The management of Chronic Hand Eczema: A retrospective patient record review.

BACKGROUND: Chronic Hand Eczema (CHE) is a heterogeneous fluctuating inflammatory disease that represents a significant burden. Effective treatment options for moderate to severe CHE are limited. OBJECTIVES: To assess how patients with moderate to severe CHE are treated in clinical practice. METHODS: A retrospective, physician-led patient record review assessed the demographic, clinical and treatment characteristics of patients aged ≥18 years with CHE across seven countries. Each participating physician was requested to review records for their three most recent patients with moderate to severe CHE treated with a topical or systemic therapy. RESULTS: A total of 264 physicians, of whom 88.6% were dermatologists and 70.1% were predominantly or partly hospital-based, reviewed the records of 792 patients. Signs were present on hands only in 56.4% of patients and the mean time on current treatment was 16.7 months. Overall, 62.9% of patients received systemic therapy and almost one-quarter (23.4%) were treated with a biologic; 28.6% of patients were only treated with topical corticosteroids and/or topical calcineurin inhibitors. CONCLUSION: In patients with moderate to severe CHE, most received systemic therapy with one-quarter on biologic therapy. However, given that many of these treatments have limited evidence of efficacy in CHE, there is a need for studies specifically in patients with CHE as well as new therapeutic options.

Cutaneous secondary localization of multiple myeloma at Heparin injection sites.

We report two cases of multiple myeloma skin localizations at Heparin injections sites in patients followed at the University Hospital of Martinique. These skin manifestations on traumatized areas are a marker of aggressiveness in the natural history of multiple myeloma.

Investigating the relationship between pain indicators and observers' judgements of pain.

BACKGROUND: Due to the inherent subjectivity of pain, it is difficult to make accurate judgements of pain in others. Research has found discrepancies between the ways in which perceived "objective" (e.g., medical evidence of injury) and "subjective" information (e.g., self-report) influence judgements of pain. This study aims to explore which potential cues (depictions of sensory input, brain activation, self-reported pain and facial expressions) participants are most influenced by when evaluating pain in others. METHODS: First, 60 participants (23 women, 36 ± 10 years old) judged who was in more pain between two different pain indicators representing two different patients. These trials revealed which congruent indicator (i.e., two high pain indicators) would most influence participant decisions. Second, participants prescribed quantities of analgesia for one patient's pain based on two different pain indicators. These trials revealed which incongruent indicators (i.e., one high and one low indicator) would most influence participant decisions. RESULTS: As predicted, facial expressions were perceived as subjective and were the least likely, among all pain indicators, to influence observer's judgements of pain. Participants relied upon indicators they perceived as objective. Self-report pain ratings had the greatest influence on participants judgements about how much analgesic cream to prescribe and was perceived as objective by half of the participants. CONCLUSIONS: We found that in situations where incongruent information was presented about an individual's pain, participants relied on pain indicators that they perceived to be objective. The current study provides important insights about biases that people hold when making judgements of pain in others. SIGNIFICANCE: Interpretation and assessment of pain remains one of the largest barriers to pain management and involves complex, idiosyncratic processing. This study provides insights into what information participants view as critical in making attributions of pain when presented with multiple, seemingly incongruent sources of information.

Is Pain "All in your Mind"? Examining the General Public's Views of Pain.

By definition, pain is a sensory and emotional experience that is felt in a particular part of the body. The precise relationship between somatic events at the site where pain is experienced, and central processing giving rise to the mental experience of pain remains the subject of debate, but there is little disagreement in scholarly circles that both aspects of pain are critical to its experience. Recent experimental work, however, suggests a public view that is at odds with this conceptualisation. By demonstrating that the public does not necessarily endorse central tenets of the "mental" view of pain (subjectivity, privacy, and incorrigibility), experimental philosophers have argued that the public holds a more "body-centric" view than most clinicians and scholars. Such a discrepancy would have important implications for how the public interacts with pain science and clinical care. In response, we tested the hypothesis that the public is capable of a more "mind-centric" view of pain. Using a series of vignettes, we demonstrate that in situations which highlight mental aspects of pain the public can, and does, recognize pain as a mental phenomenon. We also demonstrate that the public view is subject to context effects, by showing that the public's view is modified when situations emphasizing mental and somatic aspects of pain are presented together.

