Retrospective case note review of chronic spontaneous urticaria outcomes and adverse effects in patients treated with omalizumab or ciclosporin in UK secondary care.

BACKGROUND: Omalizumab is approved in the UK as add-on treatment for chronic spontaneous urticaria (CSU) in patients with inadequate response to H1-antihistamines. Ciclosporin is an established but unlicensed 3rd line option for CSU. Two parallel retrospective observational studies were conducted to describe outcomes of treatment and adverse events with omalizumab or ciclosporin for CSU treatment. METHODS: Data from UK specialist centres prescribing omalizumab (five centres) or ciclosporin (three centres) in CSU patients were collected from hospital records by clinical staff and pooled for analysis. RESULTS: Forty-six patients prescribed omalizumab and 72 patients prescribed ciclosporin were included. Twenty-two (48%) omalizumab-treated patients had paired Urticaria Activity Scores (UAS7), showing a 25.4 point improvement during treatment (P < 0.0001). Paired Dermatology Life Quality Index (DLQI) was available in 28 (61%) omalizumab-treated and 17 (24%) ciclosporin-treated patients. At least a 75% improvement in DLQI score was observed in 79% of omalizumab-treated and 41% of ciclosporin-treated patients, and 65% of omalizumab-treated patients had complete resolution of their quality-of-life impairment (DLQI 0-1) versus 21% of ciclosporin-treated patients. Clinician comments reported symptom clearance in 15/36 (42%) omalizumab-treated and 10/60 (17%) ciclosporin-treated patients. Proportions of patients with adverse events were similar but those for omalizumab resembled CSU symptoms, making causality assignment difficult, whereas those for ciclosporin were consistent with its known adverse effect profile. CONCLUSIONS: Validated patient-reported measures of disease severity and quality of life should be used routinely in CSU management. Based on clinician comments and DLQI scores, symptoms and quality of life showed a greater improvement in the omalizumab-treated cohort than in the ciclosporin-treated cohort

The metabolic syndrome adds utility to the prediction of mortality over its components: The Vietnam Experience Study

Background\ud The metabolic syndrome increases mortality risk. However, as “non-affected” individuals may still have up to two risk factors, the utility of using three or more components to identify the syndrome, and its predictive advantage over individual components have yet to be determined.\ud \ud Methods\ud Participants, male Vietnam-era veterans (n = 4265) from the USA, were followed-up from 1985/1986 for 14.7 years (61,498 person-years), and all-cause and cardiovascular disease deaths collated. Cox's proportional-hazards regression was used to assess the effect of the metabolic syndrome and its components on mortality adjusting for a wide range of potential confounders.\ud \ud Results\ud At baseline, 752 participants (17.9%) were identified as having metabolic syndrome. There were 231 (5.5%) deaths from all-causes, with 60 from cardiovascular disease. After adjustment for a range of covariates, the metabolic syndrome increased the risk of all-cause, HR 2.03, 95%CI 1.52, 2.71, and cardiovascular disease mortality, HR 1.92, 95%CI 1.10, 3.36. Risk increased dose-dependently with increasing numbers of components. The increased risk from possessing only one or two components was not statistically significant. The adjusted risk for four or more components was greater than for only three components for both all-cause, HR 2.30, 95%CI 1.45, 3.66 vs. HR 1.70, 95%CI 1.11, 2.61, and cardiovascular disease mortality, HR 3.34, 95%CI 1.19, 9.37 vs. HR 2.81, 95%CI 1.07, 7.35. The syndrome was more informative than the individual components for all-cause mortality, but could not be assessed for cardiovascular disease mortality due to multicollinearity. Hyperglycaemia was the individual strongest parameter associated with mortality.\ud \u

Can we really say getting stronger makes your tendon feel better? No current evidence of a relationship between change in Achilles tendinopathy pain or disability and changes in Triceps Surae structure or function when completing rehabilitation: A systematic review

