Multi-centric evaluation of Truenat MTB and MTB-RIF Dx assays for diagnosis of extrapulmonary tuberculosis.

Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB.

Structural Flexibility and Disassembly Kinetics of Single Ferritin Molecules Using Optical Nanotweezers.

Ferritin, a spherical protein shell assembled from 24 subunits, functions as an efficient iron storage and release system through its channels. Understanding how various chemicals affect the structural behavior of ferritin is crucial for unravelling the origins of iron-related diseases in living organisms including humans. In particular, the influence of chemicals on ferritin's dynamics and iron release is barely explored at the single-protein level. Here, by employing optical nanotweezers using double-nanohole (DNH) structures, we examined the effect of ascorbic acid (reducing reagent) and pH on individual ferritin's conformational dynamics. The dynamics of ferritin increased as the concentration of ascorbic acid approached saturation. At pH 2.0, ferritin exhibited significant structural fluctuations and eventually underwent a stepwise disassembly into fragments. This work demonstrated the disassembly pathway and kinetics of a single ferritin molecule in solution. We identified four critical fragments during its disassembly pathway, which are 22-mer, 12-mer, tetramer, and dimer subunits. Moreover, we present single-molecule evidence of the cooperative disassembly of ferritin. Interrogating ferritin's structural change in response to different chemicals holds importance for understanding their roles in iron metabolism, hence facilitating further development of medical treatments for its associated diseases.

NCCP-ICS joint consensus-based clinical practice guidelines on medical thoracoscopy.

ABSTRACT: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes.

Imagery-Focused Therapy for Visual Hallucinations: A Case Series.

INTRODUCTION: Visual hallucinations (VH) are more common than previously thought and are linked to higher levels of distress and disability in people with a psychotic illness. Despite this, scant attention has been given to VHs in the clinical literature, and the few therapy case series of cognitive behavioural therapy (CBT) published to date have not demonstrated reliable change. In other areas of clinical research, problematic mental imagery has been found to be more strongly related to negative affect in psychological disorders than negative linguistic thinking, and imagery focused techniques have commonly been found to improve the outcomes in CBT trials. Given VHs have many similarities with visual mental imagery and many of the distressing beliefs associated with VHs targeted in CBT are maintained by accompanying mental imagery (i.e., imaging a hallucinated figure attacking them), it seems plausible that an imagery-focused approach to treating VHs may be most effective. METHODS: The current study is a multiple baseline case series (N = 11) of a 10-session imagery-focused therapy for VH in a transdiagnostic sample. RESULTS: The study had good attendance and feedback, no adverse events and only one [seemly unrelated] drop-out, suggesting good feasibility, safety and acceptability. The majority of clients reported reduction on both full-scale measures (administered at 3 baselines, midtherapy, posttherapy and 3-month follow-up) and weekly measures of VH severity and distress, ranging from medium to large effect sizes. CONCLUSIONS: The case series suggests that an imagery-focused approach to treating VHs may be beneficial, with a recommendation for more rigorous clinical trials to follow.

A facile one step route that introduces functionality to polymer powders for laser sintering.

Laser Sintering (LS) is a type of Additive Manufacturing (AM) exploiting laser processing of polymeric particles to produce 3D objects. Because of its ease of processability and thermo-physical properties, polyamide-12 (PA-12) represents ~95% of the polymeric materials used in LS. This constrains the functionality of the items produced, including limited available colours. Moreover, PA-12 objects tend to biofoul in wet environments. Therefore, a key challenge is to develop an inexpensive route to introduce desirable functionality to PA-12. We report a facile, clean, and scalable approach to modification of PA-12, exploiting supercritical carbon dioxide (scCO2) and free radical polymerizations to yield functionalised PA-12 materials. These can be easily printed using commercial apparatus. We demonstrate the potential by creating coloured PA-12 materials and show that the same approach can be utilized to create anti-biofouling objects. Our approach to functionalise materials could open significant new applications for AM.

Emotional and non-emotional mental imagery and auditory verbal hallucinations (hearing voices): A systematic review of imagery assessment tools.

It is unknown to what extent mental imagery and auditory verbal hallucinations (AVHs) are related. Trials evaluating this issue used both emotional and non-emotional mental imagery tools, thereby complicating outcomes comparisons. Therefore, the present study aimed to systematically review the literature on mental imagery in individuals with AVHs to (1) inventory imagery assessment tools used in this population, (2) to collect information on the relation between emotional and non-emotional mental imagery in all sensory domains and AVHs and (3) to integrate the outcomes of this systematic review in a model of different mental imagery domains and related assessment tools. We conducted a systematic literature search in the PubMed Database. After full-text screening, 17 papers were included. Findings showed that a variety of assessment methods have been used to assess various aspects of mental imagery in people with AVHs, suggesting that there is a lack of agreed theoretical conceptualization of mental imagery and AVHs. In addition, the studies confirmed as was expected that non-emotional mental imagery seemed unrelated to AVHs whereas emotional mental imagery was related to AVHs. Lastly, we proposed a model of mental imagery domains and corresponding assessment methods distinguishing between emotional and non-emotional mental imagery.

