0.83; 0.79-0.86 for women) and university graduate degree (0.77; 0.68-0.86 for men and 0.77; 0.69-0.86 for women). Parent's gender, cause of death and child's age at the death did not modify the associations. CONCLUSIONS: As education impacts population health, support for bereaved school children may be more important than realized.

The effect of an attachment-oriented couple intervention for breast cancer patients and partners in the early treatment phase: A randomised controlled trial.

OBJECTIVE: Patients and partners both cope individually and as a dyad with challenges related to a breast cancer diagnosis. The objective of this study was to evaluate the effect of a psychological attachment-oriented couple intervention for breast cancer patients and partners in the early treatment phase. METHODS: A randomised controlled trial including 198 recently diagnosed breast cancer patients and their partners. Couples were randomised to the Hand in Hand (HiH) intervention in addition to usual care or to usual care only. Self-report assessments were conducted for both patients and partners at baseline, postintervention (5 months), and follow-up (10 months), assessing cancer-related distress, symptoms of anxiety and depression, and dyadic adjustment. Patients' cancer-related distress was the primary outcome. RESULTS: Cancer-related distress decreased over time in both patients and partners, but the intervention did not significantly affect this decrease at postintervention (P = .08) or follow-up (P = .71). A significant positive effect was found on dyadic adjustment at follow-up for both patients (P = .04) and partners (P = .02). CONCLUSIONS: There was no significant effect of the HiH intervention cancer-related distress. The results suggest that most couples can cope with cancer-related distress in the context of usual care. However, the positive effect on dyadic adjustment implies that the HiH intervention benefitted both patients and partners. Future studies should investigate how to integrate a couple focus in usual cancer care to improve dyadic coping in the early treatment phase.

Tumour necrosis factor-α plays a significant role in the Aldara-induced skin inflammation in mice.

BACKGROUND: Recently, the Aldara-induced psoriasis-like skin inflammation model in mice has attracted increased attention, due to its dependence on the same immunological pathways and cell types as in human psoriasis. OBJECTIVES: To study the impact of constitutive deficiency of tumour necrosis factor (TNF)-α and its upstream regulator mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2, herein MK2) in the Aldara-induced psoriasis-like skin inflammation model. METHODS: TNF-α knockout (KO), MK2 KO and wild-type (WT) mice divided into separate groups received either 45-mg Aldara cream or control cream for 5 consecutive days. The skin inflammation was evaluated clinically, histologically, and by quantitative reverse transcription-polymerase chain reaction. RESULTS: We found that TNF-α KO mice developed significantly less skin inflammation compared with WT mice, as evaluated clinically and histologically. At the molecular level, we demonstrated that the Aldara-induced mRNA expression of the psoriasis-related inflammatory markers interleukin (IL)-17C, IL-23p19, IL-12p40, IL-17A, IL-22 and S100A8 was significantly decreased in TNF-α KO mice compared with WT mice. No significant difference in the mRNA expression of these inflammatory markers between MK2 KO mice and WT mice was found, although Aldara-treated MK2 KO mice showed a tendency towards a lower mRNA expression of IL-17A and IL-22 compared with WT mice. CONCLUSIONS: We were able to demonstrate significantly lower levels of inflammation in TNF-α KO mice compared with WT mice, supporting the use of this model in future studies characterizing the role of TNF-α in psoriasis.

Facilitation of school re-entry and peer acceptance of children with cancer: a review and meta-analysis of intervention studies.

Increased survival rates from childhood cancer call for efforts to reintegrate children with cancer back into their academic and social environments. The aims of this study were to: (1) review and analyse the existing literature on school re-entry interventions for children with cancer; and (2) discuss the importance of peer involvement in the treatment. Relevant databases were searched using equivalent search algorithms and six studies were selected that target children with cancer and/or their classmates. Two authors independently reviewed the literature for data extraction. The articles were reviewed using the PRISMA model for reporting reviews. Statistical calculations for the meta-analyses were done using Review Manager 5.2. The meta-analyses showed significant effects of school re-entry programmes in terms of enhancing academic achievement in children with cancer (P = 0.008) and lowering their levels of depression (P = 0.05). Increased knowledge among classmates was associated with less fear and a more positive attitude towards the child with cancer. Due to limited numbers of patients, lack of control groups, and the diversity of intervention strategies used in previous studies, there is a need for intervention programmes exploring the optimal path for the reintegration of children with cancer into the education system and into their peer groups.

