BACKGROUND: Chronic pain patients with sensitization may exhibit decreased sensitivity to normally pruritogenic sensory stimuli and moreover occasionally perceive these as painful. This study explored the relationship between itch and pain, by evaluating histaminergic and non-histaminergic itch evoked in capsaicin-induced allodynic and hyperalgesic areas.

METHODS: In 28 healthy volunteers, capsaicin (100 μg/0.1 mL) was injected intradermally in the volar forearm to establish secondary dysesthesias. After the capsaicin-induced pain subsided, the areas of allodynia and hyperalgesia were mapped and itch was provoked inside these areas by histamine (10 mg/mL) and cowhage (25-40 spicules). The evoked itch and pain were recorded on a visual analogue scale (VAS 0-10 cm). Contralateral injection of 0.1 mL isotonic saline served as a control.

RESULTS: Histaminergic and non-histaminergic evoked itch were significantly decreased when provoked in allodynic skin (p < 0.05). The area-under-the-curve of the evoked itch was reduced -43% from 18.0 ± 2.6 cm10 min in normal skin to 10.3 ± 1.8 cm10 min in allodynic skin (p < 0.01) for cowhage and -56% from 20.0 ± 3.5 cm10 min in normal skin to 8.8 ± 2.3 cm10 min allodynic skin (p < 0.001) for histamine. The pain responses to the pruritogens were not significantly altered between the areas of allodynia and normal skin (p > 0.1). An additional experiment showed that pinprick hyperalgesia in the absence of allodynia was sufficient to evoke the observed reduced sensitivity to itch stimuli.

CONCLUSIONS: Cutaneous sensitization (secondary allodynia and hyperalgesia) reduced itch responses regardless of the type of itch model applied and without attenuation of the associated pruritogen-induced pain responses. This could explain the decreased sensitivity to itch provocations previously observed in patients with chronic pain.

SIGNIFICANCE: This study shows that the neuronal sensitization processes underlying the development secondary hyperalgesia involve significant gating of histaminergic as well as non-histaminergic pruriceptive transmission. Because these itch provocations normally target specific subpopulations of C-nociceptors they could be of relevance for exploratory purposes in pain patients.

OBJECTIVE: To explore and compare the outcomes of adaptation and physical activity programmes regarding activities of daily living (ADL) ability following interdisciplinary rehabilitation in women with fibromyalgia.

METHODS: Participants (n = 85) were quasi-randomized to 16-week adaptation (ADAPT) or physical activity (ACTIVE) programmes following 2-week interdisciplinary rehabilitation. Primary outcomes were ADL motor and ADL process ability, measured with the Assessment of Motor and Process Skills (AMPS) at 4-week follow-up. Data were analysed per protocol.

RESULTS: Participants (ADAPT, n = 21; ACTIVE, n = 27) did not differ from withdrawers (n = 37). Improvements in ADL ability in the ADAPT (ADL motor mean change = 0.43 logits (95% confidence interval (95% CI) = 0.31-0.56); ADL process mean change = 0.34 logits (95% CI = 0.17-0.52)) and ACTIVE (ADL motor mean change = 0.33 logits (95% CI = 0.22-0.43); ADL process mean change = 0.25 logits (95% CI = 0.12-0.38)) groups were statistically significant, with no differences between groups. Responder analyses revealed that 63% of all participants obtained clinically relevant improvements in ADL motor ability and 48% in ADL process ability.

CONCLUSION: Although limited by a large drop-out, this exploratory study showed that both adaptation and physical activity programmes following interdisciplinary rehabilitation improved ADL ability in the majority of participants. ADL ability outcomes were independent of group allocation (ADAPT vs ACTIVE), suggesting efficacy of both programmes.