Clinical performance of single implant prostheses restored using titanium base abutments: A systematic review and meta-analysis.

PURPOSE: The aim of this review was to evaluate the survival rates of restorations utilizing titanium base abutments (TBA) for restoring single-unit implant prostheses. MATERIALS AND METHODS: This review was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The focus question was: In patients who require the restoration of a single dental implant utilizing a titanium base abutment, what are the determining factors and outcomes relating to implant prosthesis prognosis and survival? A comprehensive search of databases (PubMed, EMBASE, and Cochrane Library) was conducted on 16 April 2023 and updated on 5 May 2023. Randomized clinical trials (RCT), retrospective studies and prospective studies, reporting on the use of TBA for single implant prostheses, were reviewed. A Cochrane collaboration risk of bias assessment analysis was performed for randomized clinical studies, and the Newcastle-Ottawa Scale tool was applied for non-randomized studies. A meta-analysis was performed on clinical trials reporting on survival rates of both TBA and other abutments. Other clinical studies, reporting on TBA only, were included for descriptive statistics. RESULTS: The search provided 1159 titles after duplicates were removed. Six RCTs were included to perform a meta-analysis and compare the survival of the TBA to other abutments [OR 0.74; 95% CI: 0.21-2.63, heterogeneity; I2 0%; p = .99]. Twenty-three prospective and retrospective studies fulfilled the criteria and were included in the meta-analysis after 12 months of function. A total of 857 single implant-supported prostheses fabricated with a TBA were included. TBA abutments have an estimate 98.6% survival rate after 1 year in function (95% CI: 97.9%-99.4%). The mean follow-up period was 31.2 ± 16.9 months. CONCLUSIONS: Single implant prosthesis restored with titanium base abutments showed favourable short-term survival rates.

Accelerating the development of a psychological intervention to restore treatment decision-making capacity in patients with schizophrenia-spectrum disorder: a study protocol for a multi-site, assessor-blinded, pilot Umbrella trial (the DEC:IDES trial).

BACKGROUND: A high proportion of patients diagnosed with schizophrenia-spectrum disorders will at some point in their lives be assessed as not having the capacity to make their own decisions about pharmacological treatment or inpatient care ('capacity'). Few will be helped to regain it before these interventions proceed. This is partly because effective and safe methods to do so are lacking. Our aim is to accelerate their development by testing, for the first time in mental healthcare, the feasibility, acceptability and safety of running an 'Umbrella' trial. This involves running, concurrently and under one multi-site infrastructure, multiple assessor-blind randomised controlled trials, each of which is designed to examine the effect on capacity of improving a single psychological mechanism ('mechanism'). Our primary objectives are to demonstrate feasibility of (i) recruitment and (ii) data retention on the MacArthur Competence Assessment Tool-Treatment (MacCAT-T; planned primary outcome for a future trial) at end-of-treatment. We selected three mechanisms to test: 'self-stigma', low self-esteem and the 'jumping to conclusions' bias. Each is highly prevalent in psychosis, responsive to psychological intervention, and hypothesised to contribute to impaired capacity. METHODS: Sixty participants with schizophrenia-spectrum diagnoses, impaired capacity and one or more mechanism(s) will be recruited from outpatient and inpatient mental health services in three UK sites (Lothian, Scotland; Lancashire and Pennine; North West England). Those lacking capacity to consent to research could take part if the key criteria were met, including either proxy consent (Scotland) or favourable Consultee advice (England). They will be allocated to one of three randomised controlled trials, depending on which mechanism(s) they have. They will then be randomised to receive, over an 8-week period and in addition to treatment as usual (TAU), 6 sessions of either a psychological intervention which targets the mechanism, or 6 sessions of assessment of the causes of their incapacity (control condition). Participants are assessed at 0 (baseline), 8 (end-of-treatment) and 24 (follow-up) weeks post-randomisation using measures of capacity (MacCAT-T), mechanism, adverse events, psychotic symptoms, subjective recovery, quality of life, service use, anxiety, core schemata and depression. Two nested qualitative studies will be conducted; one to understand participant and clinician experiences and one to investigate the validity of MacCAT-T appreciation ratings. DISCUSSION: This will be the first Umbrella trial in mental healthcare. It will produce the first 3 single-blind randomised controlled trials of psychological interventions to support treatment decision-making in schizophrenia-spectrum disorder. Demonstrating feasibility will have significant implications not only for those seeking to support capacity in psychosis, but also for those who wish to accelerate the development of psychological interventions for other conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04309435 . Pre-registered on 16 March 2020.

Attachment-focused iMAgery therapy for PSychosis (A-iMAPS): A case series targeting psychosis-related trauma.