TSLP, IL-31, IL-33 and sST2 are new biomarkers in endophenotypic profiling of adult and childhood atopic dermatitis.

BACKGROUND: Recent years have seen growing interest in identifying new biomarkers in atopic dermatitis (AD) that could serve as indicators of disease severity and predictors of treatment response. OBJECTIVES: We compared serum levels of thymic stromal lymphopoietin (TSLP), interleukin(IL)-31, IL-33 and soluble(s)ST2 in AD patients and healthy controls, investigated the possible correlation with disease severity, investigated if other atopic comorbidities could play a role, and assessed their potential as biomarkers in AD. METHODS: Using standard enzyme-linked immunosorbent assay techniques, we measured target serum levels in 71 adults and 61 children with AD, and 31 adult controls. We characterized our cohort by disease severity, radioallergosorbent test status concerning both dietary and inhalant allergens, and anamnestic reports of food allergy, concomitant allergic asthma and/or allergic rhinitis. RESULTS: Serum levels of TSLP, IL-31 and IL-33, but not sST2, were significantly elevated in AD patients compared with controls. In AD patients, both IL-31 and IL-33 serum levels were higher in children than in adults, while the opposite was the case for sST2. We observed no correlation between disease severity and any of the investigated targets. While serum TSLP levels were unaffected by concomitant allergies and atopic comorbidities, serum levels of IL-31, IL-33 and sST2 were affected to a small extent. We found a positive correlation between TSLP, IL-31 and IL-33, and an inverse relationship between IL-33 and sST2. CONCLUSIONS: The studied targets hold little potential as indicators of disease severity. The serum values of our targets show robustness against atopic comorbidities, allergies and changes in disease severity. This robustness strengthens their potential use in biomarker-based stratification and could be instrumental in identifying subgroups and predicting the possible benefit of therapeutic and prevention approaches.

Who are the cancer survivors? A nationwide study in Denmark, 1943-2010.

BACKGROUND: No nationwide studies on social position and prevalence of comorbidity among cancer survivors exist. METHODS: We performed a nationwide prevalence study defining persons diagnosed with cancer 1943-2010 and alive on the census date 1 January 2011 as cancer survivors. Comorbidity was compared by social position with the non-cancer population. RESULTS: Cancer survivors composed 4% of the Danish population. Somatic comorbidity was more likely among survivors (OR 1.59, 95% CI 1.57-1.60) and associated with higher age, male sex, short education, and living alone among survivors. CONCLUSIONS: Among cancer survivors, comorbidity is common and highly associated with social position.

Screening for carcinoma in situ in the contralateral testicle in patients with testicular cancer: a population-based study.

BACKGROUND: Screening programmes for contralateral carcinoma in situ (CIS) testis in patients with unilateral germ-cell cancer (GCC) have never been evaluated. We investigated the effect of screening for contralateral CIS in a large nation-wide, population-based study. PATIENTS AND METHODS: A contralateral single-site biopsy was offered to 4130 patients in whom GCC had been diagnosed in 1984-2007 (screened cohort); 462 patients in whom GCC was diagnosed in 1984-1988 comprised the unscreened cohort. Cases with CIS were offered radiotherapy. Initially CIS-negative biopsies in patients with metachronous GCC were revised according to today's standards. Risk for metachronous GCC was estimated using cumulative incidence and the Cox proportional hazards model. RESULTS: In the screened cohort, contralateral CIS was found in 181 (4.4%) patients. The cumulative incidence of metachronous GCC after 20 years was 1.9% in the screened cohort and 3.1% in the unscreened cohort (P = 0.097), hazard ratio (HR) for the unscreened cohort: 1.59 (P = 0.144). Expert revision with contemporary methodology of CIS-negative biopsy samples from patients with metachronous cancer revealed CIS in 17 out of 45 (38%) cases. Decreased risks for metachronous GCC were related to older age at diagnosis (HR 0.52 per 10 years, P < 0.001) and chemotherapy (HR 0.35, P = 0.002). Limitations include the small number of patients in the unscreened cohort and the retrospective study design. CONCLUSIONS: Our evaluation of a national population-based screening programme for contralateral CIS in patients with testicular cancer showed no significant difference in the risk for metachronous GCC between a screened and an unscreened cohort. Single-site biopsy including modern immunohistochemistry does not identify all cases of CIS.