Pain priors, polyeidism, and predictive power: a preliminary investigation into individual differences in ordinary thought about pain.

According to standard philosophical and clinical understandings, pain is an essentially mental phenomenon (typically, a kind of conscious experience). In a challenge to this standard conception, a recent burst of empirical work in experimental philosophy, such as that by Justin Sytsma and Kevin Reuter, purports to show that people ordinarily conceive of pain as an essentially bodily phenomenon-specifically, a quality of bodily disturbance. In response to this bodily view, other recent experimental studies have provided evidence that the ordinary ('folk') concept of pain is more complex than previously assumed: rather than tracking only bodily or only mental aspects of pain, the ordinary concept of pain can actually track either of these aspects. The polyeidic (or 'many ideas') analysis of the folk concept of pain, as proposed by Emma Borg et al., captures this complexity. Whereas previous empirical support for the polyeidic view has focused on the context-sensitivity of the folk concept of pain, here we discuss individual differences in people's 'pain priors'-namely, their standing tendencies to think of pain in relatively mind-centric or body-centric ways. We describe a preliminary empirical study and present a small number of findings, which will be explored further in future work. The results we discuss are part of a larger programme of work which seeks to integrate philosophical pain research into clinical practice. For example, we hypothesise that variations in how patients with chronic pain are thinking about pain could help predict their responses to treatment.

Efficacy of Brodalumab and Guselkumab in Patients with Moderate-to-Severe Plaque Psoriasis Who are Inadequate Responders to Ustekinumab: A Matching Adjusted Indirect Comparison.

PURPOSE: Both brodalumab and guselkumab improve skin clearance in patients with moderate-to-severe plaque psoriasis after inadequate response to ustekinumab. In the absence of a direct head-to-head comparison, the relative efficacy of brodalumab and guselkumab in non-responders to ustekinumab were compared using a matching-adjusted indirect comparison (MAIC). PATIENTS AND METHODS: Individual patient data for brodalumab (n = 121) were pooled from the AMAGINE-2 and -3 trials and adjusted using a propensity score reweighting method, so that baseline and week 16 characteristics matched the aggregate published data of patients with an inadequate response to ustekinumab who switched to guselkumab (n = 135) in the NAVIGATE trial. RESULTS: After inadequate response to ustekinumab, brodalumab resulted in significantly higher psoriasis area and severity index (PASI) 90 rates versus guselkumab at post-treatment switch week 12 (62.7% vs 48.1%, relative difference 14.6% [95% confidence interval [CI] 5.3-23.9], p = 0.002 [number needed to treat [NNT] = 6.8]) and week 36 (63.7% vs 51.1%; relative difference 12.6% [95% CI 4.1-21.0]; p = 0.004 [NNT = 7.9]) and PASI 100 rate at week 36 (40.3% vs 20.0%; relative difference 20.3% [95% CI 11.8-28.7]; p < 0.001 [NNT = 4.9]). CONCLUSION: In this MAIC, brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab. Switching to brodalumab in such patients may be a more effective strategy than switching to guselkumab.

Modeling the optimal sequence of biologic therapies in plaque psoriasis in Spain.

AIM: The purpose of this manuscript was to illustrate the impact of the place in the treatment sequence on the cost and cost-effectiveness of different biologics for patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: We developed a treatment sequence model and focused on seven different biological treatment options and 840 combinations of treatment sequences. The model converted cost of treatment to a cost per responder by dividing treatment cost by expected number of patients achieving PASI100 after 52 weeks of treatment. We used Spanish ex-factory price levels, dosing recommendations and real-world data on drug survival to calculate the treatment costs. RESULTS: The most cost-effective treatment sequence was brodalumab-risankizumab-guselkumab-ixekizumab, with a cost per responder of €139,281 during the first five years of treatment. In comparison, if brodalumab was not recommended as first-line therapy, total costs would increase by 7.4% to €149,616. If brodalumab was not recommended as any of the first four lines of treatment, total costs would increase by 13.1% to €157,527 relative to the most cost-effective treatment sequence. CONCLUSIONS: A sequential therapy model may improve efficiency in the treatment of psoriasis. According to our results, brodalumab as the first-line therapy in Spain leads to the most cost-effective treatment sequence.