Many patients with bipolar disorder (BD) experience debilitating cognitive deficits, with risk of impaired occupational and psychosocial functioning. However, knowledge of how these deficits impact the patients' ability to perform Activities of Daily Living (ADL), tasks related to self-care and domestic life is limited. We explored the relation between impaired cognitive function and the ability to perform ADL in patients with BD. A total of 42 outpatients (mean age 36 years (range 19.0-58.0 years), 69% women) with BD in remission and with subjective cognitive complaints (≥ 13 on the Cognitive Complaints in Bipolar Disorder Rating Assessment questionnaire (COBRA)) were included. Objective neurocognitive function was evaluated with a short comprehensive cognitive test battery and ADL ability was evaluated with the performance-based Assessment of Motor and Process Skills (AMPS) in the homes of the patients. Our findings indicate that low processing speed correlated with decreased ADL ability, and processing speed as measured by the cognitive test battery thus seems to be significantly related to patients' ability to live independently in the community. Overall, adding a performance based test to assess ADL ability in patients with BD home-surroundings seems to provide new insights regarding the effect of cognitive impairment in patients with BD.

OBJECTIVE: To identify a core set of domains (outcomes) to be measured in psoriatic arthritis (PsA) clinical trials that represent both patients' and physicians' priorities.

METHODS: We conducted (1) a systematic literature review (SLR) of domains assessed in PsA; (2) international focus groups to identify domains important to people with PsA; (3) two international surveys with patients and physicians to prioritise domains; (4) an international face-to-face meeting with patients and physicians using the nominal group technique method to agree on the most important domains; and (5) presentation and votes at the Outcome Measures in Rheumatology (OMERACT) conference in May 2016. All phases were performed in collaboration with patient research partners.

RESULTS: We identified 39 unique domains through the SLR (24 domains) and international focus groups (34 domains). 50 patients and 75 physicians rated domain importance. During the March 2016 consensus meeting, 12 patients and 12 physicians agreed on 10 candidate domains. Then, 49 patients and 71 physicians rated these domains' importance. Five were important to >70% of both groups: musculoskeletal disease activity, skin disease activity, structural damage, pain and physical function. Fatigue and participation were important to >70% of patients. Patient global and systemic inflammation were important to >70% of physicians. The updated PsA core domain set endorsed by 90% of OMERACT 2016 participants includes musculoskeletal disease activity, skin disease activity, pain, patient global, physical function, health-related quality of life, fatigue and systemic inflammation.

CONCLUSIONS: The updated PsA core domain set incorporates patients' and physicians' priorities and evolving PsA research. Next steps include identifying outcome measures that adequately assess these domains.

BACKGROUND: Cataract is the leading cause of blindness in low- and middle-income countries (LMICs), and the prevalence is inequitably distributed between and within countries. Interventions have been undertaken to improve cataract surgical services, however, the effectiveness of these interventions on promoting equity is not known.

OBJECTIVES: To assess the effects on equity of interventions to improve access to cataract services for populations with cataract blindness (and visual impairment) in LMICs.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 3), MEDLINE Ovid (1946 to 12 April 2017), Embase Ovid (1980 to 12 April 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 12 April 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 12 April 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 12 April 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 12 April 2017. We did not use any date or language restrictions in the electronic searches for trials.

SELECTION CRITERIA: We included studies that reported on strategies to improve access to cataract services in LMICs using the following study designs: randomised and quasi-randomised controlled trials (RCTs), controlled before-and-after studies, and interrupted time series studies. Included studies were conducted in LMICs, and were targeted at disadvantaged populations, or disaggregated outcome data by 'PROGRESS-Plus' factors (Place of residence; Race/ethnicity/ culture/ language; Occupation; Gender/sex; Religion; Education; Socio-economic status; Social capital/networks. The 'Plus' component includes disability, sexual orientation and age).

DATA COLLECTION AND ANALYSIS: Two authors (JR and JP) independently selected studies, extracted data and assessed them for risk of bias. Meta-analysis was not possible, so included studies were synthesised in table and text.

