Evaluating telehealth lifestyle therapy versus telehealth psychotherapy for reducing depression in adults with COVID-19 related distress: the curbing anxiety and depression using lifestyle medicine (CALM) randomised non-inferiority trial protocol.

BACKGROUND: There is increasing recognition of the substantial burden of mental health disorders at an individual and population level, including consequent demand on mental health services. Lifestyle-based mental healthcare offers an additional approach to existing services with potential to help alleviate system burden. Despite the latest Royal Australian New Zealand College of Psychiatrists guidelines recommending that lifestyle is a 'first-line', 'non-negotiable' treatment for mood disorders, few such programs exist within clinical practice. Additionally, there are limited data to determine whether lifestyle approaches are equivalent to established treatments. Using an individually randomised group treatment design, we aim to address this gap by evaluating an integrated lifestyle program (CALM) compared to an established therapy (psychotherapy), both delivered via telehealth. It is hypothesised that the CALM program will not be inferior to psychotherapy with respect to depressive symptoms at 8 weeks. METHODS: The study is being conducted in partnership with Barwon Health's Mental Health, Drugs & Alcohol Service (Geelong, Victoria), from which 184 participants from its service and surrounding regions are being recruited. Eligible participants with elevated psychological distress are being randomised to CALM or psychotherapy. Each takes a trans-diagnostic approach, and comprises four weekly (weeks 1-4) and two fortnightly (weeks 6 and 8) 90-min, group-based sessions delivered via Zoom (digital video conferencing platform). CALM focuses on enhancing knowledge, behavioural skills and support for improving dietary and physical activity behaviours, delivered by an Accredited Exercise Physiologist and Accredited Practising Dietitian. Psychotherapy uses cognitive behavioural therapy (CBT) delivered by a Psychologist or Clinical Psychologist, and Provisional Psychologist. Data collection occurs at baseline and 8 weeks. The primary outcome is depressive symptoms (assessed via the Patient Health Questionnaire-9) at 8 weeks. Societal and healthcare costs will be estimated to determine the cost-effectiveness of the CALM program. A process evaluation will determine its reach, adoption, implementation and maintenance. DISCUSSION: If the CALM program is non-inferior to psychotherapy, this study will provide the first evidence to support lifestyle-based mental healthcare as an additional care model to support individuals experiencing psychological distress. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12621000387820 , Registered 8 April 2021.

Use of an audit with feedback implementation strategy to promote medication error reporting by nurses.

AIMS AND OBJECTIVES: To outline the development and effect of an audit with feedback implementation strategy that intended to increase the rate of voluntary medication error reporting by nurses. BACKGROUND: Medication errors are a serious global health issue. Audit with feedback is a widely used implementation strategy that has potential to modify nurses' reporting behaviour and improve medication error reporting rates. DESIGN: Quasi-experimental implementation study (fulfilling the TIDieR checklist) with two pairs of matched wards at a private hospital in Australia was conducted from March 2015-September 2016. One ward from each pair was randomised to either the intervention or control group. METHOD: Nurses within intervention wards received audit with feedback on a quarterly basis over a 12-month implementation period. Control wards underwent quarterly audits only (without feedback). Feedback consisted of a one-page infographic poster, with content based on medication error data obtained from audits and the hospitals' risk management system (RiskMan). The primary outcome-rate of medication errors reported per month-was determined in both groups at pre-implementation, implementation and postimplementation phases. Differences between groups were compared using generalised linear mixed models with Poisson distribution and log link. RESULTS: A nonsignificant intervention effect was found for rate of medication errors reported per month. Interestingly, when combining data from both groups, a significant increasing time trend was observed for medication errors reported per month across pre-implementation and implementation phases (80% increase). CONCLUSIONS: The audit with feedback strategy developed in the present study did not effectively influence the voluntary reporting of medication errors by nurses. RELEVANCE TO CLINICAL PRACTICE: Despite the lack of intervention effects, the use of a published checklist to optimise the reporting quality of this study will contribute to the field by furthering the understanding of how to enhance audit with feedback implementation strategies for nurses.

Maternity service organisational interventions that aim to reduce caesarean section: a systematic review and meta-analyses.

