Effectiveness of sequential lines of biologic and targeted small molecule drugs in psoriasis: A systematic review and meta-analysis.

To assess current evidence of effectiveness of sequential lines of biologic and targeted small molecule drugs for psoriasis beyond first line. A systematic search of the literature (Medline, Embase and bibliographic) was undertaken in October and December 2022 to find all studies assessing effectiveness of biologics and targeted small molecules when used beyond first-line in adults with psoriasis (PROSPERO CRD42022365298). Data extraction and a bias assessment (Risk Of Bias In Non-randomized Studies-of Interventions/Cochrane RoB2) were undertaken for all included studies. A random effects proportional meta-analysis was undertaken for PASI75/90/100 at 12-16 weeks for each line of treatment (1st to 4th). Of 2666 abstracts identified, a full text review was undertaken of 177 studies; 20 manuscripts met eligibility criteria. Twenty studies were included in the analysis: 19 observational studies and one sub analysis of a RCT; n = 6495 (average age 49.7 years, female 35.1%). Eleven studies assessed second line biologic, nine assessed third + line. A meta-analysis of PASI75 at 12-16 weeks found pooled effect percentage achieving PASI75 of 61%, 56%, 79% and 61% in 1st, 2nd, 3rd and 4th line biologics respectively. Meta-analyses of PASI90/100 also found no evidence of diminished effectiveness with sequential lines (PASI90 46.1%, 39.9%, 55.8% and 33.7% and PASI100 36.7%, 30.3%, 46.7% and 30.4% in 1st to 4th line respectively). Available evidence for effectiveness of biologics beyond first line in psoriasis is predominantly observational, at high risk of bias and of low quality. There is very limited data for effectiveness beyond second line. Evidence indicates that biologics can be effective to fourth-line.

Effectiveness of sequential lines of biologic and targeted small-molecule drugs in psoriatic arthritis: a systematic review.

OBJECTIVE: To assess current evidence for effectiveness of sequential lines of biologic and targeted small-molecule disease-modifying anti-rheumatic drugs (b/tsDMARDs) when used beyond first-line for psoriatic arthritis (PsA). METHODS: A systematic search of the literature (Medline, Embase, bibliographic searches) was undertaken (October and December 2022) to find studies meeting the criteria of assessing effectiveness of b/tsDMARDs beyond first-line in adults with PsA (PROSPERO CRD42022365298). Risk of bias assessment was undertaken (ROBINS-I/Cochrane RoB2). RESULTS: Of 2666 abstracts identified and following a full text review of 177 psoriatic disease studies, 12 manuscripts and two abstracts were eligible. Of the 12 manuscripts, 11 were observational and one was a sub-analysis of a RCT (n = 16 081: average age 49.5 years, female 53.3%). Two abstracts (n = 7186) were included. All studies comparing first- and second-line (three studies) found a reduced response in second-line. On average, DAPSA remission (most reported outcome, eight studies) was achieved in 26%, 19% and 10% first-, second- and third-line TNFi, and 22%, 13% and 11% first-, second- and third-line other bDMARDs, respectively. Responses varied to third-line bDMARDs; four studies found comparable second- and third-line responses, five studies found diminishing responses in sequential lines. CONCLUSION: Predominantly observational studies, inherently at high risk of bias, indicate bDMARDs can be effective to third-line in PsA, but that response is reduced after first line. There is very limited data for more advanced lines of b/tsDMARD. Prospective studies are required to better understand clinical response to advanced lines of treatment in PsA.

Where and how have written action plans for atopic eczema/dermatitis been developed and evaluated? Systematic review.

Background: Atopic eczema/dermatitis is a common inflammatory condition which affects 15%-30% of children and 2%-10% of adults. It can have a significant impact and its management can be challenging. It is important for patients, parents, and caregivers to know how to look after their skin. Objectives: To identify and review written eczema action plans (WAPs) that are available internationally for use by patients, parents, and caregivers. Methods: We followed Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines. We searched relevant databases (MEDLINE, Embase, COCHRANE) from inception until March 2022. We sought grey literature via Google searches and professional networks. Database search results were independently reviewed by two different reviewers. With identified WAPs, we assessed length, appearance, content, how it was developed and whether it had been evaluated. Results: From 312 abstracts, supplemented by other searches, we identified 20 unique eczema WAPs. From nine countries, all were written in English with 18 were designed for children. For the majority, it was unclear whether any development work preceded their creation or the intended clinical setting for use. Nineteen had a stepwise approach, 17 advised when to seek help, 6 were visually appealing and 6 had a rationale behind treatment documented in the WAP. Only three had been evaluated in clinical trials. Conclusion: Further evaluation is needed to assess the effectiveness of the WAPs that currently exist, prior to creating further WAPs. Patient and caregiver involvement is needed in any future work.

