Effectiveness Of Available Treatments Research Articles

Macrophages: plastic participants in the diagnosis and treatment of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) rank among the most prevalent types of head and neck cancer globally. Unfortunately, a significant number of patients receive their diagnoses at advanced stages, limiting the effectiveness of available treatments. The tumor microenvironment (TME) is a pivotal player in HNSCC development, with macrophages holding a central role. Macrophages demonstrate diverse functions within the TME, both inhibiting and facilitating cancer progression. M1 macrophages are characterized by their phagocytic and immune activities, while M2 macrophages tend to promote inflammation and immunosuppression. Striking a balance between these different polarization states is essential for maintaining overall health, yet in the context of tumors, M2 macrophages typically prevail. Recent efforts have been directed at controlling the polarization states of macrophages, paving the way for novel approaches to cancer treatment. Various drugs and immunotherapies, including innovative treatments based on macrophages like engineering macrophages and CAR-M cell therapy, have been developed. This article provides an overview of the roles played by macrophages in HNSCC, explores potential therapeutic targets and strategies, and presents fresh perspectives on the future of HNSCC treatment.

Burden of Disease and Treatment Patterns Amongst Patients With Vitiligo: Findings From a National, Longitudinal Retrospective Study in the United Kingdom.

This retrospective study, using UK Clinical Practice Research Datalink and Hospital Episode Statistics databases, analysed 17,239 incident patients with vitiligo. Mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years (range: 0.10 [2010-COVID] to 0.19 [2013/2018]); prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%), and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time were most commonly depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%), and sleep disturbance (12.7%); recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5%, and 3.9%, respectively. Mental health comorbidities were more common among White patients (eg, depression and/or anxiety, 29.0%) than Black (18.8%), Asian (16.1%), and other ethnicities (21.4%). In adolescents, depression and/or anxiety was most commonly diagnosed after vitiligo diagnosis (7.4% vs before, 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 person-years) and general practitioner consultations (97.9/100 person-years). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatments (ie, topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids, phototherapy), increasing to 82.0% the next year; median (95% CI) time from diagnosis to first treatment was 34.0 (31.6-36.4) months. Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments; 16.6% had a record of antidepressant and/or anxiolytic treatments. Most patients were not on vitiligo-related treatments within a year of diagnosis, with time to first treatment >2 years, suggesting that vitiligo may be dismissed as unimportant and not treated early, in part due to limited effectiveness of available treatments. New effective treatments, early initiation, and psychological intervention and support are needed to reduce vitiligo burden on patients.

Comprehensive systematic review and pooled analysis of real-world studies evaluating immunomodulator and biologic therapies for chronic pouchitis treatment.

Pouchitis is a common complication after restorative ileal pouch-anal anastomosis following proctocolectomy for ulcerative colitis. Antibiotic-dependent or antibiotic-refractory chronic pouchitis (CP), which is a common cause of pouch failure affecting 15-20% of patients, is challenging to treat. The efficacy of second-line immunomodulator and biologic therapy remains poorly defined. We present a pooled analysis of real-world efficacy data from peer-reviewed full-text manuscripts, focusing on immunomodulator and biologic therapies in CP. Embase and PubMed databases were searched for full-text articles describing the treatment of CP. We performed a systematic review and pooled analysis of published studies to assess the efficacy of immunomodulators, including thiopurines and methotrexate, and biologics including antitumor necrosis factor, anti-integrin, and interleukin-12/23 antagonists. Clinical and endoscopic response and remission rates were combined for pooled analyses. Rates of treatment discontinuation and safety were also assessed. Pooled analysis comprised 20 full-text articles (485 patients). Overall clinical response rate was 46% (95% CI: 35-59%) and clinical remission rate was 35% (95% CI: 21-52%). Overall endoscopic response and remission rates were 41% (95% CI: 18-68%) and 15% (95% CI: 5-39%), respectively. Individual agents' safety profile was reassuring, with vedolizumab being the most favorable. The real-world efficacy data of immunomodulators in the treatment of CP is insufficient. Vedolizumab and ustekinumab appeared effective and safe for CP, whereas anti-TNFs showed higher rates of adverse events. The high heterogeneity within the studies is attributed to the real-world study design, obfuscating drug efficacy comparisons across the studies. Further studies are required to define the comparative effectiveness of available treatments of CP.