BACKGROUND: Caesarean sections (CSs) are associated with increased maternal and perinatal morbidity, yet rates continue to increase within most countries. Effective interventions are required to reduce the number of non-medically indicated CSs and improve outcomes for women and infants. This paper reports findings of a systematic review of literature related to maternity service organisational interventions that have a primary intention of improving CS rates. METHOD: A three-phase search strategy was implemented to identify studies utilising organisational interventions to improve CS rates in maternity services. The database search (including Cochrane CENTRAL, CINAHL, MEDLINE, Maternity and Infant Care, EMBASE and SCOPUS) was restricted to peer-reviewed journal articles published from 1 January 1980 to 31 December 2017. Reference lists of relevant reviews and included studies were also searched. Primary outcomes were overall, planned, and unplanned CS rates. Secondary outcomes included a suite of birth outcomes. A series of meta-analyses were performed in RevMan, separated by type of organisational intervention and outcome of interest. Summary risk ratios with 95% confidence intervals were presented as the effect measure. Effect sizes were pooled using a random-effects model. RESULTS: Fifteen articles were included in the systematic review, nine of which were included in at least one meta-analysis. Results indicated that, compared with women allocated to usual care, women allocated to midwife-led models of care implemented across pregnancy, labour and birth, and the postnatal period were, on average, less likely to experience CS (overall) (average RR 0.83, 95% CI 0.73 to 0.96), planned CS (average RR 0.75, 95% CI 0.61 to 0.93), and episiotomy (average RR 0.84, 95% CI 0.74 to 0.95). Narratively, audit and feedback, and a hospital policy of mandatory second opinion for CS, were identified as interventions that have potential to reduce CS rates. CONCLUSION: Maternity service leaders should consider the adoption of midwife-led models of care across the maternity episode within their organisations, particularly for women classified as low-risk. Additional studies are required that utilise either audit and feedback, or a hospital policy of mandatory second opinion for CS, to facilitate the quantification of intervention effects within future reviews. PROSPERO REGISTRATION: CRD42016039458 ; prospectively registered.

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial.

BACKGROUND: Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. METHODS: We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3-5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604. FINDINGS: Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1-26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9-30·1), p=0·001. INTERPRETATION: Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. FUNDING: NIHR Health Technology Assessment Programme.

Barriers and enablers to the delivery of psychological care in the management of patients with type 2 diabetes mellitus in China: a qualitative study using the theoretical domains framework.

BACKGROUND: China has the largest number of type 2 diabetes mellitus (T2DM) cases globally and individuals with T2DM have an increased risk of developing mental health disorders and functional problems. Despite guidelines recommending that psychological care be delivered in conjunction with standard T2DM care; psychological care is not routinely delivered in China. Community Health Centre (CHC) doctors play a key role in the management of patients with T2DM in China. Understanding the behavioural determinants of CHC doctors in the implementation of psychological care recommendations allows for the design of targeted and culturally appropriate interventions. As such, this study aimed to examine barriers and enablers to the delivery of psychological care to patients with T2DM from the perspective of CHC doctors in China. METHODS: Two focus groups were conducted with 23 CHC doctors from Shenzhen, China. The discussion guide applied the Theoretical Domains Framework (TDF) that examines current practice and identifies key barriers and enablers perceived to influence practice. Focus groups were conducted with an interpreter, and were digitally recorded and transcribed. Two researchers independently coded transcripts into pre-defined themes using deductive thematic analysis. RESULTS: Barriers and enablers perceived by doctors as being relevant to the delivery of psychological care for patients with T2DM were primarily categorised within eight TDF domains. Key barriers included: CHC doctors' knowledge and skills; time constraints; and absence of financial incentives. Other barriers included: societal perception that treating psychological aspects of health is less important than physical health; lack of opinion leaders; doctors' intentional disregard of psychological care; and doubts regarding the efficacy of psychological care. In contrast, perceived enablers included: training of CHC doctors in psychological skills; identification of afternoon/evening clinic times when recommendations could be implemented; introduction of financial incentives; and the creation of a professional role (e.g. diabetes educator), that could implement psychological care recommendations to patients with T2DM. CONCLUSIONS: The utilisation of the TDF allowed for the comprehensive understanding of barriers and enablers to the implementation of psychological care recommendations for patients with T2DM, and consequently, has given direction to future interventions strategies aimed at improving the implementation of such recommendations.

Measuring chlorine bleach in biology and medicine.

