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COVID-19, ataxia, myoclonus, SARS CoV-2 References 1 Godani M, Beronio A, Lanza G. Post-COVID-19 myoclonus-ataxia syndrome responsive to intravenous immunoglobulins. Keywords: COVID-19; SARS CoV-2; ataxia; myoclonus EN COVID-19 SARS CoV-2 ataxia myoclonus 724 725 2 04/18/23 20230401 NES 230401 We have read with interest the case report on post-COVID-19 myoclonus-ataxia syndrome responsive to intravenous immunoglobulins (IVIG).[1] In recent months, post COVID-19 motor complications have been described in several papers. [Extracted from the article]

Introduction: Female sex workers (FSWs) are at high-risk for HIV acquisition in South Africa, where the advent of new HIV prevention and treatment interventions represent the potential to significantly impact the epidemic. This paper focuses on aspects of PrEP acceptability as a new intervention within the context of a larger service delivery programme including the simultaneous rollout of early ART. This paper explores PrEP acceptability among the FGD participants as future potential users. Methods: FGDs were conducted in two clinic-based sites in Johannesburg and Pretoria. They aimed to explore community-level, multi-dimensional acceptability of PrEP within the context of imminent implementation alongside early ART in the TAPS Demonstration Project. Sex worker peer educators recruited participants from varying sex work locales. Facilitation was in English with adaptation by facilitators into local languages as needed. Transcripts were translated and transcribed into English. Thematic analysis was used to analyse the data. Results: Four FGDs were conducted in each site for a total of eight FDGs and 69 participants. Demographics were largely similar across the sites. Overall, there was strong acceptability of PrEP among participants and positive anticipation for the imminent delivery of PrEP in the local sex worker clinics. Themes arising from the discussions exploring aspects of PrEP acceptability included: awareness and understanding of PrEP; PrEP motivations including choice, control, and vulnerability, managing PrEP risks and worries; and, de-stigmatizing and empowering PrEP delivery. Participant discussions and recommendations highlighted the importance of developing clear education and messaging to accurately convey the concept of PrEP, and intervention integration into supportive and tailored services. Conclusions: Through the course of these FGDs, PrEP became a positive and highly anticipated prevention option among the FSWs participants who endorsed implementation in their communities. Effective integration of PrEP into existing services will include comprehensive health programming where ART is also available, appropriate messaging, and support. [ABSTRACT FROM AUTHOR]

Introduction: In 2004, the US government began to utilize the Food and Drug Administration's (USFDA) tentative approval process (tFDA) as a basis to determine which HIV drugs are appropriate to be purchased and used in resource-constrained settings. This process permits products that are not approved for marketing in the US, including medicines with active patents or marketing restrictions in the US, to be purchased and distributed in resource-constrained settings. Although the tFDA was originally intended to support the United States' President's Emergency Plan for AIDS Relief (PEPFAR), the USFDA list has become a cornerstone of international HIV programmes that support procurement of ARVs, such as the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Our objective in this article is to help the global HIV policy makers and implementers of HIV programmes better understand the benefits and limitations of the tFDA by providing an in-depth review of the relevant legal and regulatory processes. Discussion: USFDA's dedicated tFDA process for ARVs used by the PEPFAR programme has a wide impact globally; however, the implementation and the regulatory processes governing the programme have not been thoroughly described in the medical literature. This paper seeks to help stakeholders better understand the legal and regulatory aspects associated with review of ARVs under the tFDA by describing the following: (1) the tFDA and its importance to global ARV procurement; (2) the regulatory pathways for applications under tFDA for the PEPFAR programme, including modifications to applications, review timelines and costs; (3) the role of US patents, US marketing exclusivity rights, and the Medicines Patents Pool in tFDA; and (4) an overview of how applications for PEPFAR programme are processed through the USFDA. We also provide a case study of a new ARV, tenofovir alafenamide fumarate (TAF), not yet reviewed by USFDA for PEPFAR use. Conclusions: In this paper, we describe the importance and implementation of USFDA's tentative approval process to review ARVs for resource-constrained settings. We also highlight the impact of patents and exclusivities on review of HIV drugs under tFDA and illustrate the concepts using a new HIV drug as an example. [ABSTRACT FROM AUTHOR]

Objectives To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus-based guidance paper for the methodology and design of cognition trials in bipolar disorder. Methods The task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face-to-face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved. Results Key methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non-study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach. Conclusions This ISBD task force guidance paper provides the first consensus-based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Interstitial lung diseases ( ILD) are a diverse group of pulmonary diseases for which accurate diagnosis is critical for optimal treatment outcomes. Diagnosis of ILD can be challenging and a multidisciplinary approach is recommended in international guidelines. The purpose of this position paper is to review the evidence for the use of the multidisciplinary meeting ( MDM) in ILD and suggest an approach to its governance and constitution, in an attempt to provide a standard methodology that could be applied across Australia and New Zealand. This position paper is endorsed by the Thoracic Society of Australia and New Zealand ( TSANZ) and the Lung Foundation Australia ( LFA). [ABSTRACT FROM AUTHOR]

Aim: This paper describes the implementation of a Collaborative Model of Fieldwork Education in a regional hospital occupational therapy department. Methods: The literature on models of fieldwork education for occupational therapy students is reviewed, and an approach to the implementation of the collaborative model with three students to one clinical educator is described after piloting of this model's recommendations, arising from the pilot placement, are proposed. Conclusions: The implementation of a Collaborative Model of Fieldwork Education requires careful planning, close links with the university fieldwork team and a willingness on the behalf of occupational therapist clinical educators to explore alternative approaches to the provision of fieldwork education. [ABSTRACT FROM AUTHOR]

The continuing global increase in the prevalence of overweight and obesity, particularly amongst children, attracts widespread public and political attention. Obesity is a complex condition, with multi‐faceted determinants, and prevention strategies require consideration of dietary and lifestyle patterns alongside a range of environmental factors. Reduction in intake of sugar‐sweetened beverages and foods is advised around the world as part of healthier dietary patterns to help reduce energy intakes, obesity risk and obesity‐related disorders. Current intakes indicate that this is challenging and will likely require a concerted approach with a broad range of interventions including fiscal measures. In recent years, after some notable success with salt and trans fats, there has been considerable focus on food reformulation to support the reduction in population intakes of free sugars from manufactured foods, often without need for consumer behaviour change. In some products, particularly sugar‐sweetened beverages, reformulation is relatively easy and has been widely achieved, as the sweetness of sugars can be replaced with low‐calorie sweeteners. However, other products, in which sugar delivers a variety of functional properties, are more challenging to reformulate to maintain consumer acceptance and achieve a reduction in energy, alongside sugar, content. This paper will look at current definitions and recommendations for free (or added) sugars, as well as key dietary sources and trends in intakes, and explore various strategies to promote population reductions in intake of sugars for public health, including the opportunities and challenges presented by reformulation using low‐calorie sweeteners. Ultimately strategies to promote sugar reduction, including reformulation, should adopt a holistic approach that considers wider dietary recommendations. [ABSTRACT FROM AUTHOR]

