Real-world registry-based study on apremilast use in psoriasis and psoriatic arthritis in Finland.

OBJECTIVES: This study assessed the position of apremilast in the treatment pathway of psoriasis (PsO) and psoriatic arthritis (PsA) in Finnish clinical practice, compared the characteristics of apremilast and biologic therapy users, evaluated persistence with apremilast and identified factors influencing treatment discontinuation. METHOD: This retrospective study used data from Finnish national health registries. The target group was identified based on L40* diagnosis and medication records between 2015 and 2018. Treatment persistence was analysed using Kaplan-Meier curves and Cox regression. RESULTS: Of eligible patients (PsO 31 202; PsA 12 386), 1% (n = 471) used apremilast and 10% (n = 4214) biologics, apremilast users being older (mean age 55.9 vs 52.4 years, p < 0.001) with a higher Charlson comorbidity score (0.71 vs 0.54, p < 0.001). Most patients switched to apremilast from conventional synthetic therapy (PsO 75%; PsA 76%); 47% of patients remained on apremilast during the observation period (PsO 58%; PsA 42%). Most patients discontinuing apremilast switched to biologics (PsO 51%; PsA 51%). Apremilast persistence increased with age (p = 0.042) and was higher in PsO than in PsA (median 14 vs 11 months; p = 0.005). Compared to prior conventional synthetic therapy, prior biologic therapy decreased persistence (hazard ratio for discontinuation 2.15, 95% confidence interval 1.42-3.25). CONCLUSION: In Finnish clinical practice, apremilast is mainly used between conventional synthetic therapy and biologics, with at least as high treatment persistence as reported in previous studies. Apremilast users were older with higher comorbidity burden than biologics users.

Interventions to enhance recovery in healthy workers; a scoping review.

BACKGROUND: Faster recovery from work may help to prevent work-related ill health. AIMS: To provide a preliminary assessment of the range and nature of interventions that aim to improve recovery from cognitive and physical work. METHODS: A scoping review to examine the range and nature of the evidence, to identify gaps in the evidence base and to provide input for systematic reviews. We searched for workplace intervention studies that aimed at enhancing recovery. We used an iterative method common in qualitative research to obtain an overview of study elements, including intervention content, design, theory, measurements, effects and cost-effectiveness. RESULTS: We found 28 studies evaluating seven types of interventions mostly using a randomized controlled study design. For person-directed interventions, we found relaxation techniques, training of recovery experiences, promotion of physical activity and stress management. For work-directed interventions, there were participatory changes, work-break schedules and task variation. Most interventions were based on the conservation of resources and affect-regulation theories, none were based on the effort-recovery theory. The need for recovery (NfR) and the recovery experiences questionnaires (REQ) were used most often. Study authors reported a beneficial effect of the intervention in 14 of 26 published studies. None of the studies that used the NfR scale found a beneficial effect, whereas studies that used the REQ showed beneficial effects. Three studies indicated that interventions were not cost-effective. CONCLUSIONS: Feasible and possibly effective interventions are available for improving recovery from cognitive and physical workload. Systematic reviews are needed to determine their effectiveness.

Clonal variation in interferon response determines the outcome of oncolytic virotherapy in mouse CT26 colon carcinoma model.

In our earlier studies, Semliki Forest virus vector VA7 completely eliminated type I interferon (IFN-I)-unresponsive human U87-luc glioma xenografts, whereas interferon-responsive mouse gliomas proved refractory. Here, we describe in two clones of CT26 murine colon carcinoma, opposed patterns of IFN-I responsiveness and sensitivity to VA7. Both CT26WT and CT26LacZ clones secreted biologically active interferon in vitro upon virus infection but only CT26WT cells were protected. Focal infection of CT26WT cultures was self-limiting but could be rescued using IFN-I pathway inhibitor Ruxolitinib or antibody against IFNß. Whole transcriptome sequencing (RNA-Seq) and protein expression analysis revealed that CT26WT cells constitutively expressed 56 different genes associated with pattern recognition and IFN-I signaling pathways, spanning two reported anti-RNA virus gene signatures and 22 genes with reported anti-alphaviral activity. Whereas CT26WT tumors were strictly virus-resistant in vivo, infection of CT26LacZ tumors resulted in complete tumor eradication in both immunocompetent and severe combined immune deficient mice. In double-flank transplantation experiments, CT26WT tumors grew despite successful eradication of CT26LacZ tumors from the contralateral flank. Tumor growth progressed uninhibited also when CT26LacZ inoculums contained only a small fraction of CT26WT cells, demonstrating dominance of IFN responsiveness when heterogeneous tumors are targeted with interferon-sensitive oncolytic viruses.