Aldara®-induced skin inflammation: studies of patients with psoriasis.

BACKGROUND: The application of Aldara(®) cream containing 5% imiquimod stimulates Toll-like receptor 7/8 on plasmacytoid dendritic cells, thereby producing a potent immunomodulatory effect. This has been reported to trigger psoriasis. OBJECTIVES: To establish a human model of Aldara-induced psoriasis-like skin inflammation in patients with psoriasis. METHODS: Nonlesional psoriatic skin of 13 patients was treated with Aldara for 2 or 7 days. The skin was evaluated clinically and histologically on days 2, 4 and 7. Cytokine expression in Aldara-treated, lesional and nonlesional psoriatic skin was compared using reverse-transcription quantitative polymerase chain reaction. RESULTS: Nine of the 10 patients receiving application of Aldara under occlusion for 2 days developed redness, induration and scaling. Histological analysis revealed focal parakeratosis, acanthosis and perivascular mononuclear infiltration. On days 4 and 7 both clinical and histological signs of inflammation subsided. Two of the three patients treated with Aldara for 7 days developed erosions leading to psoriasis on day 21. Cytokine markers of activation of the innate immune system [interferon-α, interferon regulatory factor-7 and interleukin (IL)-1ß] were equally expressed in lesional and Aldara-treated skin (n = 6). IL-6 and tumour necrosis factor-α were preferentially expressed in Aldara-treated skin. Adaptive immune system activation occurred only partially: IL-23p19 and IL-22 were similarly overexpressed in Aldara-treated and lesional psoriatic skin, but IL-17A and IL-12p40 were significantly underexpressed in Aldara-treated skin compared with lesional psoriatic skin. IL-10 was significantly overexpressed in Aldara-treated skin. CONCLUSIONS: We were able to induce psoriasis-like skin inflammation although typical psoriasis did not develop, possibly due to incomplete adaptive immune system recruitment and the powerful stimulation of IL-10 counter-regulation.

Changes in mRNA expression precede changes in microRNA expression in lesional psoriatic skin during treatment with adalimumab.

BACKGROUND: Tumour necrosis factor (TNF)-α inhibition is an effective treatment for moderate to severe plaque-type psoriasis. A change in the cytokine expression profile occurs in the skin after 4 days of treatment, preceding any clinical or histological improvements. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, but miRNA expression has never been studied in psoriatic skin during treatment. OBJECTIVE: To investigate changes in miRNA expression in psoriatic skin during adalimumab treatment and to compare results with changes in miRNA expression in a mouse model of Aldara-induced psoriasis-like skin inflammation. METHODS: Punch biopsies were obtained from nonlesional and lesional psoriatic skin during adalimumab treatment. In the mouse model of Aldara-induced skin inflammation, biopsies were obtained from TNF-α knockout (KO), IL-17A KO and wild-type mice. miRNA expression levels were analysed with microarray, reverse transcriptase quantitative polymerase chain reaction and in situ hybridization. RESULTS: In psoriatic skin, no changes in miRNA expression were seen 4 days after treatment initiation. After 14 days of treatment, the expression of several miRNAs was normalized towards the level seen in nonlesional skin before treatment. miR-23b expression increased after 14 days of treatment and remained high for 84 days, despite unaltered levels at baseline. In the mouse model of Aldara-induced skin inflammation, the level of miR-146a increased, whereas no regulation was seen for miR-203, miR-214-3p, miR-125a, miR-23b or let-7d-5p. CONCLUSIONS: This study demonstrates that the changes seen in the cytokine expression levels after 4 days of treatment with adalimumab are not facilitated by early changes in miRNA expression.

Interleukin-23 in early disease development in rheumatoid arthritis.