We report the case of an adolescent with hypohidrotic ectodermal dysplasia, who had obsessive‐compulsive disorder and was later diagnosed with body dysmorphic disorder (BDD). BDD is a highly distressing, adolescent‐onset disorder that may lead to social isolation, the development of comorbid mental health disorders and suicidality. Patients typically lack insight into their BDD and frequently present to dermatologists for medical treatment. In this paper, we address the challenges faced when working with patients with BDD. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to the Rössle et al papers. To view these articles, visit https://doi.org/10.1111/apt.15811 and https://doi.org/10.1111/apt.15930 [ABSTRACT FROM AUTHOR]

Objectives: Aspirin‐exacerbated respiratory disease (AERD) is a chronic respiratory condition characterized by a triad of symptoms: asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory reaction to aspirin and other cyclooxygenase‐1 inhibitors, also known as nonsteroidal anti‐inflammatory drugs. The objective of this review is to provide otolaryngologists with an overview of the pathophysiology, diagnosis, and treatment of this under‐recognized condition. Data sources and methods: Foundational papers on AERD were reviewed, focusing on the clinical otolaryngology and allergy/immunology literature and other high impact journals or trials. Results: AERD results from increased production of pro‐inflammatory leukotrienes and a decrease in production of anti‐inflammatory prostaglandins associated with the dysregulation of multiple enzymes influencing eicosanoid metabolism. Diagnosis hinges on a high index of suspicion, careful history, and confirmatory testing for all three elements. Treatments include endoscopic sinus surgery; topical, inhaled, or oral corticosteroids; aspirin desensitization; leukotriene modifying drugs; and the new class of biologics such as dupilumab. Conclusion: AERD is an under‐recognized disease associated with substantial patient‐reported morbidity. We expect rapid progress in the pathophysiological understanding of this disease and available treatments in the coming decades. Level of evidence: 5 [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to determine whether physiotherapy and counselling students, who represent a future generation of two health professions, have differing views about complementary and alternative medicine (CAM). Methods: In order to determine physiotherapy and counselling students' self‐rated knowledge and beliefs about CAM and the factors which influence that understanding, a modified 10‐item CAM Health Belief Questionnaire was administered across all year groups to physiotherapy students and counselling students at two universities in Perth, Western Australia. The self‐rated paper‐based survey measured knowledge of CAM among physiotherapy and counselling students, evaluation of their beliefs regarding the use of CAM, factors that influence their knowledge and beliefs, and their likelihood of recommending CAM to future patients. Results: A response rate of 96.8% was achieved, with 387 physiotherapy students and 88 counselling students. Moderately positive beliefs about CAM were confirmed in both groups, with mean scores of 42.8/70 for physiotherapy students and 43.3/70 for counselling students. There were no significant differences between the student groups in overall self‐rated knowledge of CAM. The main factors that influenced the students' responses were personal experience for counselling students and scientific evidence for physiotherapy students. Other factors included university training, attitudes of lecturers, tutors and fellow students, cultural background, and opinions of external practitioners. Counselling students were more likely than physiotherapy students to recommend CAM therapies to their future patients. Conclusion: The results from this study demonstrate minimal self‐rated knowledge but moderately positive attitudes towards CAM by both physiotherapy and counselling students. [ABSTRACT FROM AUTHOR]

Accessible summary: Children with learning disabilities often have problems with their eyesight.We tested the eyes of nine children and checked whether they needed glasses or bigger print.We found that when they got what they needed to see better, their behaviour improved.This is important because children with learning disabilities need to be able to see as well as anyone else. Background: Children with identified special educational needs are at higher risk than other children of having visual needs that are not adequately met. This paper evaluates the impact of addressing the visual needs of these children on behaviour and academic achievements in a number of case studies. Method: Nine children (4–11 years of age, from four classrooms), who attended a special school in a medium‐sized town in the UK, took part in the case studies reported here. The children were part of the Special Education Eyecare (SEE) Project. Six of the children were selected because they had unmet visual needs at baseline and required bespoke interventions to meet these needs; the other three children were selected because their visual needs had been met prior to the study and no further adjustments were needed. Repeated direct observations were conducted to assess the impact of the intervention on the children's behaviour in the classroom. The observer was "blind" with regard to the visual needs of the participants. Parents and teachers completed the Strength and Difficulties Questionnaire (SDQ) for each child, before and after the intervention. School files were analysed to assess effects on academic achievement. Findings: Subsequent to the implementation of bespoke visual adjustments, for example prescription of spectacles or changed seating in classroom, significant and sustained changes were observed with regard to the children's behaviour (i.e., increased engagement with peers and/or teachers and decreased off‐task behaviour). Strength and Difficulties Questionnaire scores showed improvements regarding total difficulties, emotional difficulties, hyperactivity and prosocial (kind and helpful) behaviour. Due to highly variable data in school files, the effects on academic achievement were inconclusive. Discussion: The case studies reported here explored changes in behaviour of children with identified special educational needs after their visual needs were met. Findings show a positive overall effect on the behaviour of these children. [ABSTRACT FROM AUTHOR]