BACKGROUND: Chlorine bleach, or hypochlorous acid, is the most reactive two-electron oxidant produced in appreciable amounts in our bodies. Neutrophils are the main source of hypochlorous acid. These champions of the innate immune system use it to fight infection but also direct it against host tissue in inflammatory diseases. Neutrophils contain a rich supply of the enzyme myeloperoxidase. It uses hydrogen peroxide to convert chloride to hypochlorous acid. SCOPE OF REVIEW: We give a critical appraisal of the best methods to measure production of hypochlorous acid by purified peroxidases and isolated neutrophils. Robust ways of detecting it inside neutrophil phagosomes where bacteria are killed are also discussed. Special attention is focused on reaction-based fluorescent probes but their visual charm is tempered by stressing their current limitations. Finally, the strengths and weaknesses of biomarker assays that capture the footprints of chlorine in various pathologies are evaluated. MAJOR CONCLUSIONS: Detection of hypochlorous acid by purified peroxidases and isolated neutrophils is best achieved by measuring accumulation of taurine chloramine. Formation of hypochlorous acid inside neutrophil phagosomes can be tracked using mass spectrometric analysis of 3-chlorotyrosine and methionine sulfoxide in bacterial proteins, or detection of chlorinated fluorescein on ingestible particles. Reaction-based fluorescent probes can also be used to monitor hypochlorous acid during phagocytosis. Specific biomarkers of its formation during inflammation include 3-chlorotyrosine, chlorinated products of plasmalogens, and glutathione sulfonamide. GENERAL SIGNIFICANCE: These methods should bring new insights into how chlorine bleach is produced by peroxidases, reacts within phagosomes to kill bacteria, and contributes to inflammation. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.

Osteoid osteoma of the foot and ankle--A systematic review.

BACKGROUND: Osteoid osteomas are responsible for 10% of benign bone tumours. Treatment typically involves surgical excision or radio frequency ablation. The aim of this systematic review is to evaluate reported cases of foot and ankle osteoid osteomas. METHODS: We conducted a systematic review of the literature using the online databases Medline and EMBASE. We included studies reporting osteoid osteoma diagnosed either radiologically or histologically. RESULTS: 94 studies were included reporting 223 cases; 70.5% were male, mean age was 23 years, 69% reported night pain and 72% responded to NSAIDs. The commonest affected bone was the talus. CT scan was the most useful radiological investigation and MRI missed the diagnosis in 34% of cases. The majority of patients underwent surgical excision but an increasing trend of ablation therapy was demonstrated. CONCLUSIONS: A high index of suspicion based on salient history and appropriate imaging are essential for timely identification and treatment.

Ceruloplasmin is an endogenous inhibitor of myeloperoxidase.

Myeloperoxidase is a neutrophil enzyme that promotes oxidative stress in numerous inflammatory pathologies. It uses hydrogen peroxide to catalyze the production of strong oxidants including chlorine bleach and free radicals. A physiological defense against the inappropriate action of this enzyme has yet to be identified. We found that myeloperoxidase oxidized 75% of the ascorbate in plasma from ceruloplasmin knock-out mice, but there was no significant loss in plasma from wild type animals. When myeloperoxidase was added to human plasma it became bound to other proteins and was reversibly inhibited. Ceruloplasmin was the predominant protein associated with myeloperoxidase. When the purified proteins were mixed, they became strongly but reversibly associated. Ceruloplasmin was a potent inhibitor of purified myeloperoxidase, inhibiting production of hypochlorous acid by 50% at 25 nm. Ceruloplasmin rapidly reduced Compound I, the Fe(V) redox intermediate of myeloperoxidase, to Compound II, which has Fe(IV) in its heme prosthetic groups. It also prevented the fast reduction of Compound II by tyrosine. In the presence of chloride and hydrogen peroxide, ceruloplasmin converted myeloperoxidase to Compound II and slowed its conversion back to the ferric enzyme. Collectively, our results indicate that ceruloplasmin inhibits myeloperoxidase by reducing Compound I and then trapping the enzyme as inactive Compound II. We propose that ceruloplasmin should provide a protective shield against inadvertent oxidant production by myeloperoxidase during inflammation.

The potentiation of myeloperoxidase activity by the glycosaminoglycan-dependent binding of myeloperoxidase to proteins of the extracellular matrix.

BACKGROUND: Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood. METHODS: We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested. RESULTS: MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed. CONCLUSIONS: Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins. GENERAL SIGNIFICANCE: Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins.