Frequency of guideline-defined cow's milk allergy symptoms in infants: Secondary analysis of EAT trial data.

BACKGROUND: Non-IgE-mediated Cow's Milk Allergy (CMA) has a prevalence of less than 1% in children. Guidelines developed to help non-specialists diagnose CMA may lead to misattribution of normal symptoms and contribute to overdiagnosis of CMA. We sought to establish the frequency of symptoms during infancy associated with non-IgE-mediated CMA, using the international Milk Allergy in Primary Care (iMAP) guideline as representative of CMA guidelines more generally. METHOD: Secondary analysis of the Enquiring About Tolerance (EAT) randomized controlled trial (ISRCTN 14254740; 1303 exclusively breastfed 3-month-old healthy infants). Key outcomes were ≥2 iMAP symptoms associated with 'mild-moderate' and 'severe' non-IgE-mediated CMA. RESULTS: Whilst breastfeeding and parental atopy rates were higher than the general population, participants were otherwise similar to the population of England and Wales. Two or more non-IgE CMA symptoms were reported by 25% families for mild-moderate and 1.4% for severe symptoms each month between ages 3 and 12 months, peaking at 38% with ≥2 mild-moderate and 4.3% ≥2 severe symptoms at three months, when participants were not directly consuming cow's milk. 74% of participants reported ≥2 mild-moderate symptoms and 9% ≥2 severe symptoms in at least one month during this period. At six months there was no evidence of difference in the proportion of children with ≥2 symptoms between those consuming (29.5% mild-moderate, 1.8% severe) and not consuming cow's milk (35.3% mild-moderate, 2.2% severe). Mean monthly reporting of ≥2 symptoms was also no different between those with (15.8% mild-moderate, 1.1% severe) or without eczema at baseline (16.7% mild-moderate, 1.3% severe). CONCLUSIONS: Guideline-defined symptoms of non-IgE-mediated CMA are very common in infants. Guidelines may promote milk allergy overdiagnosis by labelling normal infant symptoms as possible milk allergy.

Are we selecting appropriate admissions for intensive care following major abdominal surgery: A retrospective cohort study on outcomes of 1059 patients.

BACKGROUND: Like any other medical treatment, The intensive care unit (ICU) is a limited resource that needs to be utilized appropriately. This study aimed to identify the outcomes of patients admitted to the ICU based on patient demographic and severity score parameters. METHODS: An observational retrospective cohort study of 1059 patients undergoing laparotomy who were admitted to the ICU was performed. Cases were sub-classified by the mode of admission and risk prediction scores and analyzed outcomes of mortality, ICU length of stay (LOS), and hospital LOS. RESULTS: The mean age of patients who did not survive was older than those who survived, and higher Acute Physiology and Chronic Health Evaluation (APACHE) II and Intensive Care National Audit and Research Centre Physiology Score (ICNARC) observed in patients who died. Emergency admission was also an indicator of increased mortality. Survivors APACHE II scores were the same if they were elective or emergency admissions, although Survivors ICNARC scores were higher in emergency than in elective admissions. Patients who did not survive had a longer ICU LOS stay than those who survived, whereas elective survivors had shorter ICU LOS than the emergency survivors. Regardless of this hospital LOS was the same for both elective and emergency survivors. CONCLUSION: The most unwell patients had the highest risk prediction scores, were more often admitted in the emergency setting, required longer stays in ICU, and had less favorable outcomes. However, ICU did appear to expedite the hospital discharges of emergency patients to match their elective counterparts. Decisions around when and to which patients ICU is an appropriate intervention remains a difficult decision and one that cannot be made without full consideration of all aspects of patient factors.

Dermatology consultations: how long do they take?

The rising demand for dermatology services calls for more -efficient clinics. However, there is a lack of evidence to guide the allocation of time for dermatological consultations. Our study analysed 607 dermatology consultations led by 23 clinicians. Consultation lengths were found to be dependent on the grade of clinician seen, nature of attendance (new or follow-up) and nature of final diagnosis. The median times taken for all consultations involving general dermatological conditions or suspected skin tumours were 16.5 minutes (IQR 12.8-24.1) and 15.5 minutes (IQR 11.7-20.1), respectively (p=0.001). Consultations with new patients took longer than follow-up cases (p<0.001). Based on our results, new patients presenting with general dermatological conditions should be allocated 25 minutes per consultant-led consultation, while follow-up cases can be allocated 15 minutes per consultation. We recommend similar analyses of consultation lengths in other specialties to inform the development of efficient, specialty-specific clinic models.