Glomerular diseases are leading causes of end‐stage renal disease in children. Tacrolimus is frequently used off‐label in the treatment of glomerular diseases. The effectiveness, safety and pharmacokinetic data of tacrolimus in the treatment of glomerular diseases in children are reviewed in this paper to provide evidence to support its rational use in clinical practice. The remission rates in previously published studies were different. In 19 clinical trials on children with nephrotic syndrome, the overall remission rate was 52.6‐97.6%. In four clinical trials on children with lupus nephritis, the overall remission rate was 81.8‐89.5%. In a pilot study with paediatric Henoch‐Schönlein purpura nephritis patients, the overall remission rate was 100.0%. Infection, nephrotoxicity, gastrointestinal symptoms and hypertension are the most common adverse events. Body weight, age, CYP3A5 genotype, cystatin‐C and daily dose of tacrolimus may have significant effects on the pharmacokinetics of tacrolimus in children with glomerular disease. More prospective controlled trials with long follow‐up are needed to demonstrate definitely the effectiveness, safety and pharmacokinetics of tacrolimus in children with glomerular diseases. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have been revealed to hold great potential for the development of new treatment approaches for various diseases. However, the clinical use of these cells is limited due to their tumorigenic effects. The therapeutic benefits of MSCs are largely dependent on paracrine factors including extracellular vesicles (EVs). EVs are nano‐sized bilayer membrane structures containing lipids, microRNAs and proteins which play key roles in cell‐to‐cell communications. Because of their lower immunogenicity, tumorigenicity, and easier management, EVs have emerged as a new promising alternative to whole‐cell therapy. Therefore, this paper reviews current preclinical studies on the use of EVs derived from human umbilical cord MSCs (hucMSCs) as a therapeutic approach in treatment of several diseases including neurological, cardiovascular, liver, kidney, and bone diseases as well as the cutaneous wound, inflammatory bowel disease, cancers, infertility, and other disorders. [ABSTRACT FROM AUTHOR]

Comprehensive reviews of the clinical characteristics and pathogenesis of Aicardi-Goutières syndrome (AGS), particularly its contextualization within a putative type I interferonopathy framework, already exist. However, recent reports of attempts at treatment suggest that an assessment of the field from a therapeutic perspective is warranted at this time. Here, we briefly summarize the neurological phenotypes associated with mutations in the seven genes so far associated with AGS, rehearse current knowledge of the pathology as it relates to possible treatment approaches, critically appraise the potential utility of therapies, and discuss the challenges in assessing clinical efficacy. WHAT THIS PAPER ADDS: Progress in understanding AGS disease pathogenesis has led to the first attempts at targeted treatment. Further rational therapies are expected to become available in the short- to medium-term. [ABSTRACT FROM AUTHOR]

The standardization of outcome reporting is crucial for interpretation and comparison of studies related to laser treatment of skin disorders. In collaboration with the Cochrane Skin‐Core Outcome Set Initiative (CS‐COUSIN), a procedure has been proposed to find consensus on the most important generic outcome domains (what to measure) for implementation in the international Laser TrEAtment in Dermatology (LEAD) registry. As the first step in the development of a generic outcome set for the LEAD registry, we undertook a systematic review to identify outcomes, outcome measurement instruments, methods and definitions reported in recently published literature of laser treatments for skin disorders. A systematic search was conducted and generated a total of 707 papers. We assessed 150 studies including all types of studies involving laser treatments for the skin. Two researchers independently extracted the type, definition and frequency of all outcomes and used outcome measurement instruments. We identified 105 verbatim outcomes that were categorized into eight domains recommended by the COMET framework: appearance, long‐term effects, physician and patient‐reported physical signs, satisfaction, health‐related quality of life, psychological functioning and adverse events. Heterogeneity in outcome reporting (e.g. categories and outcome measurement instruments) was high, and definitions were insufficiently reported. There was a clear under representation of life impact domains, including satisfaction (23%) quality of life (3%) and psychological functioning (1%). Outcome reporting concerning laser treatments for the skin is heterogeneous. Standardized outcomes are needed for improving evidence synthesis. Results of this review will be used in the next step to reach consensus between stakeholders on the outcome domains to be implemented in the LEAD registry. [ABSTRACT FROM AUTHOR]

Background and objective: End‐stage renal disease (ESRD) affects a multitude of aspects in the patient's daily life, often entailing their own involvement in various aspects of the treatment. Although patient participation is a core health‐care value, what the concept signifies is not yet fully known. The purpose of this paper is to conceptualize patient participation in dialysis care, depicting patients' and health‐care professionals' perspectives. Design: This explorative study employed qualitative interviews and content analysis. Setting and participants: Seven focus group discussions engaging 42 key informants were performed, including patients, staff and managers with experience of dialysis care. Results: In dialysis care, patient participation connotes a sharing of information and knowledge, the learning of and planning of care, including partaking in shared decisions with regards to treatment and management, and being involved in the management of one's own health‐care treatment and/or self‐care activities. Although these attributes were illustrated by all stakeholders, their significance varied: patients suggested that their preferences regarding primary aspects of participation vary, while staff considered patients' performance of dialysis to be the ultimate form of participation. Further, while patients considered multiple ways to execute participation, staff suggested that aspects such as sharing information were a route to, rather than actual, involvement. Conclusions: Without a common understanding to denote the idea of patient participation, staff and patients are exposed to a potential deficit in terms of facilitating patient participation in everyday encounters of dialysis treatment. Further studies and means to serve a mutual understanding are needed. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) are known as a large group of short noncoding RNAs, which structurally consist of 19–22 nucleotides in length and functionally act as one of the main regulators of gene expression in important biological and physiological contexts like cell growth, apoptosis, proliferation, differentiation, movement (cell motility), and angiogenesis as well as disease formation and progression importantly in cancer cell invasion, migration, and metastasis. Among these notable tiny molecules, many studies recently presented the important role of the miR‐193 family comprising miR‐193a‐3p, miR‐193a‐5p, miR‐193b‐3p, and miR‐193b‐5p in health and disease biological processes by interaction with special targeting and signaling, which mainly contribute as a tumor suppressor. Therefore, in the present paper, we review the functional role of this miRNA family in both health and disease conditions focusing on various tumor developments, diagnoses, prognoses, and treatment. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether patients with specific subgingival microbiological profiles benefit more from adjunctive systemic antibiotics. Aims: To answer the question: "What is the clinical benefit in periodontitis patients taking adjunctive systemic antimicrobials to non‐surgical therapy, depending on pre‐treatment detection of periodontopathogenic bacteria?" Materials and methods: A search was conducted in four electronic databases for randomized controlled trials reporting clinical outcomes following adjunctive antibiotic therapy for patients divided by baseline microbiological profiles. Results: The initial search resulted in 643 papers, reduced to five after screening and author contact. Four of these studies were suitable for a fixed effects two‐stage individual participant data meta‐analysis adjusted for baseline data. Collectively, adjunctive amoxicillin and metronidazole yielded superior clinical results (measured as reduction of PPDs) compared to placebo. No significant differences were detected for the effect of adjunctive antibiotics by the detection of Aggregatibacter actinomycetemcomitans on PPDs ≥ 5 mm (WMD = 1.16, 95% CI [−5.37, 7.68], I2 = 37.8%) or other clinical outcomes. All included studies had low risk of bias. Conclusion: There is no evidence to suggest that baseline detection of periodontopathogenic bacteria should be used as criterion for prescribing adjunctive antibiotics, although only limited information on microbial data and specific antimicrobials was available for analysis. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease associated with a high physical and psychological burden. It is a disorder of the infundibular segment of the pilosebaceous unit, characterized by subcutaneous nodules, abscesses, sinus tracts and scar formation on the intertriginous and apocrine‐bearing areas. HS is quite rare in young and prepubertal children. It usually begins after puberty, but several reports of prepubertal HS onset have been described. These cases are strongly linked to hormonal disorders and genetic susceptibility. Specific guidelines for prepubertal patients are still lacking, so further studies are warranted to better delineate a tailored approach. This paper aims to summarize the most significant aspects, as well as the most recent information about the epidemiology, pathogenesis, clinical features, diagnosis, comorbidities and treatment of paediatric HS. In addition, we report our clinical experience in managing HS in a group of eight prepubertal patients based on systemic antibiotics (azithromycin) and zinc oral supplementation. [ABSTRACT FROM AUTHOR]