Obesity and menopause.

The global obesity pandemic continues to rise, with figures from the World Health Organization showing that 13% of the world's adult population was obese in 2016. Obesity has significant implications, with an increased risk of cardiovascular diseases, diabetes mellitus, metabolic syndrome, and several malignancies. The menopausal transition is associated with increased obesity, a transition from a gynecoid to an android body shape, and increased abdominal and visceral fat, which further worsens the associated cardiometabolic risks. Whether this increased obesity is a consequence of menopause, age, genetics, or environmental factors has long been debated. Increasing life expectancy means women spend a significant part of their lives in the menopause. As such, understanding this complex interplay of obesity and menopause is important to providing the right advice/management. We review the current evidence on obesity and menopause, focusing on the implications of increased obesity during menopause, the impact of menopause on obesity, and the effect of available treatments on associated morbidities.

Engineered rare-earth nanomaterials for fluorescence imaging and therapy.

Early diagnosis and treatment are of great significance for hindering the progression of brain disease. The limited effects of available treatments and poor prognosis are currently the most pressing problems faced by clinicians and their patients. Therefore, developing new diagnosis and treatment programs for brain diseases is urgently needed. Near-infrared (NIR)-light-responsive, lanthanide-doped upconversion nanoparticles (UCNPs) provide great advantages both in diagnosis and therapy. Hence, we synthesised nanoparticles comprised of a UCNPs core with surface functionalization. UCNPs@Au was used for NIR fluorescence imaging in the brain and inhibiting the growth of mouse glioma 261 (GL261) cells depending on photothermal properties. In addition, a UCNPs core and a mesoporous silica layer as the outer shell with a tannic acid-Al3+ ions (TA-Al) complex as a "gatekeeper" were used for pH-triggered doxorubicin/small interfering ribonucleic acid delivery in vitro. Based on our preliminary results, we expect to develop more multifunctional nanoscale diagnostic and therapeutic agents based on UCNPs for the diagnosis and treatment of brain diseases, including Alzheimer's disease, Parkinson's disease, and brain tumours.

Melatonin as a Potential Approach to Anxiety Treatment.

Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin's benefit in anxiety may reside in its sympatholytic action, interaction with the renin-angiotensin and glucocorticoid systems, modulation of interneuronal signaling and its extraordinary antioxidant and radical scavenging nature. Of importance, the concentration of this indolamine is significantly higher in cerebrospinal fluid than in the blood. Thus, ensuring sufficient melatonin production by reducing light pollution, which suppresses melatonin levels, may represent an endogenous neuroprotective and anxiolytic treatment. Since melatonin is freely available, economically undemanding and has limited side effects, it may be considered an additional or alternative treatment for various conditions associated with anxiety.

The Japan Registry for Adult Subjects of Spinal Muscular Atrophy (jREACT-SMA): Protocol for a Longitudinal Observational Study