Interventions for preventing voice disorders in adults.

BACKGROUND: Poor voice quality due to a voice disorder can lead to a reduced quality of life. In occupations where voice use is substantial it can lead to periods of absence from work. OBJECTIVES: To evaluate the effectiveness of interventions to prevent voice disorders in adults. SEARCH STRATEGY: We searched MEDLINE (PubMed, 1950 to 2006), EMBASE (1974 to 2006), CENTRAL (The Cochrane Library, Issue 2 2006), CINAHL (1983 to 2006), PsychINFO (1967 to 2006), Science Citation Index (1986 to 2006) and the Occupational Health databases OSH-ROM (to 2006). The date of the last search was 05/04/06. SELECTION CRITERIA: Randomised controlled clinical trials (RCTs) of interventions evaluating the effectiveness of treatments to prevent voice disorders in adults. For work-directed interventions interrupted time series and prospective cohort studies were also eligible. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Meta-analysis was performed where appropriate. MAIN RESULTS: We identified two randomised controlled trials including a total of 53 participants in intervention groups and 43 controls. One study was conducted with teachers and the other with student teachers. Both trials were poor quality. Interventions were grouped into 1) direct voice training, 2) indirect voice training and 3) direct and indirect voice training combined.1) Direct voice training: One study did not find a significant decrease of the Voice Handicap Index for direct voice training compared to no intervention.2) Indirect voice training: One study did not find a significant decrease of the Voice Handicap Index for indirect voice training when compared to no intervention.3) Direct and indirect voice training combined: One study did not find a decrease of the Voice Handicap Index for direct and indirect voice training combined when compared to no intervention. The same study did however find an improvement in maximum phonation time (Mean Difference -3.18 sec; 95 % CI -4.43 to -1.93) for direct and indirect voice training combined when compared to no intervention. No work-directed studies were found. None of the studies found evaluated the effectiveness of prevention in terms of sick leave or number of diagnosed voice disorders. AUTHORS' CONCLUSIONS: We found no evidence that either direct or indirect voice training or the two combined are effective in improving self-reported vocal functioning when compared to no intervention. The current practice of giving training to at-risk populations for preventing the development of voice disorders is therefore not supported by definitive evidence of effectiveness. Larger and methodologically better trials are needed with outcome measures that better reflect the aims of interventions.

Interventions for treating functional dysphonia in adults.

BACKGROUND: Poor voice quality due to functional dysphonia can lead to a reduced quality of life. In occupations where voice use is substantial it can lead to a loss of employment. OBJECTIVES: To evaluate the effectiveness of interventions to treat functional dysphonia in adults. SEARCH STRATEGY: We searched MEDLINE (PubMed, 1950 to 2006), EMBASE (1974 to 2006), CENTRAL (The Cochrane Library, Issue 2 2006), CINAHL (1983 to 2006), PsychINFO (1967 to 2006), Science Citation Index (1986 to 2006) and the Occupational Health databases OSH-ROM (to 2006). The date of the last search was 5(th) April 2006. SELECTION CRITERIA: Randomised controlled trials (RCTs) of interventions evaluating the effectiveness of treatments targeted at adults with functional dysphonia. For work-directed interventions interrupted time series and prospective cohort studies were also eligible. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Meta-analysis was performed where appropriate. MAIN RESULTS: We identified six randomised controlled trials including a total of 163 participants in intervention groups and 141 controls. One trial was high quality. Interventions were grouped into 1) Direct voice therapy 2) Indirect voice therapy 3) Combination of direct and indirect voice therapy and 4) Other treatments: pharmacological treatment and vocal hygiene instructions given by phoniatrist. No studies were found evaluating direct voice therapy on its own. One study did not show indirect voice therapy on its own to be effective when compared to no intervention. There is evidence from three studies for the effectiveness of a combination of direct and indirect voice therapy on self-reported vocal functioning (SMD -1.07; 95% CI -1.94 to -0.19), on observer-rated vocal functioning (WMD -13.00; 95% CI -17.92 to -8.08) and on instrumental assessment of vocal functioning (WMD -1.20; 95% CI -2.37 to -0.03) when compared to no intervention. The results of one study also show that the remedial effect remains significant for at least 14 weeks on self-reported vocal functioning (SMD -0.51; 95% CI -0.87 to -0.14) and on observer-rated vocal functioning (Buffalo Voice Profile) (WMD -0.80; 95% CI -1.14 to -0.46). There is also limited evidence from one study that the number of symptoms may remain lower for a year. The combined therapy with biofeedback was not shown to be more effective than combined therapy alone in one study nor was pharmacological treatment found to be more effective than vocal hygiene instructions given by phoniatrist in one study. Publication bias may have influenced the results. AUTHORS' CONCLUSIONS: Evidence is available for the effectiveness of comprehensive voice therapy comprising both direct and indirect therapy elements. Effects are similar in patients and in teachers and student teachers screened for voice problems. Larger and methodologically better studies are needed with outcome measures that match treatment aims.