Summary: Introduction: The incidence rate of psoriasis vulgaris (PSV) coexisting with Juvenile dermatomyositis (JDM) is low. Through our thorough literature search, we found that PSV arising on JDM with superficial fungal infection of facial skin is rarely reported. So, we hereby, report a case of combination of the above three diseases. Meanwhile, we also reviewed the previous literatures aiming at the related basis, clinical manifestation, diagnosis, and treatment of the diseases. Interestingly, of all cases, this case is the only one in which the symptom of muscle weakness preceded the appearance of rash. Case Presentation: A 21‐year‐old man diagnosed with JDM 6 years ago came to our inpatient department due to the appearance of new rash. Skin examination showed some sharply demarcated scaly plaques over the head, neck, torso, and bilateral upper limbs with pruritus and scaling. Histological examination and typical clinical manifestation confirmed the diagnosis of PSV for his new rash. Family history was negative for JDM and PSV. The clear erythema located on his face revealed the existence of superficial fungal infection with the help of fungal fluorescence microscopy. He had marked improvement of his symptoms with the treatment given at our department. In the past 3 months, the patient has been on regular follow‐up at our outpatient department, and his condition is stable at present. Discussion: This paper presents a case of PSV arising on JDM coexisting with superficial fungal infection on the face hoping that this will help clinicians in the better diagnosis of the diseases during literature search. [ABSTRACT FROM AUTHOR]

Background and Aims: Federal, state and local US governments have sought interventions to reduce deaths due to opioid overdoses by increasing the availability of naloxone. The Affordable Care Act (ACA) expanded Medicaid coverage to low‐income, childless adults, potentially giving this group financial access to naloxone. The aims of this paper are: (1) to describe the changes in the amount of Medicaid‐covered naloxone used between 2009 and 2016 and (2) to quantify the differential change in the amount of dispensed naloxone between states that expanded their Medicaid programs and states that did not. Design A quasi‐experimental approach based on states' ongoing choice to expand their Medicaid program to all adults with incomes between 100 and 138% of the federal poverty line (FPL), starting in 2014. As of 2018, 37 states had expanded and 14 states had not. Estimation of the policy impact relies on a difference‐in‐difference method. Setting: US state Medicaid programs. Participants and measurements: Data are from the Medicaid Drug Rebate Program and include all dispensed prescriptions of naloxone through the Medicaid program. State/quarters with fewer than 10 prescriptions are suppressed; n = 1632. Findings Prior to Medicaid expansion, the number of Medicaid‐covered naloxone prescriptions was very similar in expansion and non‐expansion states. On average, states that expanded Medicaid had 78.2 (95% confidence interval = 16.0–140.3, P = 0.02) more prescriptions per year for naloxone compared with states that did not expand Medicaid coverage, a nearly 10 increase over the pre‐expansion years. Medicaid expansion contributed to this growth in Medicaid‐covered naloxone more than other state‐level naloxone policies. Conclusions: Medicaid accounts for approximately a quarter of naloxone sales. Medicaid expansion generated 8.3% of the growth in naloxone units from 2009 to 2016, holding other factors constant. [ABSTRACT FROM AUTHOR]

Chronic ulcerative stomatitis (CUS) is an immune‐mediated disorder characterized by oral erosions and ulcers usually refractory to conventional treatments. The disease often involves middle‐aged and older women with painful lesions sometimes resembling those of erosive oral lichen planus (OLP). The most affected sites are the buccal mucosa, the gingiva and the tongue, but the skin is involved in 22.5% of cases. Histopathologic features in CUS are non‐specific and indistinguishable from those of OLP, with the exception of the presence of a mixed infiltrate composed of lymphocytes and plasma cells. Direct immunofluorescence (DIF) analysis reveals the presence of stratified epithelium‐specific antinuclear antibodies (SES‐ANA) in the lower third of the epithelium. The IgG antibodies detected on DIF are directed against the ∆Np63α isoform of p63 expressed in the nuclei of the epithelial basal cells. A distinguishing feature of CUS is the low response to conventional corticosteroid therapy and the good outcome with hydroxychloroquine at the dosage of 200 mg/day or higher dosages. This paper presents a comprehensive review of CUS and is accompanied by a new case report (the 73rd case) and a proposal for updated diagnostic criteria. [ABSTRACT FROM AUTHOR]

Rodent survival-sacrifice experiments are routinely conducted to assess the tumor-inducing potential of a certain exposure or drug. Because most tumors under study are impalpable, animals are examined at death for evidence of tumor formation. In some studies, the cause of death is ascertained by a pathologist to account for possible correlation between tumor development and death. Existing methods for survival-sacrifice data with cause-of-death information have been restricted to multi-group testing or one-sample estimation of tumor onset distribution and thus do not provide a natural way to quantify treatment effect or dose-response relationship. In this paper, we propose semiparametric regression methods under the popular proportional hazards model for both tumor onset and tumor-caused death. For inference, we develop a maximum pseudo-likelihood estimation procedure using a modified iterative convex minorant algorithm, which is guaranteed to converge to the unique maximizer of the objective function. Simulation studies under different tumor rates show that the new methods provide valid inference on the covariate-outcome relationship and outperform alternative approaches. A real study investigating the effects of benzidine dihydrochloride on liver tumor in mice is analyzed as an illustration. [ABSTRACT FROM AUTHOR]

