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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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.

Objective Positive psychotherapy (PPT) stems from the positive psychology movement and is a multicomponent model promoting therapeutic change by developing engagement, pleasure, and meaning. There is some evidence it is effective for depression. PPT is recommended as a flexible model that can be applied to other patient groups alongside other treatments approaches. However, it remains unclear which of the many components are applied. The study aimed to identify how PPT is applied in mental health care. Method We systematically searched online databases, including Medline, Embase, PsycINFO, British Nursing Index, Cumulative Index of Nursing and Applied Health, and Cochrane registers (CENTRAL), and completed complementary hand and citation searches. Narrative synthesis was used for analysis. Results A total of 12 papers (from 9 studies) widely applied some PPT components (e.g., blessings journal, character strengths) and scarcely applied others (e.g., satisficing plan or family strengths tree). However, papers poorly described the intervention and rationale for applying components. Conclusion Given the lack of rationale for applying PPT, further research is needed to establish which components are acceptable and feasible for use in different patient groups and settings. [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]

Background The incidence of cardiac arrest and cardiopulmonary resuscitation continues to increase worldwide largely due to greater awareness of the symptoms of cardiac events and increased attention to cardiopulmonary resuscitation training in the community. Globally, predicted survival rates after cardiopulmonary resuscitation have remained at 10% for decades and although patient outcome remains unpredictable, there is a positive trend in life expectancy. For a resuscitation attempt to be classed as successful, not only survival but also quality of life has to be evaluated. Aim The aim of this review was to examine literature that explores the quality of life ( QOL) for survivors' after CPR and the influence cognitive impairment, anxiety, depression and post-traumatic stress disorder ( PTSD) has had on their QOL. Review methods This review follows Whittemore and Knafl's framework for an integrative literature review. Electronic databases EBSCO, Ovid, PubMed and EMBASE were searched. After application of the inclusion and exclusion criteria, thirty-six papers published from January 2000 to June 2015 were included in this review. Results These papers represent a broad spectrum of research evaluating quality of life for survivors of cardiopulmonary resuscitation. The heterogeneous research methods and vast number of different research tools make it challenging to compare the findings. The majority of papers concluded that quality of life for survivors of cardiac arrest and cardiopulmonary resuscitation was generally acceptable. However, studies also described survivors' experience of anxiety, depression, post-traumatic stress and cognitive dysfunction. Conclusion A majority of papers reported an acceptable quality of life if the patient survived to hospital discharge. The heterogeneity in quantitative papers was noticeable and indicates a marked variance in patient outcomes. This review highlights the absence of specialized tools used to investigate survivors' experience of the event. Further exploration of the impact cardiopulmonary resuscitation has on the individual may improve ongoing rehabilitation and quality of life levels for survivors. [ABSTRACT FROM AUTHOR]

Background and Aims Despite decades of research on co-occurring smoking and depression, cessation rates remain consistently lower for depressed smokers than for smokers in the general population, highlighting the need for theory-driven models of smoking and depression. This paper provides a systematic review with a particular focus upon psychological states that disproportionately motivate smoking in depression, and frame an incentive learning theory account of smoking-depression co-occurrence. Methods We searched PubMed, Scopus, PsychINFO and CINAHL to December 2014, which yielded 852 papers. Using pre-established eligibility criteria, we identified papers focused on clinical issues and motivational mechanisms underlying smoking in established, adult smokers (i.e. maintenance, quit attempts and cessation/relapse) with elevated symptoms of depression. Two reviewers determined independently whether papers met review criteria. We included 297 papers in qualitative synthesis. Results Our review identified three primary mechanisms that underlie persistent smoking among depressed smokers: low positive affect, high negative affect and cognitive impairment. We propose a novel application of incentive learning theory which posits that depressed smokers experience greater increases in the expected value of smoking in the face of these three motivational states, which promotes goal-directed choice of smoking behavior over alternative actions. Conclusions The incentive learning theory accounts for current evidence on how depression primes smoking behavior and provides a unique framework for conceptualizing psychological mechanisms of smoking maintenance among depressed smokers. Treatment should focus upon correcting adverse internal states and beliefs about the high value of smoking in those states to improve cessation outcomes for depressed smokers. [ABSTRACT FROM AUTHOR]