Oxidation contributes to low glutathione in the airways of children with cystic fibrosis.

Glutathione is an important antioxidant in the lungs but its concentration is low in the airways of patients with cystic fibrosis. Whether this deficit occurs from an early age or how oxidative stress contributes to lowering glutathione is unknown. We measured glutathione, its oxidation products, myeloperoxidase, and biomarkers of hypochlorous acid in bronchoalveolar lavage from children with cystic fibrosis and disease controls using mass spectrometry and immunological techniques. The concentration of glutathione was lower in bronchoalveolar lavage from children with cystic fibrosis, whereas glutathione sulfonamide, a specific oxidation product of hypochlorous acid, was higher. Oxidised glutathione and glutathione sulfonamide correlated with myeloperoxidase and a biomarker of hypochlorous acid. The percentage of glutathione attached to proteins was higher in children with cystic fibrosis than controls. Pulmonary infections in cystic fibrosis resulted in lower levels of glutathione but higher levels of oxidised glutathione and glutathione sulfonamide in bronchoalveolar lavage. The concentration of glutathione is low in the airways of patients with cystic fibrosis from an early age. Increased oxidation of glutathione by hypochlorous acid and its attachment to proteins contribute to this deficiency. Therapies targeted against myeloperoxidase may boost antioxidant defence and slow the onset and progression of lung disease in cystic fibrosis.

Barriers to the implementation of preconception care guidelines as perceived by general practitioners: a qualitative study.

BACKGROUND: Despite strong evidence of the benefits of preconception interventions for improving pregnancy outcomes, the delivery and uptake of preconception care and periconceptional folate supplementation remain low. General practitioners play a central role in the delivery of preconception care. Understanding general practitioners' perceptions of the barriers and enablers to implementing preconception care allows for more appropriate targeting of quality improvement interventions. Consequently, the aim of this study was to examine the barriers and enablers to the delivery and uptake of preconception care guidelines from general practitioners' perspective using theoretical domains related to behaviour change. METHODS: We conducted a qualitative study using focus groups consisting of 22 general practitioners who were recruited from three regional general practice support organisations. Questions were based on the theoretical domain framework, which describes 12 domains related to behaviour change. General practitioners' responses were classified into predefined themes using a deductive process of thematic analysis. RESULTS: Beliefs about capabilities, motivations and goals, environmental context and resources, and memory, attention and decision making were the key domains identified in the barrier analysis. Some of the perceived barriers identified by general practitioners were time constraints, the lack of women presenting at the preconception stage, the numerous competing preventive priorities within the general practice setting, issues relating to the cost of and access to preconception care, and the lack of resources for assisting in the delivery of preconception care guidelines. Perceived enablers identified by general practitioners included the availability of preconception care checklists and patient brochures, handouts, and waiting room posters outlining the benefits and availability of preconception care consultations. CONCLUSIONS: Our study has identified some of the barriers and enablers to the delivery and uptake of preconception care guidelines, as perceived by general practitioners. Relating these barriers to a theoretical domain framework provides a clearer understanding of some of the psychological aspects that are involved in the behaviour of general practitioners towards the delivery and uptake of preconception care. Further research prioritising these barriers and the theoretical domains to which they relate to is necessary before a methodologically rigorous intervention can be designed, implemented, and evaluated.

A multi-professional survey of UK practice in the use of intra-articular corticosteroid injection for symptomatic first metatarsophalangeal joint osteoarthritis.