Epidemiological studies, animal models, and case-control studies indicate maternal immune activation may be an important factor involved in disease expression of autism spectrum disorder (ASD), Tourette syndrome, and obsessive-compulsive disorder (OCD). We report eight children (mean age 6y 6mo [range 4-15y]; six males and two females) referred over a 2-year period with at least one of these neurodevelopmental disorders plus a maternal history of thyroid autoimmunity. Seven of eight children presented with an abrupt onset of neuropsychiatric symptoms (OCD [n=6], tics [n=5], and/or psychosis [n=1]), associated with an autistic or global regression. Four children had a pre-existing diagnosis of ASD. Six presentations were preceded by infection, and symptoms followed a relapsing-remitting course in seven children. All children responded to immunomodulatory treatment as indicated by a reduction in psychiatric symptoms, and seven children were also managed with conventional treatment with additional improvement. We propose that maternal autoimmunity can activate fetal microglia or alter transcription of neurodevelopmental vulnerability and/or immune genes in utero, and is an environmental factor that increases the expression and severity of neurodevelopmental problems, and susceptibility to deteriorations after infectious or stress stimuli. WHAT THIS PAPER ADDS: Maternal thyroid autoimmunity may represent a risk factor for neuropsychiatric disorders in offspring. Atypical neuropsychiatric features in these children may be due to maternal immune activation in utero. [ABSTRACT FROM AUTHOR]

Aim: Most mental disorders have their onset by age 25, disrupting normative vocational engagement. Factors associated with vocational disengagement at first contact with specialist treatment are important for service planning. The aim of this paper was to investigate the association between theoretically important factors and vocational disengagement for youth entering mental health treatment. Methods: A file audit was used to extract vocational data of 145 young people aged 15 to 25 years entering treatment in 2011 at a public youth mental health service in Melbourne, Australia. Comparisons were made across three specialist programs for: psychosis (n = 50), mood disorders (n = 52) and borderline personality pathology (n = 43). Individual characteristics were entered into univariate and multivariate logistic regressions to investigate their associations with vocational disengagement. Results: Educational disengagement was associated with being older (OR = 4.38, P = 0.004) and not living with parents (OR = 2.87, P = 0.038). Unemployment and being NEET (Not in Education, Employment or Training) were both associated with not having commenced tertiary education (OR = 0.23, P = 0.022; OR = 0.05, P = 0.002; respectively). Being NEET was also associated with being older (OR = 6.18, P = 0.004). Primary diagnostic grouping was not associated with vocational disengagement, once accounting for other factors. Conclusions: The likelihood of vocational disengagement did not differ across disorder groups, implying that intervention should be "transdiagnostic" and might best target education first, specifically post‐secondary qualifications. Other domains or variables not measured in this study are also likely to be important, and this might include young people's support systems and symptom severity. Qualitative studies may be useful for exploring further factors relevant to vocational engagement. [ABSTRACT FROM AUTHOR]

A failure to maintain improvement achieved during acute treatment, followed by a "revolving door syndrome," is a common phenomenon in eating disorders (EDs). As a result, many patients develop a chronic course that is difficult to treat. To target these difficulties, we established a novel rehabilitation treatment model in Israel for patients with severe and enduring EDs, based on the "recovery theory" in mental health treatment. This paper describes the process of conceiving this model and specifies the components of this rehabilitation house, "Zeida Laderech" (Provisions for the Journey), that aims to provide a home‐like environment, while assisting in developing a healthy and balanced lifestyle. Finally, the model is discussed in light of other residential programs established in the world. With the hope to improve the overall prognosis of individuals with EDs, it is suggested that the similar programs and ongoing innovation will continue to emerge internationally. [ABSTRACT FROM AUTHOR]

The aim of this case study is to illustrate the importance of collaborative care as part of Maudsley Anorexia Nervosa Treatment for Adults (MANTRA). Mothers are often at the foreground of providing support within the family. However, fathers have the potential to play a profound role. In this paper, we describe a patient with anorexia nervosa treated with the MANTRA. The formulation of this case included autistic spectrum traits in both the father and daughter leading to social isolation. We describe how the family members were engaged into treatment and how paternal support was used to promote social connection and an improved quality of life in the daughter. Some details of the case have been altered to maintain confidentiality. [ABSTRACT FROM AUTHOR]

In eating disorders, the denial of the illness is a central phenomenon. In the most severe forms of anorexia, compulsory treatment may be necessary. The professional acceptance of involuntary treatment is controversial due to the fact that the autonomy of the patient is juxtaposed with the obligation of the health care practitioner to save lives. This paper discusses the major practical and ethical considerations surrounding this controversy. In addition, case vignettes are used to illustrate various strategies to diminish client resistance and enhance motivation toward treatment. Involving the family is nearly always essential for the treatment of patients with eating disorders. In some cases, parental consultation (i.e., treatment without the client) can also be an option. Home visits, though rarely used, can reframe the therapeutic relationship and provide information about family functioning. In general, a lower level of treatment coercion can be achieved through transparent client‐parent and client‐therapist communication. [ABSTRACT FROM AUTHOR]

We want to discuss antivenom use in snakebite clinical practice guidelines. Coronial reviews in Victoria of two cases of snakebite envenomation, one described in detail below, prompted us to submit this paper for a wider audience and debate. Venom and antivenom levels were measured in the case detailed below, but not in the other. The coroner received conflicting and varied advice from experts regarding the dose of antivenom. The Victorian Department of Health and Human Services and the Australasian College for Emergency Medicine were instructed to review snakebite management guidelines, particularly with respect to antivenom dosage. The discussion that took place among medical experts led to considerable media attention. We discuss the potential fallout when there is no consensus among medical experts. [ABSTRACT FROM AUTHOR]

Background: Behavioural emergencies (BEs) are complex situations in the emergency department (ED) setting. Treatment decisions always must be made within a limited time and are based on incomplete patient data. As a result of the urgency and complexity, patients often are exposed to increased risk of harm. Aim: The aim of this paper is to describe the prescribing patterns and adverse events (AEs) associated with parenteral sedation for the management of BEs in Australian EDs. Methods: Ten Australian EDs enrolled a convenience sample of adult patients (aged ≥18 years) requiring parenteral sedative medication for BEs. Data were collected prospectively between March 2015 and April 2017 using a designated case report form. Results: In all, 564 cases were enrolled in this study. Incomplete cases (n = 17; 3%) were excluded. Of the 547 remaining cases, 63% were male and the median age was 34 years (range 18–95 years). Approximately half the patients (n = 230; 42.1%) required mechanical restraint and parenteral sedation to manage their BEs. Intramuscular monotherapy was administered in most cases (n = 390; 71.3%). The main sedative medications used as monotherapy were droperidol (n = 381; 69.7%), midazolam (n = 54; 9.9%) and olanzapine (n = 26; 4.8%). The most common combination therapy was midazolam + droperidol (n = 36; 6.6%). The incidence of AEs from sedative administration was 13.5%. No deaths or irreversible AEs were reported. Conclusions: Overall, the participating EDs provided safe pharmacological management for BEs. AEs following parenteral sedation are common, although serious AEs are rare. Because all patients receiving parenteral sedation for BEs are at risk of AEs, ongoing monitoring of vital signs after parenteral sedation should be a standard protocol in all EDs. [ABSTRACT FROM AUTHOR]