Spinal muscular atrophy (SMA) is an autosomal recessive genetic neuromuscular disorder with progressive muscle weakness and atrophy, mainly caused by lower motor neuron degeneration resulting from decreased levels of the survival motor neuron protein. Recently, 3 disease-modifying therapies for SMA (nusinersen, onasemnogene abeparvovec, and risdiplam) were approved in Japan that are expected to improve the prognosis of patients with SMA. Long-term clinical follow-up of adult patients treated with disease-modifying therapies and the natural history of SMA are essential to assess the real-world effectiveness of available treatments. Until recently, nusinersen was the only treatment option for patients with SMA in Japan; however, because Japanese approval of nusinersen was based on global clinical trials in infants and children aged 0-15 years with SMA, the effectiveness of nusinersen in adult patients has not been fully assessed in Japan. In addition, longitudinal clinical data of adult patients have not been systematically collected in Japan. This longitudinal observational study of adult patients with SMA who have been diagnosed with 5q-SMA in Japan aims to gain a better understanding of the natural history of SMA, as well as the long-term effectiveness of disease-modifying therapies. Here, we describe the protocol for the study. The Japan Registry for Adult Subjects of Spinal Muscular Atrophy (jREACT-SMA) study is a longitudinal (prospective and retrospective) observational study with a 60-month prospective follow-up being conducted at 19 investigational sites using the newly established jREACT-SMA registry. Patients aged ≥18 years with genetically confirmed 5q-SMA were planned to be enrolled in the registry from December 2020 to May 2022. The planned enrollment was 100 patients. The protocol was approved on September 28, 2020 (approval 2020-0289) by the ethical review committee of Nagoya University. Registration, demographics, genetic diagnosis, motor functions, patient-reported outcomes/quality-of-life outcomes, and other clinical data have been or will be collected. As of May 2022, 113 patients had been enrolled, and the completion of patient registration has been extended from May 2022 to December 2022. Data at registration and during the follow-up period were and will be prospectively collected at least once a year until November 2025 (maximum 60 months). Data analyses will be conducted when all data have been collected. Results are expected to be available in 2026 and the study is expected to be completed by March 2027. This jREACT-SMA study will provide longitudinal prospective follow-up data in adult patients with SMA in Japan, including data on the natural history of the disease and data on the long-term effectiveness of disease-modifying therapies. University Hospital Medical Information Network Center Clinical Trials Registry UMIN000042015; https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000042015. DERR1-10.2196/38878.

Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation, fibroblast-like synoviocytes (FLS) activation and joint destruction. Fasciola hepatica is a platyhelminth that releases excretory-secretory immunomodulatory products capable of suppressing the Th1 immune response. Despite the effectiveness of available treatments for inducing disease remission, current options are not successful in all patients and may cause side effects. Thus, we evaluated the therapeutic potential of F. hepatica extract on FLS from RA patients and arthritis models.MethodsFLS were isolated from synovial fluid of RA patients, cultured, and exposed to F. hepatica extract (60, 80, and 100 µg/ml) for different time points to assess cell viability, adherence, migration and invasion. For in vivo experiments, mice with antigen (AIA) and collagen (CIA) induced arthritis received a 200 µg/dose of F. hepatica extract daily. Statistical analysis was performed by ANOVA and Student's t-test using GraphPad Prism 6.0.ResultsIn vitro assays showed that extract decreased FLS cell viability at concentration of 100 µg/ml (83.8% ± 5.0 extract vs. 100.0% ± 0.0 control; p < 0.05), adherence in 20% (92.0 cells ± 5.8 extract vs. 116.3 cells ± 7.9 control; p < 0.05), migratory potential (69.5% ± 17.6 extract vs. 100.0% control; p < 0.05), and cell invasiveness potential through the matrigel (76.0% ± 8.4 extract vs. 100.0% control; p < 0.01). The extract reduced leukocyte migration by 56% (40 × 104 leukocytes/knee ± 19.00) compared to control (90.90 × 104 leukocytes/knee ± 12.90) (p < 0.01) and nociception (6.37 g ± 0.99 extract vs. 3.81 g ± 1.44 control; p < 0.001) in AIA and delayed clinical onset of CIA (11.75 ± 2.96 extract vs. 14.00 ± 2.56 control; p = 0.126).ConclusionOur results point out a potential immunomodulatory effect of F. hepatica extract in RA models. Therefore, the characterization of promising new immunomodulatory molecules should be pursued, as they can promote the development of new therapies.Trial registration Collection of synovial liquid and in vitro procedures were approved by the Ethics Committee with Certificate of Presentation of Ethical Appreciation in Plataforma Brasil (CAAE: 89044918.8.0000.5327; date of registration: 26/07/2018).

PO186 / #872 SHORT TERM REDUCTION OF CHRONIC NEUROPATHIC PAIN AFTER HIGH-FREQUENCY REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS): E-POSTER VIEWING

Chronic neuropathic pain (CNP) is a debilitating condition that may affect up to 70% of the population, and severely impacts their quality of life. The effects of available treatments are very limited and most available options are considered ineffective with multiple side effects. There is a critical need to develop a new generation of therapies. Transcranial magnetic stimulation (TMS) is a non-invasive and painless brain stimulation technique that allows us to change brain excitability based on Faraday’s Law of Electromagnetic induction.