BACKGROUND: The first metatarsophalangeal joint is the most common site of osteoarthritis (OA) in the foot and ankle. Intra-articular corticosteroid injections are widely used for this condition, but little is known about their use in practice. This study explored current practice within the UK National Health Service (NHS) relating to the administration of intra-articular corticosteroids for people with painful first metatarsophalangeal joint (MTPJ) OA. METHODS: A cross-sectional survey using Qualtrics online survey platform (Qualtrics, Provo, UT, USA), distributed through professional bodies, special interest groups, and social media. RESULTS: One hundred forty-four healthcare professionals responded, including podiatrists (53/144; 39%), orthopaedic surgeons (28/144; 19%), podiatric surgeons (26/144; 17%) and physiotherapists (24/144; 16%). Half of respondents administered up to 25 corticosteroid injections per year (67/136; 49%) but some administered more than fifty (21/136; 15%). Injections were administered across the healthcare system but were most common in hospital settings (64/136; 44%) followed by community (38/136; 26%), with less delivered in primary care (11/136; 8%). Half of respondents routinely used image-guidance, either ultrasound or x-ray/fluoroscopy (65/136; 48%) although over one third used none (52/136; 38%). Imaging guidance was more common amongst medical professionals (21/31; 68%) compared to non-medical health professionals (45/105; 43%). Overall, methylprednisolone acetate was the most common corticosteroid used. Medical professionals mostly injected methylprednisolone acetate (n = 15/27; 56%) or triamcinolone acetonide (n = 11/27; 41%), whereas premixed methylprednisolone acetate with lidocaine hydrochloride was the most common preparation used by non-medical health professionals (41/85; 48%). When injecting non premixed steroid, lidocaine hydrochloride (15/35; 43%) was the most common choice of local anaesthetic for non-medical health professionals but medical professionals showed more variation between lidocaine hydrochloride (8/23; 35%) levobupivacaine hydrochloride (9/23; 39%) and bupivacaine hydrochloride (5/23; 22%). CONCLUSIONS: Multiple professional groups regularly administer intra-articular corticosteroids for symptomatic first MTPJ OA across a range of NHS healthcare settings. Overall, methylprednisolone acetate was the most commonly administered steroid and lidocaine hydrochloride the most common local anaesthetic. There was large variation in the use of imaging guidance, type and dose of steroid, local anaesthetic, and clinical pathways used in the intra-articular injection of corticosteroids for people with first MTPJ OA.

Overcoming challenges in conducting systematic reviews in implementation science: a methods commentary.

Consolidation of the literature using systematic reviews is a critical way to advance a discipline and support evidence-based decision-making in healthcare. However, unique challenges exist that impact the conduct of systematic reviews in implementation science. In this commentary, we reflect on our combined experience to describe five key challenges unique to systematic reviews of primary implementation research. These challenges include (1) descriptors used in implementation science publications, (2) distinction between evidence-based interventions and implementation strategies, (3) assessment of external validity, (4) synthesis of implementation studies with substantial clinical and methodological diversity, and (5) variability in defining implementation 'success'. We outline possible solutions and highlight resources that can be used by authors of primary implementation research, as well as systematic review and editorial teams, to overcome the identified challenges and optimise the utility of future systematic reviews in implementation science.

Clinical evaluation of the Immulite® 1000 chemiluminescent immunoassay for measurement of equine serum insulin.

Introduction: Accurate quantitative analysis of equine insulin in blood samples is critical for assessing hyperinsulinemia in horses. Although there are various laboratory methods for evaluating equine serum insulin, different immunoassays show significant discrepancies between the determined insulin concentrations and are often not comparable. The aim of this study was to evaluate the Immulite® 1000 chemiluminescent immunoassay (CLIA) to establish independent laboratory and assay-specific cut values to provide an accurate diagnosis of hyperinsulinemia in horses. Thus, the analytical and clinical performance of Immulite® 1000 CLIA in terms of precision (intra- and inter-assay coefficient of variance, CV) and recovery upon dilution were evaluated and compared with radioimmunoassay (RIA), which has been previously validated for use in horses. Material and methods: Archived serum samples (n = 106) from six Quarter horse mares enrolled in the glucose phase of a Frequently Sampled Insulin and Glucose Test (FSIGT) study were used to measure blood insulin. Results: The Immulite® 1000 CLIA had good precision with acceptable intra- and inter-assay CVs, adequate recovery on dilution, and a strong correlation with the RIA (r = 0.974, P < 0.0001), with constant bias resulting in consistently lower values. Discussion: On this basis, the Immulite® 1000 Insulin Assay is valid for measuring equine serum insulin for diagnostic and monitoring purposes when cut values are appropriately adjusted.

Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.

Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.

Physical symptom reporting is associated with a tendency to experience somatosensory distortion.