Introduction: Substance use is an important risk factor for HIV, with both concentrated in certain vulnerable and marginalized populations. Although their management differs, there may be opportunities to integrate services for substance use and HIV. In this paper we systematically review evidence from studies that sought to integrate care for people living with HIV and substance use problems. Methods: Studies were included if they evaluated service integration for substance use and HIV. We searched multiple databases from inception until October 2015. Articles were screened independently by two reviewers and assessed for risk of bias. Results and discussion: 11,057 records were identified, with 7616 after removal of duplicates. After screening titles and abstracts, 51 met the inclusion criteria. Integration models were categorized by location (HIV, substance use and other facilities), level of integration from mirco (integrated care delivered to individuals) to macro (system level integrations) and degree of integration from least (screening and counselling only) to most (care for HIV, substance use and/or other illnesses at the same facility). Most reported descriptive or cohort studies; in four randomized control trials integrated activities improved patient outcomes. There is potential for integrating services at all facility types, including mobile health services. While services offering screening only can achieve synergies, there are benefits from delivering integrated treatment for HIV and substance use, including ease of referral to other mental health and social services. Conclusions: Our review used a wide range of databases and conference archives to increase representation of papers from low- and middle-income countries. Limitations include the overrepresentation of studies from the United States, and the descriptive nature of the majority of papers. The evidence reviewed shows that greater integration offers important benefits in both patient and service outcomes but further research and outcome reporting is needed to better understand innovative and holistic care models at the complex intersection of substance use and HIV services. [ABSTRACT FROM AUTHOR]

Background: There is limited literature around peer research in dementia. This study aims to identify the benefits, the risks and the practical challenges and to develop a model of good practice in peer research with people with dementia.Methods: We searched on PsycInfo, PubMed and Google Scholar for empirical investigations or discussion papers on peer research. Given the limited literature in the field of dementia, we included studies with groups who share similar demographics (older people), experience of stigma (mental health service users) and exclusion from research (people with learning disabilities). We applied no restrictions on language and publication date.Analysis: We identified three themes: the potential benefits, the potential risks and the practical challenges of peer research. We developed a model of good practice. The European Working Group of People with Dementia reviewed our paper and added to our findings.Results: We included seven papers. Potential benefits of peer research included enriched data and empowering people with dementia. Potential risks included power differentials between researchers and issues of representativeness. The practical issues for good practice included the training of peer researchers, defining involvement and roles, working with cognitive impairment and considering resource implications. The European Working Group of People with Dementia emphasised the importance of equality issues.Conclusion: Involving people with dementia in peer research can generate several benefits, including empowerment and opportunities for inclusion for the peer researchers and the research participants living with dementia, challenging academics' traditional views on research processes and gathering enhanced research data. There remains a need for further research on the impact of peer research in dementia studies. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 46 issue‐toc‐levels 0 issue‐pricelist‐year 2016 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2016 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2016 article‐registration‐date‐month 9 article‐registration‐date‐day 17 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2016_Article_121.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Background: We conducted a clinical study that tested the effect of suppressive treatment with the botanical product Gene‐Eden‐VIR/Novirin on genital herpes. Our previous paper showed that the treatment decreased the number of genital herpes outbreaks without any side effects. It also showed that the clinical effects of Gene‐Eden‐VIR/Novirin are mostly better than those reported in the studies that tested acyclovir, valacyclovir, and famciclovir. The current paper reports the effect of suppressive treatment with Gene‐Eden‐VIR/Novirin on the duration of outbreaks, in severe and mild genital herpes cases. Methods: The framework was a retrospective chart review. The population included 137 participants. The treatment was 1–4 capsules per day. The duration of treatment was 2–48 months. The study included three controls: baseline, no‐treatment, and dose–response. Results: The treatment decreased the duration of outbreaks in 87 % of participants and decreased the mean duration of outbreaks from 8.77 days and 6.7 days in the control groups to 2.87 days in the treatment group (P < 0.001, both groups). All participants reported no adverse experiences. Conclusions: This paper shows that suppressive treatment with Gene‐Eden‐VIR/Novirin decreased the duration of genital herpes outbreaks, in both severe and mild cases, without any side effects. Based on the results reported in this and our previous paper, we recommend suppressive treatment with Gene‐Eden‐VIR/Novirin as a natural alternative to both suppressive and episodic treatments with current drugs, in both severe and mild genital herpes cases. Trial registration ClinicalTrials.gov NCT02715752 Registered 17 March 2016 Retrospectively Registered [ABSTRACT FROM AUTHOR]