HTA48 Minimum Follow-up Time Required for the Detection of the Impact of Treatments on Neuropathic Pain and Gastrointestinal Complaints in Fabry Disease

Fabry disease (FD) is a metabolic disorder with clinical onset during childhood or adolescence. A high percentage of patients with FD suffer from neuropathic pain and gastrointestinal (GI) complaints. The positive effect of available treatments (enzyme replacement therapy with agalsidase alfa/beta (ERT) and migalastat) on these symptoms can improve patients’ quality of life. We investigated the minimum time of follow-up in FD to detect the statistically significant impact on neuropathic pain and GI complaints after treatment with available therapies.

An Easy-to-Implement Risk Score for Targeted Hepatitis C Virus Testing in the General Population.

ABSTRACTDespite the effectiveness of available treatments, hepatitis C virus (HCV) remains a major public health problem, mainly due to the high percentage of undiagnosed individuals. We aim to create an easy-to-implement risk score to facilitate targeted HCV testing in the general population. This is a substudy derived from a prospective study in primary care in Madrid (Spain). Participants completed a 21-question risk assessment questionnaire, followed by HCV testing for those with at least one positive response and those >50 years of age, even if they did not answer positively. We used the population >50 years of age to fit a logistic regression model to create a score predicting the risk of a positive test result. We then performed a sensitivity analysis by applying the score obtained to the population <50 years of age, to assess its diagnostic accuracy. Data collected from 2,302 participants were included in the analysis. The prevalence of HCV infection was 1.3%. Five items were selected, showing a C-statistic of 0.896, i.e., male sex, Eastern European origin, use of intravenous drugs, self-perceived risk of acquired HCV infection, and past hepatitis or unexplained liver disease. The sensitivity was 98%, and the negative likelihood ratio was 0.05 for participants with scores of 0 (49.8% in our sample), ruling out HCV infection with high probability. We obtained similar estimates in the population <50 years of age. This tool achieved high diagnostic accuracy to target HCV testing. This could help optimize resources when universal screening is not feasible.IMPORTANCE Despite the highly effective treatments currently available, HCV remains one of the major public health problems related to an infectious agent, mainly because a high percentage of individuals remain undiagnosed. Universal screening has been proposed as a way to end this epidemic; however, it is not feasible in all settings due to different implementation barriers. With this work, we aim to collaborate in improving the diagnosis of HCV infection by creating a simple 5-item score that rules out HCV infection with a very high probability. Almost one-half of the participants in our sample did not present any affirmative answers to these questions, and their probability of being infected was close to 0%. This tool could be a useful strategy and could be considered a cost-effective alternative to optimize resources when universal screening is not feasible.

Contemporary aspects in pharmacological management of migraine

Migraine is a complex neurological pathology that has a major negative impact on people’s health and quality of life. At the same time, it is a global health problem, for which a definitive therapeutic management has not yet been established. This uncertainty is explained by the multilateral aspect of the pathophysiology of migraine, the individual nature of the clinical manifestations presented by patients, as well as the diversity of the level of effectiveness of available treatments. Therefore, the identification of optimal anti-migraine treatment options should be based on the following principles: understanding and capitalizing on the multifactorial pathogenetic specificity of migraine and the individualized approach to patients. Thus, this combination, together with a productive dialogue between the doctor, the patient and his family, will generate positive results in the treatment of migraine.

Effectiveness of Available Treatments for Gaming Disorders in Children and Adolescents: A Systematic Review.