Preventing occupational stress in healthcare workers.

BACKGROUND: Healthcare workers can suffer from occupational stress which may lead to serious mental and physical health problems. OBJECTIVES: To evaluate the effectiveness of work and person-directed interventions in preventing stress at work in healthcare workers. SEARCH STRATEGY: We searched the Cochrane Depression Anxiety and Neurosis Group trials Specialised Register, MEDLINE, PsychInfo and Cochrane Occupational Health Field database. SELECTION CRITERIA: Randomised controlled clinical trials (RCT) of interventions aimed at preventing psychological stress in healthcare workers. For work-directed interventions interrupted time series and prospective cohort were also eligible. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Meta-analysis and qualitative synthesis were performed where appropriate. MAIN RESULTS: We identified 14 RCTs, three cluster-randomised trials and two crossover trials, including a total of 1,564 participants in intervention groups and 1,248 controls. Two trials were of high quality. Interventions were grouped into 1) person-directed: cognitive-behavioural, relaxation, music-making, therapeutic massage and multicomponent; and 2) work-directed: attitude change and communication, support from colleagues and participatory problem solving and decision-making, and changes in work organisation. There is limited evidence that person-directed interventions can reduce stress (standardised mean difference or SMD -0.85; 95% CI -1.21, -0.49); burnout: Emotional Exhaustion (weighted mean difference or WMD -5.82; 95% CI -11.02, -0.63) and lack of Personal Accomplishment (WMD -3.61; 95% CI -4.65, -2.58); and anxiety: state anxiety (WMD -9.42; 95% CI -16.92, -1.93) and trait anxiety (WMD -6.91; 95% CI -12.80, -1.01). One trial showed that stress remained low a month after intervention (WMD -6.10; 95% CI -8.44, -3.76). Another trial showed a reduction in Emotional Exhaustion (Mean Difference or MD -2.69; 95% CI -4.20, -1.17) and in lack of Personal Accomplishment (MD -2.41; 95% CI -3.83, -0.99) maintained up to two years when the intervention was boosted with refresher sessions. Two studies showed a reduction that was maintained up to a month in state anxiety (WMD -8.31; 95% CI -11.49, -5.13) and trait anxiety (WMD -4.09; 95% CI -7.60, -0.58). There is limited evidence that work-directed interventions can reduce stress symptoms (Mean Difference or MD -0.34; 95% CI -0.62, -0.06); Depersonalization (MD -1.14; 95% CI -2.18, -0.10), and general symptoms (MD -2.90; 95% CI -5.16, -0.64). One study showed that the difference in stress symptom level was nonsignificant at six months (MD -0.19; 95% CI -0.49, 0.11). AUTHORS' CONCLUSIONS: Limited evidence is available for the effectiveness of interventions to reduce stress levels in healthcare workers. Larger and better quality trials are needed.

Capsule thickness of cataractous lenses with and without exfoliation syndrome.

Lens capsule thickness was measured in 105 cataractous lenses with and without exfoliation syndrome. The lenses were removed by intracapsular cryoextraction. Forty lenses (38%) showed exfoliation, while 65 (62%) were exfoliation negative. Thickness values were measured by light microscopy from the central anterior capsule, central posterior capsule and from the equator. The mean thickness values were for the central anterior capsule 8.2 +/- 3.2 mu, for the central posterior capsule 3.2 +/- 1.4 and for the equator 3.9 +/- 1.3. There was no statistical difference between the exfoliation-positive and exfoliation-negative lenses. The capsule thickness varied greatly throughout the present material. The highest value, 22.4 mu, was measured from an exfoliation-negative central anterior lens capsule of a male patient aged 33 years. The lowest value, 0.6 mu, was measured from an exfoliation-positive central posterior capsule of a male patient aged 64 years. The central posterior capsule is the thinnest area of the lens capsule. The findings call for great caution in polishing the posterior capsule during extracapsular cataract surgery. The higher complication rate in eyes with exfoliation syndrome cannot be explained by thinner lens capsules but rather on the more friable zonules.