Assessing the Quality and Coherence of Network Meta-Analyses of Biologics in Plaque Psoriasis: What Does All This Evidence Synthesis Tell Us?

INTRODUCTION: A range of treatments are available for moderate-to-severe psoriasis; however, there remains a paucity of direct comparisons of these in head-to-head trials. Network meta-analyses (NMA) allow comparisons of these to support clinical decision making. This systematic literature review assesses the methodological quality of NMAs available for moderate-to-severe psoriasis and compares their methods and results. Their validity and applicability for current practice is also assessed. METHODS: A systematic review of published NMAs of at least two biologics for moderate-to-severe psoriasis was undertaken. Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Library were last searched on 19 February 2020. The quality of NMAs was assessed using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) criteria. NMA methodology, funding, and results were compared and differences in results explored. RESULTS: Twenty-five analyses evaluating up to 19 different treatments at 8-24 weeks, and two analyses at 1 year, were included. Psoriasis Area Severity Index (PASI) response was assessed in 23, facilitating comparisons between NMAs. All NMAs met at least half of the ISPOR criteria. The major limitations were explaining the rationale for methodology, exploring effect modifiers, and consistency between direct and indirect estimates. The analyses differed in model type (Bayesian or frequentist), analysis of PASI response (binomial or multinomial), and analysis of different treatment doses (separate or pooled). PASI results were broadly similar, except for the Cochrane Collaboration NMA which provided lower estimates of treatment efficacy versus placebo. This analysis differed methodologically from others, including pooling data for different doses. CONCLUSIONS: Based on PASI 90 at induction, the majority of recent NMAs came to similar conclusions: interleukin (IL) 17 inhibitors (brodalumab, ixekizumab, secukinumab), IL-23 inhibitors (guselkumab and risankizumab) and infliximab were most efficacious, supporting the validity of NMAs in this clinical area. Decisions should be made using high-quality, up-to-date NMAs with assumptions relevant to clinical practice.

Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response.

INTRODUCTION: New generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head studies. However, studies comparing these new biologics directly to one another are limited. OBJECTIVES: To compare the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis. METHODS: A systematic review was undertaken to identify randomised controlled trials evaluating biologic treatments, apremilast and dimethyl fumarate. MEDLINE, MEDLINE In-Process, Embase and the Cochrane Library were searched from the 1st January 2000 to 22nd November 2018. A Bayesian network meta-analysis (NMA) using a random-effects multinomial likelihood model with probit link and meta-regression to adjust for cross-trial variation in placebo responses compared the efficacy of interventions at inducing different levels of Psoriasis Area and Severity Index (PASI) response during the induction period. A range of sensitivity analyses was undertaken. RESULTS: Seventy-seven trials (34,816 patients) were included in the NMA. The base-case analysis showed that all active treatments were superior to placebo. IL-17 inhibitors, guselkumab and risankizumab were found to be more efficacious than tildrakizumab, ustekinumab, all TNF inhibitors and non-biologic systemic treatments at inducing all levels of PASI response. In addition, brodalumab, ixekizumab and risankizumab were significantly more efficacious than secukinumab; no significant difference was found in the comparison with guselkumab. The greatest benefit of brodalumab, ixekizumab, guselkumab, and risankizumab was seen for PASI 90 and PASI 100 response. Results were consistent across all analyses. CONCLUSIONS: In the NMA brodalumab, ixekizumab, risankizumab and guselkumab showed the highest levels of short-term efficacy. There were differences in efficacy between treatments within the same class. Longer-term analyses are needed to understand differences between these drugs beyond induction in what is a life-long condition.

Salpingectomy at the time of hysterectomy for benign gynaecological disease: A comparison of surgical approaches.