Background: Time trends of lung cancer prevalence and mortality are the result of three competing processes: changes in the incidence rate, stage-specific survival, and ascertainment at early stages. Improvements in these measures act concordantly to improve disease-related mortality, but push the prevalence rate in opposite directions making a qualitative interpretation difficult. The goal of this paper is to evaluate the relative contributions of these components to changes in lung cancer prevalence and mortality.Methods: Partitioning of prevalence and mortality trends into their components using SEER data for 1973-2013.Results: The prevalence of lung cancer increases for females and decreases for males. In 1998, the former was due to increased incidence (45%-50% of total trend), improved survival (40%-45%), and increased ascertainment at early stages (10%-15%). In males, a rapidly declining incidence rate overpowered the effects of survival and ascertainment resulting in an overall decrease in prevalence over time. Trends in lung cancer mortality are determined by incidence during 1993-2002 with noticeable contribution of survival after 2002.Conclusion: Lung cancer incidence was the main driving force behind trends in prevalence and mortality. Improved survival played essential role from 2000 onwards. Trends in stage ascertainment played a small but adverse role. Our results suggest that further improvement in lung cancer mortality can be achieved through advances in early stage ascertainment, especially for males, and that in spite of success in treatment, adenocarcinoma continues to exhibit adverse trends (especially in female incidence) and its role among other histology-specific lung cancers will increase in the near future. [ABSTRACT FROM AUTHOR]

Equal randomization has been a popular choice in clinical trial practice. However, in trials with heterogeneous variances and/or variable treatment costs, as well as in settings where maximization of every trial participant's benefit is an important design consideration, optimal allocation proportions may be unequal across study treatment arms. In this paper, we investigate optimal allocation designs minimizing study cost under statistical efficiency constraints for parallel group clinical trials comparing several investigational treatments against the control. We show theoretically that equal allocation designs may be suboptimal, and unequal allocation designs can provide higher statistical power for the same budget or result in a smaller cost for the same level of power. We also show how optimal allocation can be implemented in practice by means of restricted randomization procedures and how to perform statistical inference following these procedures, using invoked population-based or randomization-based approaches. Our results provide further support to some previous findings in the literature that unequal randomization designs can be cost efficient and can be successfully implemented in practice. We conclude that the choice of the target allocation, the randomization procedure, and the statistical methodology for data analysis is an essential component in ensuring valid, powerful, and robust clinical trial results. [ABSTRACT FROM AUTHOR]

The Mantel-Haenszel (MH) method has been used for decades to synthesize data obtained from studies that compare two interventions with respect to a binary outcome. It has been shown to perform better than the inverse-variance method or Peto's odds ratio when data is sparse. Network meta-analysis (NMA) is increasingly used to compare the safety of medical interventions, synthesizing, eg, data on mortality or serious adverse events. In this setting, sparse data occur often and yet there is to-date, no extension of the MH method for the case of NMA. In this paper, we fill this gap by presenting a MH-NMA method for odds ratios. Similarly to the pairwise MH method, we assume common treatment effects. We implement our approach in R, and we provide freely available easy-to-use routines. We illustrate our approach using data from two previously published networks. We compare our results to those obtained from three other approaches to NMA, namely, NMA with noncentral hypergeometric likelihood, an inverse-variance NMA, and a Bayesian NMA with a binomial likelihood. We also perform simulations to assess the performance of our method and compare it with alternative methods. We conclude that our MH-NMA method offers a reliable approach to the NMA of binary outcomes, especially in the case or sparse data, and when the assumption of methodological and clinical homogeneity is justifiable. [ABSTRACT FROM AUTHOR]

Summary: Background: Direct‐acting anti‐viral therapy (DAA) has transformed hepatitis C virus (HCV) care, particularly in patients with decompensated cirrhosis. However, their impact on hepatocellular carcinoma (HCC) remains unclear. Aim: To use a national registry of patients with advanced liver disease to explore the relationship between DAA therapy and HCC. Methods: All patients with de novo HCC post DAA therapy were frequency matched with patients who did not develop HCC. Demographic, clinical and laboratory data were obtained. Cross‐sectional imaging and multidisciplinary team reports were reviewed for dates of HCC diagnosis and HCC progression. Patients were categorised by treatment outcome and time of HCC development. Data were examined by multivariable analysis and Kaplan‐Meier estimation. Results: Eighty patients with HCC were compared with 165 patients without HCC, treated between June 2014 and September 2015. Mean follow‐up from start of DAA therapy was 32.4 months. Twenty‐eight patients were diagnosed with early HCC (within 6 months of therapy) and 52 presented late. Baseline nonmalignant lesions (HR: 1.99), thrombocytopaenia (HR: 1.59) and diabetes (HR: 1.68) increased likelihood of HCC. Response to therapy was reduced in patients who developed liver cancer (SVR in patients with HCC = 54/80 (68%), SVR in patients without HCC = 143/165 (87%), P < 0.001, OR: 3.13, 95% CI: 1.64‐5.99). We found no difference between tumour size, progression or survival between viraemic and nonviraemic patients. Conclusion: There is no alteration in prognosis or cancer progression following HCC development after HCV treatment. However, baseline nonmalignant liver lesions, diabetes and thrombocytopaenia increase the risk of HCC, and HCC is associated with a decreased SVR rate. Linked Content This article is linked to Hollande and Pol paper. To view this article, visit https://doi.org/10.1111/apt.15328. [ABSTRACT FROM AUTHOR]