Objectives: Determine if improvements in pain and disability in patients with mid-portion Achilles tendinopathy relate to changes in muscle structure and function whilst completing exercise rehabilitation. Design: A systematic review exploring the relationship between changes in pain/disability and muscle structure/function over time, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods: Six online databases and the grey literature were searched from database inception to 16th December 2022 whereas clinical trial registries were searched from database inception to 11th February 2020. We included clinical studies where participants received exercise rehabilitation (± placebo interventions) for mid-portion Achilles tendinopathy if pain/disability and Triceps Surae structure/function were measured. We calculated Cohen\u27s d (95 % confidence intervals) for changes in muscle structure/function over time for individual studies. Data were not pooled due to heterogeneity. Study quality was assessed using a modified Newcastle–Ottawa Scale. Results: Seventeen studies were included for synthesis. No studies reported the relationship between muscle structure/function and pain/disability changes. Twelve studies reported muscle structure/function outcome measures at baseline and at least one follow-up time-point. Three studies reported improvements in force output after treatment; eight studies demonstrated no change in structure or function; one study did not provide a variation measure, precluding within group change over time calculation. All studies were low quality. Conclusions: No studies explored the relationship between changes in tendon pain and disability and changes in muscle structure and function. It is unclear whether current exercise-based rehabilitation protocols for mid-portion Achilles tendinopathy improve muscle structure or function. Systematic review registration: PROSPERO (registration number: CRD42020149970)

What influences practitioners’ readiness to deliver psychological interventions by telephone? A qualitative study of behaviour change using the Theoretical Domains Framework

Background Contemporary health policy is shifting towards remotely delivered care. A growing need to provide effective and accessible services, with maximal population reach has stimulated demand for flexible and efficient service models. The implementation of evidence-based practice has been slow, leaving many services ill equipped to respond to requests for non-face-to-face delivery. To address this translation gap, and provide empirically derived evidence to support large-scale practice change, our study aimed to explore practitioners’ perspectives of the factors that enhance the delivery of a NICE-recommended psychological intervention, i.e. guided self-help by telephone (GSH-T), in routine care. We used the Theoretical Domains Framework (TDF) to analyse our data, identify essential behaviour change processes and encourage the successful implementation of remote working in clinical practice. Method Thirty-four psychological wellbeing practitioners (PWPs) from the UK NHS Improving Access to Psychological Therapies (IAPT) services were interviewed. Data were first analysed inductively, with codes cross-matched deductively to the TDF. Results Analysis identified barriers to the delivery, engagement and implementation of GSH-T, within eight domains from the TDF: (i) Deficits in practitioner knowledge, (ii) Sub-optimal practitioner telephone skills, (iii) Practitioners’ lack of beliefs in telephone capabilities and self-confidence, (iv) Practitioners’ negative beliefs about consequences, (v) Negative emotions, (vi) Professional role expectations (vii) Negative social influences, and (viii) Challenges in the environmental context and resources. A degree of interdependence was observed between the TDF domains, such that improvements in one domain were often reported to confer secondary advantages in another. Conclusions Multiple TDF domains emerge as relevant to improve delivery of GSH-T; and these domains are theoretically and practically interlinked. A multicomponent approach is recommended to facilitate the shift from in-person to telephone-based service delivery models, and prompt behaviour change at practitioner, patient and service levels. At a minimum, the development of practitioners’ telephone skills, an increase in clients’ awareness of telephone-based treatment, dilution of negative preconceptions about telephone treatment, and robust service level guidance and standards for implementation are required. This is the first study that provides clear direction on how to improve telephone delivery and optimise implementation, aligning with current mental health policy and service improvement

Yield of comparative genomic hybridization microarray in pediatric neurology practice

OBJECTIVE: The present study investigated the diagnostic yield of array comparative genomic hybridization (aCGH) in a large cohort of children with diverse neurologic disorders as seen in child neurology practice to test whether pathogenic copy number variants (CNVs) were more likely to be detected in specific neurologic phenotypes. METHODS: A retrospective cross-sectional analysis was performed on 555 children in whom a genetic etiology was suspected and who underwent whole-genome aCGH testing between 2006 and 2012. Neurologic phenotyping was performed using hospital medical records. An assessment of pathogenicity was made for each CNV, based on recent developments in the literature. RESULTS: Forty-seven patients were found to carry a pathogenic CNV, giving an overall diagnostic yield of 8.59%. Certain phenotypes predicted for the presence of a pathogenic CNV, including developmental delay (odds ratio [OR] 3.69 [1.30–10.51]), cortical visual impairment (OR 2.73 [1.18–6.28]), dysmorphism (OR 2.75 [1.38–5.50]), and microcephaly (OR 2.16 [1.01–4.61]). The combination of developmental delay/intellectual disability with dysmorphism and abnormal head circumference was also predictive for a pathogenic CNV (OR 2.86 [1.02–8.00]). For every additional clinical feature, there was an increased likelihood of detecting a pathogenic CNV (OR 1.18 [1.01–1.38]). CONCLUSIONS: the use of aCGH led to a pathogenic finding in 8.59% of patients. The results support the use of aCGH as a first tier investigation in children with diverse neurologic disorders, although whole-genome sequencing may replace aCGH as the detection method in the future. In particular, the yield was increased in children with developmental delay, dysmorphism, cortical visual impairment, and microcephaly