OBJECTIVES: To investigate the levels of interleukin (IL)-23 in patients with early rheumatoid arthritis (eRA) and the effect of anti-tumour necrosis factor (anti-TNF)-α treatment on IL-23 levels. METHOD: Treatment-naïve eRA patients from the OPERA cohort were included (n = 151). Patients were randomized to methotrexate (MTX) plus adalimumab (ADA; n = 75) or MTX plus placebo-ADA (PLA; n = 76). Plasma samples were obtained at baseline and at months 3, 6, and 12 together with values for C-reactive protein (CRP), the 28-joint Disease Activity Score based on CRP (DAS28CRP), scores on the Clinical Disease Activity Index (CDAI) and the Simplified Disease Activity Index (SDAI), visual analogue scale (VAS) for pain/fatigue/physician global and total Sharp/van der Heijde score (TSS). IL-23 was measured at each time point. RESULTS: IL-23 levels decreased significantly in the ADA group from 20.6 pg/mL (IQR 13.1-32.7 pg/mL) at baseline to 18 pg/mL (IQR 7.2-25.0 pg/mL) at 12 months (p < 0.01). No significant decrease in IL-23 level was observed in the PLA group. No associations between baseline IL-23 levels and measures of disease activity (DAS28CRP, CRP, CDAI, or SDAI) at 12 or 24 months were present in the treatment groups. Baseline IL-23 correlated inversely with changes in TSS and symptom duration before diagnosis. CONCLUSIONS: Our data show increased baseline levels and a significant decrease in IL-23 levels in eRA patients treated with anti-TNF-α. The inverse correlation with duration of symptoms before diagnosis supports the importance of IL-23 in the preclinical disease development of RA.

The effects of multidisciplinary rehabilitation: RePCa-a randomised study among primary prostate cancer patients.

BACKGROUND: The objective of this study is the effectiveness of multidisciplinary rehabilitation on treatment-related adverse effects after completed radiotherapy in patients with prostate cancer (PCa). METHODS: In a single-centre oncology unit in Odense, Denmark, 161 PCa patients treated with radiotherapy and androgen deprivation therapy were randomly assigned to either a programme of two nursing counselling sessions and two instructive sessions with a physical therapist (n=79) or to usual care (n=82). Primary outcome was Expanded Prostate Cancer Index Composite (EPIC-26) urinary irritative sum-score. Before radiotherapy, pre-intervention 4 weeks after radiotherapy, and after a 20-week intervention, measurements included self-reported disease-specific quality of life (QoL; EPIC-26, including urinary, bowel, sexual, and hormonal symptoms), general QoL (Short-form-12, SF-12), pelvic floor muscle strength (Modified Oxford Scale), and pelvic floor electromyography. Intension-to-treat analyses were made with adjusted linear regression. RESULTS: The intervention improved, as compared with controls, urinary irritative sum-score 5.8 point (Cohen's d=0.40; P=0.011), urinary sum-score (d=0.34; P=0.023), hormonal sum-score (d=0.19; P=0.018), and the SF-12 Physical Component Summary, d=0.35; P=0.002. Patients with more severe impairment gained most. Pelvic floor muscle strength measured by electromyography declined in both groups, P=0.0001. CONCLUSION: Multidisciplinary rehabilitation in irradiated PCa patients improved urinary and hormonal symptoms, and SF-12 physical QoL.

Socioeconomic position and survival after cervical cancer: influence of cancer stage, comorbidity and smoking among Danish women diagnosed between 2005 and 2010.

BACKGROUND: In an attempt to decrease social disparities in cancer survival, it is important to consider the mechanisms by which socioeconomic position influences cancer prognosis. We aimed to investigate whether any associations between socioeconomic factors and survival after cervical cancer could be explained by socioeconomic differences in cancer stage, comorbidity, lifestyle factors or treatment. METHODS: We identified 1961 cases of cervical cancer diagnosed between 2005 and 2010 in the Danish Gynaecological Cancer database, with information on prognostic factors, treatment and lifestyle. Age, vital status, comorbidity and socioeconomic data were obtained from nationwide administrative registers. Associations between socioeconomic indicators (education, income and cohabitation status) and mortality by all causes were analysed in Cox regression models with inclusion of possible mediators. Median follow-up time was 3.0 years (0.01-7.0). RESULTS: All cause mortality was higher in women with shorter rather than longer education (hazard ratio (HR), 1.46; 1.20-1.77), among those with lower rather than higher income (HR, 1.32; 1.07-1.63) and among women aged<60 years without a partner rather than those who cohabited (HR, 1.60; 1.29-1.98). Socioeconomic differences in survival were partly explained by cancer stage and less by comorbidity or smoking (stage- and comorbidity-adjusted HRs being 1.07; 0.96-1.19 for education and 1.15; 0.86-1.52 for income). CONCLUSION: Socioeconomic disparities in survival after cervical cancer were partly explained by socioeconomic differences in cancer stage. The results point to the importance of further investigations into reducing diagnosis delay among disadvantaged groups.