Background: We conducted a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on genital herpes. Our previous paper showed that the treatment decreased the number of genital herpes outbreaks without any side effects. It also showed that the clinical effects of Gene-Eden-VIR/Novirin are mostly better than those reported in the studies that tested acyclovir, valacyclovir, and famciclovir. The current paper reports the effect of suppressive treatment with Gene-Eden-VIR/Novirin on the duration of outbreaks, in severe and mild genital herpes cases. Methods: The framework was a retrospective chart review. The population included 137 participants. The treatment was 1-4 capsules per day. The duration of treatment was 2-48 months. The study included three controls: baseline, no-treatment, and dose-response. Results: The treatment decreased the duration of outbreaks in 87 % of participants and decreased the mean duration of outbreaks from 8.77 days and 6.7 days in the control groups to 2.87 days in the treatment group (P < 0.001, both groups). All participants reported no adverse experiences. Conclusions: This paper shows that suppressive treatment with Gene-Eden-VIR/Novirin decreased the duration of genital herpes outbreaks, in both severe and mild cases, without any side effects. Based on the results reported in this and our previous paper, we recommend suppressive treatment with Gene-Eden-VIR/Novirin as a natural alternative to both suppressive and episodic treatments with current drugs, in both severe and mild genital herpes cases. Trial registration ClinicalTrials.gov NCT02715752 Registered 17 March 2016 Retrospectively Registered [ABSTRACT FROM AUTHOR]

Background Trans-oral surgical and non-surgical management options for oropharyngeal squamous cell carcinoma ( OPSCC) appear to offer similar survival outcomes. Functional outcomes, in particular swallowing, have become of increasing interest in the debate regarding treatment options. Contemporary reviews on function following treatment frequently include surrogate markers and limit the value of comparative analysis. Objectives of review A systematic review was performed to establish whether direct comparisons of swallowing outcomes could be made between trans-oral surgical approaches (trans-oral laser microsurgery ( TLM)/trans-oral robotic surgery ( TORS)) and (chemo)radiotherapy ((C) RT). Type of review Systematic review. Search strategy MEDLINE, Embase and Cochrane databases were interrogated using the following Me SH terms: antineoplastic protocols, chemotherapy, radiotherapy, deglutition disorders, swallowing, lasers, and trans-oral surgery. Evaluation method Two authors performed independent systematic reviews and consensus was sought if opinions differed. The WHO ICF classification was applied to generate analysis based around body functions and structure, activity limitations and participation restriction. Results Thirty-seven citations were included in the analysis. Twenty-six papers reported the outcomes for OPSCC treatment following primary (C) RT in 1377 patients, and 15 papers following contemporary trans-oral approaches in 768 patients. Meta-analysis was not feasible due to varying methodology and heterogeneity of outcome measures. Instrumental swallowing assessments were presented in 13/26 (C) RT versus 2/15 TLM/ TORS papers. However, reporting methods of these studies were not standardised. This variety of outcome measures and the wide-ranging intentions of authors applying the measures in individual studies limit any practical direct comparisons of the effects of treatment on swallowing outcomes between interventions. Conclusions From the current evidence, no direct comparisons could be made of swallowing outcomes between the surgical and non-surgical modalities. Swallowing is a multidimensional construct, and the range of assessments utilised by authors reflects the variety of available reporting methods. The MD Anderson Dysphagia Inventory is a subjective measure that allows limited comparison between the currently available heterogeneous data, and is explored in detail. The findings highlight that further research may identify the most appropriate tools for measuring swallowing in patients with OPSCC. Consensus should allow their standardised integration into future studies and randomised control trials. [ABSTRACT FROM AUTHOR]