It is well known that the treatment effect of a molecularly targeted agent (MTA) may vary dramatically, depending on each patient's biomarker profile. Therefore, for a clinical trial evaluating MTA, it is more reasonable to evaluate its treatment effect within different marker subgroups rather than evaluating the average treatment effect for the overall population. The marker-stratified design (MSD) provides a useful tool to evaluate the subgroup treatment effects of MTAs. Under the Bayesian framework, the beta-binomial model is conventionally used under the MSD to estimate the response rate and test the hypothesis. However, this conventional model ignores the fact that the biomarker used in the MSD is, in general, predictive only for the MTA. The response rates for the standard treatment can be approximately consistent across different subgroups stratified by the biomarker. In this paper, we proposed a Bayesian hierarchical model incorporating this biomarker information into consideration. The proposed model uses a hierarchical prior to borrow strength across different subgroups of patients receiving the standard treatment and, therefore, improve the efficiency of the design. Prior informativeness is determined by solving a "customized" equation reflecting the physician's professional opinion. We developed a Bayesian adaptive design based on the proposed hierarchical model to guide the treatment allocation and test the subgroup treatment effect as well as the predictive marker effect. Simulation studies and a real trial application demonstrate that the proposed design yields desirable operating characteristics and outperforms the existing designs. [ABSTRACT FROM AUTHOR]

The literature on causal effect estimation tends to focus on the population mean estimand, which is less informative as medical treatments are becoming more personalized and there is increasing awareness that subpopulations of individuals may experience a group-specific effect that differs from the population average. In fact, it is possible that there is underlying systematic effect heterogeneity that is obscured by focusing on the population mean estimand. In this context, understanding which covariates contribute to this treatment effect heterogeneity (TEH) and how these covariates determine the differential treatment effect (TE) is an important consideration. Towards such an understanding, this paper briefly reviews three approaches used in making causal inferences and conducts a simulation study to compare these approaches according to their performance in an exploratory evaluation of TEH when the heterogeneous subgroups are not known a priori. Performance metrics include the detection of any heterogeneity, the identification and characterization of heterogeneous subgroups, and unconfounded estimation of the TE within subgroups. The methods are then deployed in a comparative effectiveness evaluation of drug-eluting versus bare-metal stents among 54 099 Medicare beneficiaries in the continental United States admitted to a hospital with acute myocardial infarction in 2008. [ABSTRACT FROM AUTHOR]

Introduction and Aims: There has been significant recent investment in new medications for opioid use disorder, including buprenorphine depot injections. Patients and professionals need good quality, independent information on medications to help them make informed treatment decisions. This paper aims to understand patients' information needs and preferences in relation to buprenorphine depot injections.Design and Methods: Semi-structured qualitative interviews were conducted with 36 people using opioids (26 men, 10 women; 24-63 years). Twelve participants were currently prescribed daily oral methadone; 12 were currently prescribed daily oral buprenorphine; and 12 were using heroin and not in treatment. Interviews were transcribed, coded and analysed via Iterative Categorisation.Results: Participants asked many questions about depot buprenorphine injections. These related to: (i) medication purpose and availability; (ii) pharmacology; (iii) evidence base and effectiveness; (iv) safety and side effects; (v) administration and dosing; and (vi) reducing and ending treatment. Additionally, participants expressed their information preferences in terms of (i) 'format' and (ii) 'source'. Specifically, they wanted printed, verbal and electronic materials provided by people in authority, particularly patients who had already had the medication.Discussion and Conclusions: All potential patients should be offered accessible information on depot buprenorphine to enable them to consider their options and participate meaningfully in treatment decision making. We recommend that further qualitative research is undertaken to produce informative video material that describes patient experiences of receiving depot buprenorphine. This should help to balance biomedical knowledge with lay knowledge, so facilitating more informed discussions when decisions about depot buprenorphine treatment are made. [ABSTRACT FROM AUTHOR]

Summary: When a candidate predictive marker is available, but evidence on its predictive ability is not sufficiently reliable, all‐comers trials with marker stratification are frequently conducted. We propose a framework for planning and evaluating prospective testing strategies in confirmatory, phase III marker‐stratified clinical trials based on a natural assumption on heterogeneity of treatment effects across marker‐defined subpopulations, where weak rather than strong control is permitted for multiple population tests. For phase III marker‐stratified trials, it is expected that treatment efficacy is established in a particular patient population, possibly in a marker‐defined subpopulation, and that the marker accuracy is assessed when the marker is used to restrict the indication or labelling of the treatment to a marker‐based subpopulation, ie, assessment of the clinical validity of the marker. In this paper, we develop statistical testing strategies based on criteria that are explicitly designated to the marker assessment, including those examining treatment effects in marker‐negative patients. As existing and developed statistical testing strategies can assert treatment efficacy for either the overall patient population or the marker‐positive subpopulation, we also develop criteria for evaluating the operating characteristics of the statistical testing strategies based on the probabilities of asserting treatment efficacy across marker subpopulations. Numerical evaluations to compare the statistical testing strategies based on the developed criteria are provided. [ABSTRACT FROM AUTHOR]

Down syndrome disintegrative disorder (DSDD) is an increasingly identified condition characterized by cognitive decline, autistic characteristics, insomnia, catatonia, and psychosis in adolescents and young adults with Down syndrome. Previously we reported a higher rate of autoimmune thyroid disease in these patients compared with unaffected individuals with Down syndrome. We therefore hypothesized DSDD may in some cases be immune-mediated. Here we report four cases of DSDD treated with immunotherapy. Families were interviewed retrospectively for symptoms of cognitive decline, autism, catatonia, psychosis, and insomnia before and after treatment, using established scales where possible. Medical records were reviewed for evaluations and treatment. All four patients received intravenous immunoglobulin with or without additional immunotherapy. Significant improvements were seen in catatonia, insomnia, autistic features, cognition, and psychosis. In this small case series of patients with autoimmunity, core symptoms of DSDD improved significantly after immunotherapy. This supports the hypothesis that, in some patients, DSDD is immune-mediated. Immunotherapy should be considered in the treatment of DSDD, particularly in patients with a history of autoimmunity. WHAT THIS PAPER ADDS: Immunotherapy may improve symptoms of catatonia, insomnia, autism severity, cognitive decline, and psychosis in Down syndrome disintegrative disorder. [ABSTRACT FROM AUTHOR]