Efficacy and safety of abrocitinib monotherapy in adolescents and adults: a post hoc analysis of the phase 3 JAK1 atopic dermatitis efficacy and safety (JADE) REGIMEN clinical trial

Background: Differences in atopic dermatitis (AD) disease course and manifestation with age may extend to treatment response. Objective: To evaluate response maintenance with continuous-/reduced-dose abrocitinib or withdrawal and response to treatment reintroduction after flare in adolescent and adult participants in JADE REGIMEN (NCT03627767). Methods: Adolescents (12–17 years) and adults with moderate-to-severe AD responding to abrocitinib 200-mg induction were randomly assigned to 40-week maintenance with abrocitinib (200 mg/100 mg) or placebo. Patients who experienced flare during maintenance received rescue treatment. Results: Of 246 adolescents and 981 adults, 145/246 (58.9%) and 655/981 (66.8%), respectively, responded to induction. Similar proportions of adolescents and adults experienced flare during maintenance with abrocitinib 200 mg (14.9%/16.9%), 100 mg (42.9%/38.9%), and placebo (75.5%/78.0%). From the abrocitinib 200-mg, 100-mg, and placebo arms, respectively, Eczema Area and Severity Index response was recaptured by 28.6%, 25.0%, and 52.9% of adolescents and 34.3%, 33.7%, and 58.0% of adults; Investigator’s Global Assessment response, by 42.9%, 50.0%, and 73.5% of adolescents and 34.3%, 50.6%, and 74.1% of adults. Abrocitinib had a similar safety profile regardless of age; nausea incidence was higher in adolescents. Limitations: Adolescents represented 20% of the trial population. Conclusion: Abrocitinib was effective in preventing flare in adolescents and adults.Clinicaltrials.gov listing: NCT03627767

Is no news good news? Inconclusive genetic test results in BRCA1 and BRCA2 from patients and professionals' perspectives

<p>Abstract</p> <p>Background</p> <p>Women from families with a high risk of breast or ovarian cancer in which genetic testing for mutations in the <it>BRCA1/2 </it>genes is inconclusive are a vulnerable and understudied group. Furthermore, there are no studies of the professional specialists who treat them - geneticists, genetic counsellors/nurses, oncologists, gynaecologists and breast surgeons.</p> <p>Methods</p> <p>We conducted a small qualitative study that investigated women who had developed breast cancer under the age of 45 and who had an inconclusive <it>BRCA1/2 </it>genetic diagnostic test (where no mutations or unclassified variants were identified). We arranged three focus groups for affected women and their close female relatives - 13 women took part. We also interviewed 12 health professionals who were involved in the care of these women.</p> <p>Results</p> <p>The majority of the women had a good grasp of the meaning of their own or a family member's inconclusive result, but a few indicated some misunderstanding. Most of the women in this study underwent the test for the benefit of others in the family and none mentioned that they were having the test purely for themselves. A difficult issue for sisters of affected women was whether or not to undertake prophylactic breast surgery. The professionals were sensitive to the difficulties in explaining an inconclusive result. Some felt frustrated that technology had not as yet provided them with a better tool for prediction of risk.</p> <p>Conclusions</p> <p>Some of the women were left with the dilemma of what decision to make regarding medical management of their cancer risk. For the most part, the professionals believed that the women should be supported in whatever management decisions they considered best, provided these decisions were based on a complete and accurate understanding of the genetic test that had taken place in the family.</p