Psychiatric disorders in women with fertility problems: results from a large Danish register-based cohort study.

STUDY QUESTION: Do women who don't succeed in giving birth after an infertility evaluation have a higher risk of psychiatric disorders compared with women who do? SUMMARY ANSWER: The results indicated that being unsuccessful in giving birth after an infertility evaluation could be an important risk factor for psychiatric disorders. WHAT IS KNOWN ALREADY: Several studies have investigated the association between fertility treatment and psychological distress, but the results from these studies show substantial variation and lack of homogeneity that may be due to methodological limitations. STUDY DESIGN, SIZE AND DURATION: A retrospective cohort study was designed using data from a cohort of 98 320 Danish women evaluated for fertility problems during 1973-2008 and linked to several Danish population-based registries. All women were followed from the date of first infertility evaluation until date of hospitalization for the psychiatric disorder in question, date of emigration, date of death or 31 December 2008, whichever occurred first. Owing to the precise linkage between the infertility cohort and the Danish population-based registries, using the unique Danish personal identification number, virtually no women were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Information on reproductive status for all women in the infertility cohort was obtained by linkage to the Danish Medical Birth Registry. A total of 53 547 (54.5%) women gave birth after the initial infertility evaluation, whereas 44 773 (45.5%) women did not gave birth after the evaluation. To determine psychiatric disorders diagnosed in the women after enrolment in the infertility cohort, the cohort was linked to the Danish Psychiatric Central Registry. A total of 4633 women were hospitalized for a psychiatric disorder. The Cox proportional hazard regression model was applied to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between parity status after the initial infertility evaluation and risk of hospitalization for various groups of psychiatric disorders, including 'all mental disorders' and six main discharge subgroups labelled: 'alcohol and intoxicant abuse', 'schizophrenia and psychoses', 'affective disorders', 'anxiety, adjustment and obsessive compulsive disorders', 'eating disorder' and 'other mental disorders'. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence rate for all mental disorders was 393 cases per 100 000 person-years among women who did not succeed in giving birth after the infertility evaluation but only 353 cases per 100 000 person-years among women who succeeded in giving birth after the infertility evaluation. Women not giving birth after the infertility evaluation had an increased risk of hospitalization for all mental disorders (HR 1.17, 95% CI 1.11; 1.25), alcohol and intoxicant abuse (HR 2.02, 95% CI 1.69; 2.41), schizophrenia and psychoses (HR 1.46, 95% CI 1.17; 1.82) and other mental disorders (HR 1.42, 95% CI 1.27; 1.58) compared with women who gave birth after the infertility evaluation. In contrast, the risk of affective disorders (HR 0.90, 95% CI 0.81; 0.99) was decreased among women not giving birth after the infertility evaluation. Finally, the risk of anxiety, adjustment and obsessive compulsive disorders (HR 1.07, 95% CI 0.97; 1.17) as well as of eating disorders (HR 1.40, 95% CI 0.88; 2.22) was not significantly affected by parity status after the infertility evaluation. LIMITATIONS, REASON FOR CAUTION: As only psychiatric conditions warranting hospitalization could be included in the present study, the true incidence of all psychiatric disorders among women with fertility problems is likely to be somewhat underestimated. Furthermore, since detailed information on fertility treatment was not available for all cohort members the association between different modalities of assisted reproductive techniques and risk of psychiatric disorders was not assessed. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians and other healthcare personnel involved in diagnosis and treatment of women with fertility problems should be aware of the potential risk modification of psychiatric disorders associated with unsuccessful fertility treatment. Hence, our results may point to new aspects of follow-up of women with fertility problems who are unsuccessful in giving birth in order to prevent or identify and treat these possible psychological side effects. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Danish Cancer Society (award number: 96 222 54). All authors report no conflicts of interest.