Introduction Between September 2012 and December 2015, a series of national and regional consultations, aimed at resolving a persistent dynamic of conflict between law enforcement agencies (LEAs) and civil society organizations (CSOs) working on issues of access to HIV services in high-priority countries for people who use drugs have been organized by the HIV/AIDS Section of the United Nations Office on Drugs and Crime, the Joint United Nations Programme on HIV/AIDS, the Law Enforcement and HIV Network (LEAHN) and other international organizations. The aim of these consultations has been to understand, at a national and regional level, the key points of tension between police and CSOs and how to overcome these tensions to enhance access to and uptake of services by key populations, including people who inject drugs, sex workers, men who have sex with men and transgenders. This commentary briefly describes the methods, process, content and key outcomes of these consultations held across diverse number of countries and regions, including Africa, South East Asia, South Asia, Central Asia, Eastern Europe and Latin America. Discussion While the context varies, this paper highlights that there are commonalities that drive a persistent dynamic of conflict and therefore also common methods for resolution of conflict and forging partnerships. Both policing and CSOs have key sectoral responsibilities and reform agendas to implement to ensure that as an individual agency they are able to meet their obligations as partners in the HIV response. Using the key outcomes of discussions and recommendations from these consultations and drawing on existing literature, the objective of this paper is to present a preliminary model that roadmaps the critical path from resolution of conflict to partnership between LEAs and CSOs. Conclusions This paper seeks to highlight that critical resources are required to support ongoing development and harnessing of partnerships between LEAs and CSOs and argues that these resources should not just come from global HIV funding mechanisms but should be part of a more mainstreamed security sector reform agenda that understands the mutual benefits that programming for human rights-based policing reform would have on HIV, development and security. [ABSTRACT FROM AUTHOR]

Stopping rules for clinical trials are primarily intended to control Type I error rates if interim analyses are planned, but less is known about the impact that potential stopping has on estimating treatment benefit. In this paper, we derive analytic expressions for (1) the over-estimation of benefit in studies that stop early, (2) the under-estimation of benefit in completed studies, and (3) the overall bias in studies with a stopping rule. We also examine the probability of stopping early and the situation in meta-analyses. Numerical evaluations show that the greatest concern is with over-estimation of benefit in stopped studies, especially if the probability of stopping early is small. The overall bias is usually less than 10% of the true benefit, and under-estimation in completed studies is also typically small. The probability of stopping depends on the true treatment effect and sample size. The magnitude of these effects depends on the particular rule adopted, but we show that the maximum overall bias is the same for all stopping rules. We also show that an essentially unbiased meta-analysis estimate of benefit can be recovered, even if some component studies have stopping rules. We illustrate these methods using data from three clinical trials. The results confirm our earlier empirical work on clinical trials. Investigators may consult our numerical results for guidance on potential mis-estimation and bias in the treatment effect if a stopping rule is adopted. Particular concern is warranted in studies that actually stop early, where interim results may be quite misleading. [ABSTRACT FROM AUTHOR]

Subgroup analyses are an essential part of fully understanding the complete results from confirmatory clinical trials. However, they come with substantial methodological challenges. In case no statistically significant overall treatment effect is found in a clinical trial, this does not necessarily indicate that no patients will benefit from treatment. Subgroup analyses could be conducted to investigate whether a treatment might still be beneficial for particular subgroups of patients. Assessment of the level of evidence associated with such subgroup findings is primordial as it may form the basis for performing a new clinical trial or even drawing the conclusion that a specific patient group could benefit from a new therapy. Previous research addressed the overall type I error and the power associated with a single subgroup finding for continuous outcomes and suitable replication strategies. The current study aims at investigating two scenarios as part of a nonconfirmatory strategy in a trial with dichotomous outcomes: (a) when a covariate of interest is represented by ordered subgroups, eg, in case of biomarkers, and thus, a trend can be studied that may reflect an underlying mechanism, and (b) when multiple covariates, and thus multiple subgroups, are investigated at the same time. Based on simulation studies, this paper assesses the credibility of subgroup findings in overall nonsignificant trials and provides practical recommendations for evaluating the strength of evidence of subgroup findings in these settings. [ABSTRACT FROM AUTHOR]