In 2020, the prevalence of gaming disorder (GD) was comparable with the prevalence of obsessive-compulsive disorder, thus demonstrating the necessity of addressing Internet gaming disorder (IGD) and GD in general. GD has been introduced as a psychiatric disorder by International Classification of Diseases and paving the way for treatment and prevention interventions. In this review, we researched available treatment interventions in children and adolescents. Τhe initial search resulted in 972 studies and we ended up with 16 by excluding inappropriate studies according to six inclusion criteria. The studies confirmed that cognitive-behavioral therapy (CBT) or CBT-based interventions are the most used, and in cases of comorbidity, such as depression or attention-deficit/hyperactivity disorder, the appropriate pharmaceutical intervention also was an effective option. Other interventions combined CBT with family therapy or CBT-based therapies that took place in specialized camps. Family as a supportive expedient or even treatment expedient seemed to play a major role. It is remarkable that only little knowledge exists regarding treatment interventions for children aged 8-12 years old. Therefore, more studies need to be carried out for this age range especially, with comparable efficacy to this of other interventions.

Effect of Transcranial Direct Current Stimulation associated with aerobic exercise on the autonomic modulation of hemiparetic individuals due to stroke: a study protocol for a double-blind randomized controlled trial

Background:Individuals after a stroke have an imbalance in the autonomic nervous system, which increases the risk of death or recurrent episodes of stroke. Transcranial Direct Current Stimulation (tDCS) combined with aerobic exercise has shown an effect on the modulation of this system.Objective:The Heart Rate Variability (HRV) and the distance traveled on the exercise bike will be assessed to verify the additional impact of tDCS combined with aerobic exercise on individuals with chronic stroke sequelae.Methods:The 34 adult individuals with diagnoses of chronic stroke will be randomized into two aerobic exercise intervention groups: G1 (with active tDCS) and G2 (with sham tDCS), three times a week, for 12 weeks.Procedures:tDCS will be implemented during the aerobic exercise with the anodal electrode positioned over the lateral dorsal prefrontal left cortex, and the cathodal electrode over the contralateral supraorbital region, with 2mA, for 20 minutes. Assessments will be carried out pre, immediately after the intervention, and on the 12th, 24th, 36th interventions, and 30 days later.The HRV data that are pulse interval (PI), square root of the mean of the squares of the differences between adjacent normal RR intervals (rMSSD), absolute high frequency (HF), absolute low frequency (LF), high and low frequency ratio (LF / HF) will be collected using a cardio frequency meter. The analysis of the distance traveled on the exercise bike before and after interventions will be analyzed in meters.Discussion:The autonomic control via brain networks after a stroke can be altered and can promote an increase in sympathetic tone, and a higher risk of sudden death or relapse of stroke.  It is crucial to demonstrate the effectiveness of available treatments to improve the autonomic function.Trial registration:The study is registered as aBRAZILIAN CLINICAL TEST RECORD(ReBEC): U1111-1222-4588 on the 2018/10/16

Is the gluten-free and casein-free diet efficacious in the treatment of childhood autism spectrum disorder?

Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions, characterized by early-onset difficulties in social communication as well as repetitive and unusually restricted behaviors and interests. The treatment of ASD is based primarily on psychoeducational and behavioral interventions. Since the effectiveness of available treatments for ASD is limited, many families search for alternative therapies, such as the gluten-free and casein-free (GFCF) diet. Despite the popularity of the GFCF diet as a supplementary treatment in children with ASD, several rigorous evaluations have failed to confirm its effectiveness. The majority of the available studies examining the efficacy of the GFCF diet are seriously flawed and allow no firm conclusions. The available evidence regarding the effectiveness of the GFCF diet in the treatment of childhood ASD is very weak and cannot be considered promising. The GFCF diet should be used only if an allergy or intolerance to nutritional gluten or casein has been established. The identification of a hypothetical diet-related ASD phenotype may help in selecting children who could benefit from a GFCF dietary intervention. An important consideration is that potentially ineffective therapies may imply considerable opportunity costs, with other possibly more effective treatment approaches remaining unutilized.