OBJECTIVE: Theory suggests that a tendency to experience distortions in somatosensory awareness is associated with physical symptom reporting (i.e., somatization) but empirical evidence for this is lacking. This article describes research designed to test this hypothesis. METHODS: Somatosensory distortion was operationalized as the frequency of illusory touch experiences (i.e., false alarm rate) on the Somatic Signal Detection Task. Two studies correlated false alarms on this task with physical symptom reporting on the 15-item Patient Health Questionnaire, the first using a nonclinical sample (n = 35), the second using a clinical sample of endoscopy patients who were identified as having either medically explained (n = 25) or medically unexplained symptoms (n = 30). RESULTS: Scores on the 15-item Patient Health Questionnaire were positively correlated with false alarm rate in both studies (r = 0.288-0.506), even after controlling for trait anxiety, depression, anxiety (standardized ß range = 0.793-0.932, all p < .0001) and (in Study 2) somatosensory amplification and hypochondriacal worry (standardized ß range = 0.345-0.375, both p < .05). There was no difference in false alarm rate between patients with medically explained and medically unexplained symptoms (medically explained median range = 6.8 [3.7] to 6.8 [4.0] versus medically unexplained median range = 4.3 [3.9] to 5.6 [3.1], both p > .1). CONCLUSIONS: There seems to be a robust link between physical symptom reporting and the tendency to experience somatosensory distortion, consistent with recent cognitive theories. It may be possible to reduce the impact of somatization by developing treatments that target this tendency.

Use of wavefront encoding in optical interconnects and fiber switches for cross talk mitigation.

A technique of cross talk mitigation developed for liquid crystal on silicon spatial light modulator based optical interconnects and fiber switches is demonstrated. By purposefully introducing an appropriate aberration into the system, it is possible to reduce the worst-case cross talk by over 10 dB compared to conventional Fourier-transform-based designs. Tests at a wavelength of 674 nm validate this approach, and show that there is no noticeable reduction in diffraction efficiency. A 27% spot increase in beam diameter is observed, which is predicted to reduce at longer datacom and telecom wavelengths.

Application of the fractional Fourier transform to the design of LCOS based optical interconnects and fiber switches.

It is shown that reflective liquid crystal on silicon (LCOS) spatial light modulator (SLM) based interconnects or fiber switches that use defocus to reduce crosstalk can be evaluated and optimized using a fractional Fourier transform if certain optical symmetry conditions are met. Theoretically the maximum allowable linear hologram phase error compared to a Fourier switch is increased by a factor of six before the target crosstalk for telecom applications of -40 dB is exceeded. A Gerchberg-Saxton algorithm incorporating a fractional Fourier transform modified for use with a reflective LCOS SLM is used to optimize multi-casting holograms in a prototype telecom switch. Experiments are in close agreement to predicted performance.

Minimally invasive forefoot surgery: a cadaveric study.

BACKGROUND: Minimally invasive surgery (MIS) aims to improve cosmesis and minimize soft tissue disruption by using small skin incisions. When using MIS in the forefoot, there is concern about iatrogenic neurovascular and tendon damage. The aim of this anatomical study was to assess the risk of iatrogenic injury while performing MIS techniques. METHODS: Ten normal cadaveric feet were used. All of the procedures were performed in a cadaveric lab using a mini-C-arm by two surgeons: a consultant who has attended a cadaveric MIS training course but does not perform MIS in his regular practice (eight feet) and a registrar (resident) who was supervised by the same consultant (two feet). In each foot, the surgeon performed a lateral release, a minimally invasive chevron and Akin (MICA) procedure for the correction of hallux valgus, and a minimally invasive distal metatarsal extra-articular osteotomy (DMO). Each foot was then dissected to identify any neurovascular or tendon injury and photographed. RESULTS: The dorsal medial cutaneous and the plantar interdigital nerves were intact in all specimens. There was no apparent damage to the arterial plexus supplying the first metatarsal head. No flexor or extensor tendon injuries were identified. On examination of the osteotomies, the cuts were found not to be in the desired plane. In both MICA and DMO, the dissection also revealed some intact soft tissue at the osteotomy site, which may preserve vascularity and add stability to the osteotomy. CONCLUSIONS: Although there has been concern regarding neurovascular and tendon injury, the findings were consistent with minimal risk, which is consistent with reports in the literature. This study also reflects the challenges associated with performing the osteotomy in the desired plane, which may be related to the learning curve. CLINICAL RELEVANCE: This cadaveric study has demonstrated a minimal risk of neurovascular and tendon injury associated with minimally invasive techniques in the forefoot. However, the study emphasizes the need for excellent three-dimensional anatomy and suggests additional cadaveric training prior to attempting these techniques in clinical practice.