Advances in high‐throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven‐step "recipe" for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high‐throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients. [ABSTRACT FROM AUTHOR]

Accessible summary: Attention deficit hyperactivity disorder (ADHD) is often missed/underdiagnosed in people with intellectual disability compared to people without intellectual disability.The presence of intellectual disability, autism and challenging behaviour should raise the suspicion of ADHD as comorbid neurodevelopmental disorder.Treatment of ADHD in people with intellectual disability may reduce the need for antipsychotic medications. The diagnosis of ADHD is often missed or misdiagnosed in people with intellectual disability. Despite a significant growth in literature on the diagnosis and treatment of ADHD in people without intellectual disability, there have been few studies on ADHD in people with intellectual disability. In this paper, we describe a group of adults with intellectual disability and ADHD disorder open to a specialist community intellectual disability service. We examined the frequency and dose of antipsychotic use and considered whether ADHD disorder medication is associated with a reduced use of psychotropic medication. The study found a high incidence of autism in people with intellectual disability and ADHD. Men with intellectual disability were given the diagnosis of ADHD more often compared to women with intellectual disability. Only 64% of people with ADHD and intellectual disability taking ADHD medication were on antipsychotic medications compared to 93% of people with ADHD and intellectual disability without ADHD medications. This generates several hypotheses such as whether antipsychotic medications are prescribed to control ADHD symptoms, whether use of ADHD medications can reduce the use of antipsychotic medications and/or whether antipsychotics are used to treat underlying psychiatric comorbidities in people with ADHD. Randomised controlled trials are needed to answer the question whether use of ADHD medication reduces the use of antipsychotic medication in people with intellectual disability and ADHD. Further studies are also needed to explore reason for not using ADHD medication in certain patients with ADHD and intellectual disability and what treatment options are effective in treating psychiatric comorbidities in people with ADHD and intellectual disability. [ABSTRACT FROM AUTHOR]

Accessible summary: Lots of people with autism find it difficult to make friends and have relationships.There are lots of different groups that can help people with autism to learn social skills and how to make friends.Some of the groups were specially designed for people with a learning disability as well as autism.The groups can help support people to talk about their emotions, talk to other people about their thoughts and feelings and practise talking to other people.This paper found that social skills groups can help people with autism to improve their social skills and to talk to people more.The PEERS‐YA group appears to be the best social skills group for people with autism without a learning disability.More research is needed to learn more about social skills groups for people with autism and a learning disability. Background: Social and communication impairments are a core diagnostic feature of autism spectrum disorder (ASD) and can act as a barrier to developing relationships. The National Institute for Health and Care Excellence (2016) guidelines recommend group social skills interventions as the first‐line treatment to help adults with ASD improve their social skills and relationships. To date, reviews have only explored the impact of group social skills interventions for adults with ASD without intellectual disability (ID). This review aimed to critically appraise studies investigating group social skills interventions for adults with ASD both without intellectual disability and with a mild or moderate intellectual disability. Method: A systematic search of four databases (PsycINFO, MEDLINE, EMBASE and CINAHL), as well as hand‐searching of references, was conducted. Ten studies were identified, employing different designs and methodologies, and covering six different group social skills interventions. Results: Overall, the review provided fairly consistent evidence that group social skills in different formats can reduce social impairments and increase social interaction, social knowledge and empathy for adults with ASD. Conclusion: There was variation in the quality of studies, and the most robust evidence was provided for the efficacy of the PEERS‐YA intervention. There was less evidence supporting the effectiveness of group social skills interventions for adults with ASD and intellectual disability, and more research is needed in this area. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor inhibitors (anti‐VEGF) have consistently demonstrated efficacy and safety and changed both the aim and perspectives of diabetic macular edema (DME) treatment. Hence, the present and future role of focal/grid laser photocoagulation in DME treatment has been subjected to some debate. However, extensive insight into technical advances in novel laser systems, treatment protocols of anti‐VEGF trials and the functional impact of modern focal/grid photocoagulation is needed to evaluate the present and future role of photocoagulation in DME treatment. Across a wide range of clinical trials laser therapy was required as adjunctive/rescue treatment in approximately 20–50% of patients receiving anti‐VEGF monotherapy for centre involving DME. Further, a lower retreatment rate and a more stable reduction in retinal thickness have been demonstrated in more studies. However, lacking information on the laser systems used, their technical specifications and protocols of application often complicates direct comparison of results in anti‐VEGF trials. Hence, this paper aimed to provide an overview of the currently available data relevant to the potential role of focal/grid laser photocoagulation in DME treatment including a thorough overview of the current most commonly used laser systems. Results with subthreshold diode micropulse laser photocoagulation are intriguing and may offer a valuable option as adjunctive therapy to anti‐VEGF treatment. However, more well‐designed studies on combination therapy are warranted to determine the full potential of modern retinal photocoagulation systems. In conclusion, current data suggest that focal/grid laser therapy should still be an option for consideration as adjunctive therapy in many patients. [ABSTRACT FROM AUTHOR]