Summary: Background: Thyroid eye disease (TED) is an autoimmune inflammatory disease that can be disfiguring and potentially sight threatening. Suppression of inflammation in active disease can reduce the risk of visual loss and limit long‐term sequelae. Current management involves inflammation suppression using glucocorticoids. The aim of this study was to evaluate the efficacy of early disease intervention with targeted immunomodulatory therapy to alter disease course. This paper reports the efficacy of low‐dose rituximab in reducing clinical activity in TED in a small population. Methods: A retrospective audit of consecutive patients with active TED managed primarily with a 100 mg rituximab infusion. Further glucocorticoid or steroid‐sparing agents were prescribed if clinically indicated. Clinical activity score, VISA overall severity score and Oxford Quality of Life score were recorded at each visit as well as TSH receptor antibody levels (TRAb), B cell subsets and adverse reactions. Results: Twelve patients had mean follow‐up of 6.3 months. Clinical activity scores significantly decreased (mean score 5.08 to 1.58; P < 0.001), VISA overall severity scores reduced by 50% from 12 to 6, P < 0.001 and the mean cumulative dose of IV methylprednisolone was 2.3 g. 100 mg rituximab induced significant CD19+ B cell depletion (n = 8, P < 0.001). There was no significant reduction in serum TRAb (n = 8, P = 0.06). A transient infusion‐related rash was the only adverse effect, n = 4. QoL scores did not differ markedly before and after treatment. Conclusion: Low‐dose rituximab is an efficacious, well‐tolerated and safe treatment for active TED; reducing disease activity and allowing reduced administration of systemic steroid. [ABSTRACT FROM AUTHOR]

Vocal fold nodules present the voice clinic team with a number of clinical dilemmas which are not as simple as previously thought. The definition, aetiology, prevalence and diagnosis are all poorly understood. Furthermore, treatment evidence for both behavioural and surgical approaches is weak. This paper reviews the published evidence pertaining to all of these aspects. Specific areas of uncertainty that remain include poorly defined nomenclature, the natural history of paediatric vocal nodules, the establishment of criteria to measure successful treatment, optimal configuration of speech therapy regimens and the rationale for surgical intervention. The authors suggest the development of evidence‐based guidelines for UK practice. [ABSTRACT FROM AUTHOR]

This article serves as an introduction to the special issue on Identification, Classification, and Treatment of Reading and Language Disabilities in Spanish‐speaking English Learners. The article explains the driving forces behind the need for the special issue, the global nature of linguistic diversity, and provides an overview of the five papers that comprise the special issue. [ABSTRACT FROM AUTHOR]

Aim: The aim of this network meta‐analysis (NMA) was to compare the efficacy of different oral hygiene products for chemical biofilm control, in 6‐month home‐use, randomized clinical trials (RCTs), in terms of changes in gingival index (GI). Material and Methods: Six‐month RCTs assessing GI were identified and screened for inclusion. Relevant information was extracted, and quality and potential risk of bias were estimated. Mean differences between baseline and end were calculated to obtain standardized mean differences (SMDs). NMA protocols were applied to assess direct and indirect comparisons among products using Löe & Silness GI, modified GI and gingival severity index. Results: Fifty‐three papers were included, 19 studies for mouth rinses, 32 for dentifrices, comprising data from 5,775 and 2,682 subjects, respectively. When ranking treatments, similar results were observed for all tested dentifrices, with the lowest effect observed for sanguinarine and baking soda. For mouth rinses, essential oils, triclosan–copolymer, chlorhexidine (at concentrations ≥ 0.10%) and cetylpyridinium chloride (>0.05%) demonstrated the greatest effect. Conclusion: Although NMA revealed significant differences when comparing placebo versus some active agents, when comparing among active agents, no differences were found for dentifrices, while mouth rinses containing essential oils showed the greatest effect on GI scores. [ABSTRACT FROM AUTHOR]

Background: Leprosy or Hansen's disease is a chronic infection caused by Mycobacterium leprae (M. leprae) or Mycobacterium lepromatosis (M. lepromatosis). In Europe, most of the leprosy cases are imported. However, occasionally a case is diagnosed in one of the old endemic foci. Leprosy is often not suspected because it is no longer emphasized in the medical curricula. Attention shifted from leprosy to tuberculosis and human immunodeficiency virus infections in the late 20th century, whereby the WHO leprosy programme was toned down in the conviction that leprosy was all but eliminated. The result of unawareness is a harmful doctor's delay. Material and methods: This paper focusses on clinical diagnosis, complications and treatment based on literature and experience. Results: It mentions the value of laboratory tests in classification, follow‐up and detection of relapses. It discusses the etiopathology. Conclusion: This is a position statement. [ABSTRACT FROM AUTHOR]

Meibomian gland dysfunction is one of the most common ocular disorders encountered by ophthalmologists and is the leading cause of evaporative dry eye. The disease causes significant morbidity in the population such that patients seek treatment. Multiple clinical studies on pharmacological and mechanical interventions for the treatment of meibomian gland dysfunction have been evaluated. However, there is limited comparative clinical evidence for the effectiveness of these interventions. This review paper aims to report the clinical evidence for pharmaceutical interventions for meibomian gland dysfunction in order to guide clinicians in the management of the disease. [ABSTRACT FROM AUTHOR]

The article lists several research papers to be published in 2017 issue which include topics like selective neutralization of the serpin Protease Nexin-1 by a specific monoclonal antibody; Heavy menstrual bleeding on rivaroxaban; and Monoclonal B cell lymphocytosis and hypogammaglobulinemia.

LINKED CONTENT: This article is linked to Cho et al papers. To view these articles, visit https://doi.org/10.1111/apt.17255 [ABSTRACT FROM AUTHOR]

Objectives The fate of all manuscripts rejected from the journal Clinical Otolaryngology ( CO) over a three-year period was investigated. The aim was to review publication rate, delay and the impact factors of the journals that the papers went on to be published in. Design In total, 917 papers were rejected from CO between 2011 and 2013. The fate of these manuscripts was determined by searching for the corresponding author's surname, and if necessary keywords from the manuscript title, in both PubMed and Google Scholar. Main outcome measures The main outcome measures recorded were as follows: the subsequent publication of the article, delay to publication and journal of publication. Results In all, 511 papers were subsequently published in journals, representing 55.7% of all rejected manuscripts. The average delay was 15.1 months (standard deviation [ sd] = 8.8). The impact factor of CO was found to be higher than the average of the journals that accepted the rejected manuscripts in all 3 years. Only 41 (8%) papers were published in journals with a higher impact factor than CO. Of all subsequently accepted manuscripts, 60 (11.7%) were found only on Google Scholar (and not on PubMed). Conclusions Rejection from CO certainly does not prevent subsequent publication, although the papers tend to be published after a lengthy delay and in journals with a lower impact factor than CO. When performing literature searches, it is important to search more than one database to ensure as many of the relevant articles are found as possible. [ABSTRACT FROM AUTHOR]