MAIN RESULTS: From a total of 2865 studies identified in the search, two met our eligibility criteria, both of which were cluster-RCTs conducted in rural China. The way in which the trials were conducted means that the risk of bias is unclear. In both studies, villages were randomised to be either an intervention or control group. Adults identified with vision-impairing cataract, following village-based vision and eye health assessment, either received an intervention to increase uptake of cataract surgery (if their village was an intervention group), or to receive 'standard care' (if their village was a control group).One study (n = 434), randomly allocated 26 villages or townships to the intervention, which involved watching an informational video and receiving counselling about cataract and cataract surgery, while the control group were advised that they had decreased vision due to cataract and it could be treated, without being shown the video or receiving counselling. There was low-certainty evidence that providing information and counselling had no effect on uptake of referral to the hospital (OR 1.03, 95% CI 0.63 to 1.67, 1 RCT, 434 participants) and little or no effect on the uptake of surgery (OR 1.11, 95% CI 0.67 to 1.84, 1 RCT, 434 participants). We assessed the level of evidence to be of low-certainty for both outcomes, due to indirectness of evidence and imprecision of results.The other study (n = 355, 24 towns randomised) included three intervention arms: free surgery; free surgery plus reimbursement of transport costs; and free surgery plus free transport to and from the hospital. These were compared to the control group, which was reminded to use the "low-cost" (˜USD 38) surgical service. There was low-certainty evidence that surgical fee waiver with/without transport provision or reimbursement increased uptake of surgery (RR 1.94, 95% CI 1.14 to 3.31, 1 RCT, 355 participants). We assessed the level of evidence to be of low-certainty due to indirectness of evidence and imprecision of results.Neither of the studies reported our primary outcome of change in prevalence of cataract blindness, or other outcomes such as cataract surgical coverage, surgical outcome, or adverse effects. Neither study disaggregated outcomes by social subgroups to enable further assessment of equity effects. We sought data from both studies and obtained data from one; the information video and counselling intervention did not have a differential effect across the PROGRESS-Plus categories with available data (place of residence, gender, education level, socioeconomic status and social capital).

AUTHORS' CONCLUSIONS: Current evidence on the effect on equity of interventions to improve access to cataract services in LMICs is limited. We identified only two studies, both conducted in rural China. Assessment of equity effects will be improved if future studies disaggregate outcomes by relevant social subgroups. To assist with assessing generalisability of findings to other settings, robust data on contextual factors are also needed.

This PhD thesis is based on three scientific papers. In 2011 the Parker Institute the department of rheumatology introduced standing weight-bearing MRI (G-Scan, ESAOTE, Genova, Italy) in the diagnostic of low back pain patients. Unfortunately, we experienced a substantial risk of fainting (orthostatic syncope) during standing pMRI. In paper 1 we present in an observational study that the risk of fainting (19%) during standing pMRI could almost be eliminated by the use of an external pneumatic compression device (2%). The lumbar lordosis in the standing position is a significant contributor to positional changes in the morphology in the lumbar spine. In paper 2, we present in an observational study that changes in lumbar lordosis angle (ΔLA) between the conventional supine and standing position were independent of pain and the degenerative disc score. Before a full introduction of standing pMRI in clinical practice, it is important to know if the interpretation of positional changes in common degenerative findings has a sufficient reproducibility. In paper 3, we present in a reliability study that the pMRI evaluation has a fair to substantial reliability, although positional changes in the lumbar spine's morphology from the supine to the standing seems a less reliable outcome. There are currently no international evidence-based recommendations for the use of standing pMRI, and we have limited knowledge about how to interpret these positional changes in the lumbar spine into a clinical context. Therefore, further research is warranted to test the precision (sensitivity and specificity) in prospective longitudinal studies or RCTs. However, from a clinical perspective it seems logical to scan patients with low back pain in the position worsening their symptoms - typically the upright position. Therefore, standing pMRI may provide a higher diagnostic specificity and additional benefit to low back pain patients in the future.