Aim: To assess interobserver reliability in the interpretation of three-dimensional gait analysis (3DGA) of children with gait disorders within a single institution.Method: Seven experienced interpreters in our institution participated in a quality-assurance program reviewing one unique patient's 3DGA data every 3 months. Between 2014 and 2017, 15 patients' data were interpreted (14 with spastic cerebral palsy, 1 with myelodysplasia). Interpreters were asked to select 'yes', 'no', or 'indeterminate' from a list of problems and treatment recommendations. Kappa and percent agreement calculations were performed to evaluate consistency.Results: Average percentage agreement in problem identification and treatment recommendation was greater than 84 percent and 90 percent for all interpreters respectively. Average kappa for the 10 most consistently identified problems and recommended treatments were 0.69 and 0.59 respectively. Interpreter consistency was moderate or better for the most commonly performed operations at our institution (0.44-0.59). Sagittal plane abnormalities of the hip and knee had the highest consistency.Interpretation: When institutional differences in data collection and regional variations in management philosophies are removed, interobserver consistency in 3DGA interpretation is moderate to substantial for many commonly selected items. Identification of areas with poor consistency may help address underlying causes and improve data processes.What This Paper Adds: Consistency in three-dimensional gait analysis interpretation and treatment recommendation is high within a single institution. There is moderate or better consistency for most commonly identified problems and recommended treatments. Sagittal plane problem identification of the hip and knee have the highest consistency. Lower consistency is seen in areas with poor objective measures, such as dystonia and balance. [ABSTRACT FROM AUTHOR]

Oxaliplatin is a third‐generation, platinum‐based derivative used to treat advanced colorectal cancer. Within the patient population on oxaliplatin therapy, a lower incidence of hematological adverse effects and gastrointestinal toxicity is noted, but severe neuropathic pain episodes characterized by increased cold and tactile hypersensitivity are present in ~95% of patients. This drug is also used to induce a rodent model of chemotherapy‐induced peripheral neuropathy (CIPN)‐related neuropathic pain which is widely used in the search for novel therapies for CIPN prevention and treatment. This paper provides a step‐by‐step, detailed description of the prevention and intervention protocols used in our laboratory for the assessment of oxaliplatin‐induced cold allodynia in mice. To establish cold sensitivity in mice, the cold plate test was used. Latencies to pain reaction in response to cold stimulus (2.5°C) for vehicle‐treated non‐neuropathic mice, vehicle‐treated mice injected with oxaliplatin (neuropathic control), and oxaliplatin‐treated mice treated additionally with duloxetine are compared. Duloxetine is a serotonin/noradrenaline reuptake inhibitor which was found to produce significant pain relief in patients with CIPN symptoms. In our present study, duloxetine administered intraperitoneally at the dose of 30 mg/kg served as a model antiallodynic drug which attenuated or partially prevented cold allodynia caused by oxaliplatin. [ABSTRACT FROM AUTHOR]