Given that a significant percentage of high-grade serous cancers develop in the fallopian tube, it has been suggested that salpingectomy may prevent some of these malignancies. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists guidelines recommend prophylactic salpingectomy to be discussed with or offered to patients undergoing hysterectomy for benign indications. This study compares rates of salpingectomy at the time of hysterectomy for benign indications across different surgical approaches among Australian and New Zealand gynaecologists. Data were collected via SurgicalPerformance, a web-based surgical outcomes review and feedback software used by independent gynaecologic surgeons. Of 11 477 hysterectomy records available, 6608 were eligible for analysis. Rates of salpingectomy at vaginal hysterectomy (13%) were significantly lower (P < 0.001) compared to open abdominal (65%), laparoscopic (70%), laparoscopic-assisted vaginal (78%), or robotic hysterectomies (73%) and also lower than in hysterectomies converted to an open abdominal approach (73%).

On Deflationary Accounts of Human Action Understanding.

A common deflationary tendency has emerged recently in both philosophical accounts and comparative animal studies concerned with how subjects understand the actions of others. The suggestion emerging from both arenas is that the default mechanism for understanding action involves only a sensitivity to the observable, behavioural (non-mental) features of a situation. This kind of 'smart behaviour reading' thus suggests that, typically, predicting or explaining the behaviour of conspecifics does not require seeing the other through the lens of mental state attribution. This paper aims to explore and assess this deflationary move. In §1 I clarify what might be involved in a smart behaviour reading account via looking at some concrete examples. Then in §2 I critically assess the deflationary move, arguing that, at least in the human case, it would in fact be a mistake to assume that our default method of action understanding proceeds without appeal to mental state attribution. Finally in §3 I consider briefly how the positive view proposed here relates to discussions about standard two-system models of cognition.

Economic evaluation in short bowel syndrome (SBS): an algorithm to estimate utility scores for a patient-reported SBS-specific quality of life scale (SBS-QoL™).

PURPOSE: Condition-specific preference-based measures can offer utility data where they would not otherwise be available or where generic measures may lack sensitivity, although they lack comparability across conditions. This study aimed to develop an algorithm for estimating utilities from the short bowel syndrome health-related quality of life scale (SBS-QoL™). METHODS: SBS-QoL™ items were selected based on factor and item performance analysis of a European SBS-QoL™ dataset and consultation with 3 SBS clinical experts. Six-dimension health states were developed using 8 SBS-QoL™ items (2 dimensions combined 2 SBS-QoL™ items). SBS health states were valued by a UK general population sample (N = 250) using the lead-time time trade-off method. Preference weights or 'utility decrements' for each severity level of each dimension were estimated by regression models and used to develop the scoring algorithm. RESULTS: Mean utilities for the SBS health states ranged from -0.46 (worst health state, very much affected on all dimensions) to 0.92 (best health state, not at all affected on all dimensions). The random effects model with maximum likelihood estimation regression had the best predictive ability and lowest root mean squared error and mean absolute error, and was used to develop the scoring algorithm. CONCLUSIONS: The preference-weighted scoring algorithm for the SBS-QoL™ developed is able to estimate a wide range of utility values from patient-level SBS-QoL™ data. This allows estimation of SBS HRQL impact for the purpose of economic evaluation of SBS treatment benefits.

More questions for mirror neurons.

The mirror neuron system is widely held to provide direct access to the motor goals of others. This paper critically investigates this idea, focusing on the so-called 'intentional worry'. I explore two answers to the intentional worry: first that the worry is premised on too limited an understanding of mirror neuron behaviour (Sections 2 and 3), second that the appeal made to mirror neurons can be refined in such a way as to avoid the worry (Section 4). I argue that the first response requires an account of the mechanism by which small-scale gestures are supposedly mapped to larger chains of actions but that none of the extant accounts of this mechanism are plausible. Section 4 then briefly examines refinements of the mirror neuron-mindreading hypothesis which avoid the intentional worry. I conclude that these refinements may well be plausible but that they undermine many of the claims standardly made for mirror neurons.