Effect of Transcranial Direct Current Stimulation associated with aerobic exercise on the autonomic modulation of hemiparetic individuals due to stroke: a study protocol for a double-blind randomized controlled trial

Background: Individuals after a stroke have an imbalance in the autonomic nervous system, which increases the risk of death or recurrent episodes of stroke. Transcranial Direct Current Stimulation (tDCS) combined with aerobic exercise has shown an effect on the modulation of this system. Objective: The Heart Rate Variability (HRV) and the distance traveled on the exercise bike will be assessed to verify the additional impact of tDCS combined with aerobic exercise on individuals with chronic stroke sequelae. Methods: The 34 adult individuals with diagnoses of chronic stroke will be randomized into two aerobic exercise intervention groups: G1 (with active tDCS) and G2 (with sham tDCS), three times a week, for 12 weeks. Procedures: tDCS will be implemented during the aerobic exercise with the anodal electrode positioned over the lateral dorsal prefrontal left cortex, and the cathodal electrode over the contralateral supraorbital region, with 2mA, for 20 minutes. Assessments will be carried out pre, immediately after the intervention, and on the 12th, 24th, 36th interventions, and 30 days later. The HRV data that are pulse interval (PI), square root of the mean of the squares of the differences between adjacent normal RR intervals (rMSSD), absolute high frequency (HF), absolute low frequency (LF), high and low frequency ratio (LF / HF) will be collected using a cardio frequency meter. The analysis of the distance traveled on the exercise bike before and after interventions will be analyzed in meters. Discussion: The autonomic control via brain networks after a stroke can be altered and can promote an increase in sympathetic tone, and a higher risk of sudden death or relapse of stroke.  It is crucial to demonstrate the effectiveness of available treatments to improve the autonomic function. Trial registration: The study is registered as a BRAZILIAN CLINICAL TEST RECORD (ReBEC): U1111-1222-4588 on the 2018/10/16

Evaluating Optimal Treatment for Melanoma: A Network Meta-Analysis

It is necessary to determine the optimal treatment for melanoma as the incidence of melanoma is increasing every year. In this study, we conducted a meta-analysis to compare the effectiveness of available treatments for melanoma. The index keywords “melanoma” and “treatment” were used to search the PubMed, Cochrane Library, Web of Science, and Embase databases, and the articles were limited to randomized controlled trials. The search was filtered for articles published until February 2020, and articles were independently extracted by two reviewers. Network meta-analysis (Stata® 14.0 software network package, Stata Corp LLC TX, USA) was used to compare the effectiveness of the mentioned treatments of melanoma. A total of 616 articles were screened of which 6 were selected for meta-analysis, involving 5 treatment measures and 2 047 patients (those who were not followed up on were excluded). The treatment strategies reported for melanoma included tumor necrosis factor (L19-TNFα) and interleukin-2 (L19IL2) in combination with dacarbazine (L19IL2 + DTIC), DTIC, programmed cell death-1 plus cytotoxic T cell antigen-4 (PD-1 + CTLA-4), PD-1, and CTLA-4. Among L19IL2 + DTIC, DTIC, PD-1 + CTLA-4, PD-1, and CTLA-4, CTLA-4 is found to be the best treatment method for melanoma. Our study findings provide a reference for the clinical treatment of melanoma and can clarify the direction for setting up controlled clinical trials.

Comparative efficacy and acceptability of psychological interventions for the treatment of adult outpatients with anorexia nervosa: a systematic review and network meta-analysis