Introduction: A size increase of the gingiva can be a manifestation of gingival disease. While gingival lesions can affect periodontal tissue, only few reports described the association between peripheral giant‐cell granuloma (PGCG) with dental implants and their clinical management. Their clinical relevance is of a great interest since some lesions may lead to extensive bone resorption, esthetic alterations, or even tooth/implant loss. To the author's best knowledge, no specific guidelines for the treatment of PGCG affecting dental implant in the esthetic zone have been reported. The aim of this paper was to report an extensive PGCG associated with a dental implant in the esthetic area and its surgical management. Case Presentation: A 39‐year‐old suffered from concussive trauma on her anterior maxillary dentition leading to an expanded, purplish soft tissue lesion surrounding the implant provisional crown on right central maxillary incisor. After complete lesion excision, the implant neck was carefully and gently debrided. Histological analysis confirmed the diagnosis of PGCG. The patient was then evaluated weekly for the first 3 weeks then monthly. No episodes of recurrence were identified. After 16 weeks of undisturbed healing, a soft tissue augmentation via tunnel technique was elected as the first treatment option to improve esthetics. Final implant restoration was delivered. Follow up at 22 months from biopsy excluded any recurrence of PGCG with stability of peri‐implant soft tissues. Conclusion: Excisional biopsy, careful removal of irritating factors, monitoring, and connective tissue grafting can esthetically improve a malpositioned implant and showed no recurrence over a period of 22 months. [ABSTRACT FROM AUTHOR]

The article offers an overview of research paper that discussed the women-focused topics including the epidemiology of alcohol use among women, health and behavioral consequences of drinking, prenatal alcohol use and interventions, and enhanced alcohol treatment services. It also mentions the objectives of research to examine the harmful physiological and behavioral effects of alcohol in women.

Background: In October 2014, the US Food and Drug Administration released a draft guidance for the development of drugs for the acute treatment of migraine. This guidance offered the option of replacing the previously required 4 co‐primary endpoints: pain freedom, freedom from nausea, freedom from photophobia, and freedom from phonophobia, all at 2 hours posttreatment, with 2 co‐primary endpoints: pain freedom and freedom from most bothersome symptom (MBS) other than pain, both at 2 hours posttreatment. At the time the new draft guidance was released, no large clinical trials had been undertaken with these 2 co‐primary endpoints, posing a challenge in determining the sample size that might be required to achieve statistical significance. As a number of trials have now been completed, we conducted a review of the observed placebo responses, drug effect sizes, and sample sizes to better inform the design of future trials. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane library for primary publications of phase 3 randomized, placebo‐controlled, double‐blind acute migraine treatment trials that used pain freedom and MBS freedom as primary or planned secondary endpoints. For each endpoint, placebo response rates were determined and used to generate estimates of sample size, assuming differences between placebo and active treatment groups of 10%, 15%, and 20%. Sample size calculations were based on 80% power using a 2‐group continuity corrected chi‐square test with a 5% 2‐sided significance level. Results: We identified abstracts or full‐length papers describing results of 8 clinical trials employing the new co‐primary endpoints. The mean placebo response rate for 2‐hour pain freedom was 16.75% (range 11.8‐21.3%) and treatment effect (difference in response rates between active and placebo groups) ranged from 5.0% to 27.2%. For 2‐hour MBS freedom, the mean placebo response rate was 32.8% (range 25.2‐48.1%), and the range of treatment effect was 8.9% to 25.4%. Based on a placebo response rate of 17% for pain freedom, the sample sizes that would have been required to achieve statistical significance were n = 269, n = 128, and n = 77, for treatment effect sizes of 10%, 15%, and 20%, respectively. For MBS, assuming a placebo response rate of 33%, the corresponding required sample sizes would have been n = 389, n = 181, and n = 105. Conclusions: The observed range of placebo response and treatment effect sizes suggests that use of the newly recommended 2 co‐primary endpoints could reduce the sample sizes required to achieve significance compared with past trials using 4 primary endpoints (in which mean and median group sizes for recent trials were 375 and 362, respectively). However, the initial trials using the newly recommended co‐primary endpoints tended to treat more participants than would have been minimally required. We anticipate that with the growing body of information regarding the use of these new endpoints, samples sizes may be more aligned with treatment efficacy, enabling faster and more cost‐effective trials for acute migraine treatment. [ABSTRACT FROM AUTHOR]