No consistent first-option psychological interventions for adult outpatients with anorexia nervosa emerges from guidelines. We aimed to compare stand-alone psychological interventions for adult outpatients with anorexia nervosa with a specific focus on body-mass index, eating disorder symptoms, and all-cause dropout rate. In this systematic review and network meta-analysis, we assessed randomised controlled trials about stand-alone pharmacological or non-pharmacological treatments of adult outpatients with anorexia nervosa, defined according to standardised criteria, with data for at least two timepoints relating to either body-mass index or global eating disorder psychopathology. We searched Cochrane CENTRAL, CINAHL, MEDLINE, and PsychINFO for published and unpublished literature from inception until March 20, 2020. The primary outcomes were the change in body mass index and clinical symptoms, and the secondary outcome was all-cause dropout rate, which were all assessed for treatment as usual, cognitive behavioural therapy (CBT), Maudsley anorexia treatment for adults, family-based treatment, psychodynamic-oriented psychotherapies, a form of CBT targeting compulsive exercise, and cognitive remediation therapy followed by CBT. Global and local inconsistencies for the network meta-analysis were measured, and CINeMA was used to assess the confidence in evidence for primary outcomes. The protocol is registered in PROSPERO (CRD42017064429). Of 14 003 studies assessed for their title and abstract, 16 (0·1%) randomised controlled trials for psychological treatments were included in the systematic review, of which 13 (0·1%) contributed to the network meta-analysis, with 1047 patients in total (of whom 1020 [97·4%] were female). None of the interventions outperformed treatment as usual in our primary outcomes, but the all-cause dropout rate was lower for CBT than for psychodynamic-oriented psychotherapies (OR 0·54, 95% CI 0·31-0·93). Heterogeneity or inconsistency emerged only for a few comparisons. Confidence in the evidence was low to very low. Compared with treatment as usual, specific psychological treatments for adult outpatients with anorexia nervosa can be associated with modest improvements in terms of clinical course and quality of life, but no reliable evidence supports clear superiority or inferiority of the specific treatments that are recommended by clinical guidelines internationally. Our analysis is based on the best data from existing clinical studies, but these findings should not be seen as definitive or universally applicable. There is an urgent need to fund new research to develop and improve therapies for adults with anorexia nervosa. Meanwhile, to better understand the effects of available treatments, participant-level data should be made freely accessible to researchers to eventually identify whether specific subgroups of patients are more likely to respond to specific treatments. Flinders University, National Institute for Health Research Oxford Health Biomedical Research Centre.

Diazepam’s antifungal activity in fluconazole-resistant Candida spp. and biofilm inhibition in C. albicans: evaluation of the relationship with the proteins ALS3 and SAP5

The genus Candida spp. has been highlighted as one of the main etiological agents causing fungal infections, with Candida albicans being the most prominent, responsible for most cases of candidemia. Due to its capacity for invasion and tissue adhesion, it is associated with the formation of biofilms, mainly in the environment and hospital devices, decreasing the effectiveness of available treatments. The repositioning of drugs, which is characterized by the use of drugs already on the market for other purposes, together with molecular-docking methods can be used aiming at the faster development of new antifungals to combat micro-organisms. This study aimed to evaluate the antifungal effect of diazepam on mature C. albicans biofilms in vitro and its action on biofilm in formation, as well as its mechanism of action and interaction with structures related to the adhesion of C. albicans, ALS3 and SAP5. To determine the MIC, the broth microdilution test was used according to protocol M27-A3 (CLSI, 2008). In vitro biofilm formation tests were performed using 96-well plates, followed by molecular-docking protocols to analyse the binding agent interaction with ALS3 and SAP5 targets. The results indicate that diazepam has antimicrobial activity against planktonic cells of Candida spp. and C. albicans biofilms, interacting with important virulence factors related to biofilm formation (ALS3 and SAP5). In addition, treatment with diazepam triggered a series of events in C. albicans cells, such as loss of membrane integrity, mitochondrial depolarization and increased production of EROs, causing DNA damage and consequent cell apoptosis.

Trajectory of Serum Bilirubin Predicts Spontaneous Recovery in a Real-World Cohort of Patients With Alcoholic Hepatitis

Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments. We analysed the trajectory of serum bilirubin concentration over the course of hospital admissions in patients with AH to predict spontaneous survival and the need for treatment. data from 426 patients were analysed. Based on bilirubin trajectory, patients were categorized into three groups: 'fast fallers' (bilirubin <0.8 x admission value at day 7), 'static' (bilirubin of >0.9 - <1.2 x admission value) and 'rapid risers' (bilirubin of ≥1.2 x admission bilirubin). Fast fallers had significantly better 90-day survival compared to other groups (log rank p < .001), and showed no benefit of corticosteroid therapy (OR for survival at 28 days of treatment, 0.94, 95% CI 0.06 - 8.41). These findings remained even amongst patients with severe disease based on initial DF, GAHS or MELD scores. We present an intuitive method of classifying patients with AH based on the trajectory of bilirubin over the first week of admission. It is complimentary to existing scores that identify candidates for corticosteroid treatment or assess response to treatment. This method identifies a group of patients with AH who recover spontaneously and can avoid corticosteroid therapy.