OBJECTIVES: The experience of psychosis and its sequelae (including treatment experiences) can be traumatic and affect feelings of safety and security. Until relatively recently, trauma therapy has been avoided with psychosis populations due to concerns about additional harm. Intervention-based research is growing, but focus on psychosis-related trauma is limited. Engendering psychological safety may support engagement with trauma-focused therapy, for which attachment theory provides a strong foundation. Imagery can enhance felt security and is an effective modality for working with trauma. Therefore, this study aimed to examine feasibility and preliminary outcomes of a novel attachment-focused imagery therapy (A-iMAPS) addressing psychosis-related trauma. METHODS: A multiple baseline case series: Participants received between two and five baseline assessments then engaged in the six-session A-iMAPS intervention. Participants completed weekly measures of trauma symptoms and felt security. Further measures were completed pre- and post-intervention. RESULTS: Twelve clinical participants were recruited from NHS services in Northwest England and eight retained through baseline and intervention to the end-of-therapy assessment (attending all sessions). A significant improvement was seen for felt security between baseline and intervention phases. Other measures of trauma symptoms, core schemas, paranoia and attachment varied in change from baseline to end of therapy, but some promising preliminary results were seen. CONCLUSIONS: This study shows that a brief attachment-focused imagery therapy is a promising intervention for targeting psychosis-related trauma, for which there are currently no other specific intervention studies. Utilizing an attachment-informed framework when working with trauma in psychosis should be considered in future intervention studies.

Assessing the delivering of iMAgery-focused therapy for PSychosis (iMAPS) via telehealth.

OBJECTIVES: To examine the feasibility and acceptability of a novel telehealth (video-conferencing software and telephone calls) imagery-based therapeutic intervention for people experiencing persecutory delusions. Utilising a multiple baseline case series design and exploring imagery-focused therapy for psychosis (iMAPS). DESIGN: A non-concurrent A-B multiple baseline design was used. METHODS: Participants experiencing persecutory delusions and self-reporting a psychosis or schizophrenia-spectrum diagnosis were recruited through online adverts. On completion of assessments, participants were randomly assigned to multiple baseline assessments, of between three and five sessions. Six therapy sessions followed, consisting of imagery formulation, safe-place imagery creation, compassionate imagery, imagery manipulation and rescripting. Participants completed pre- and post-measures and sessional measures via an online survey software or in semi-structured interviews. Two weeks post-intervention, a final measure was completed exploring any potential adverse effects of psychotherapy. RESULTS: Five female participants completed all baseline and therapeutic sessions, suggesting the therapy was and mode of delivery was feasible and acceptable. Results indicate strong effect sizes across PANSS positive subscale and mood, as well as participants reporting a clinically significant change in at least one measure, for example, PSYRATS. All participants reported a reduction in the realness and compelling nature of distressing imagery. CONCLUSIONS: Results suggest delivering a telehealth imagery-focused therapy is acceptable and feasibly delivered via telehealth. A control group and blinding of assessments would strengthen the methodological limitations present.

Optical Monitoring of In Situ Iron Loading into Single, Native Ferritin Proteins.

Ferritin is a protein that stores and releases iron to prevent diseases associated with iron dysregulation in plants, animals, and bacteria. The conversion between iron-loaded holo-ferritin and empty apo-ferritin is an important process for iron regulation. To date, studies of ferritin have used either ensemble measurements to quantify the characteristics of a large number of proteins or single-molecule approaches to interrogate labeled or modified proteins. Here we demonstrate the first real-time study of the dynamics of iron ion loading and biomineralization within a single, unlabeled ferritin protein. Using optical nanotweezers, we trapped single apo- and holo-ferritins indefinitely, distinguished one from the other, and monitored their structural dynamics in real time. The study presented here deepens the understanding of the iron uptake mechanism of ferritin proteins, which may lead to new therapeutics for iron-related diseases.

Trauma measures for use with psychosis populations: A systematic review of psychometric properties using COSMIN.

Traumatic events play a key role in the development and course of psychosis. Psychotic symptoms themselves and coercive treatment practices can be inherently traumatic. Hence, reliable and valid methods of assessing trauma and its impact (i.e., Post-Traumatic Stress Disorder (PTSD) symptomology) are essential for use with people with psychosis. Many measures are available to select from, but this is the first review to appraise the psychometric properties of trauma measures to guide decision making regarding instrument use. The review was prospectively registered on Prospero (CRD42022306100). Evaluation of methodological and psychometric quality followed Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidance. Twenty-four articles were eligible, with sixteen trauma measures evaluated. Childhood Trauma Questionnaire- Short Form demonstrated the most robust evidence for assessing experience of trauma. The Trauma and Life Experience (TALE) checklist was the only measure to include specific psychosis and iatrogenic harm items. For PTSD measures, the Symptoms of Trauma Scale and PTSD Symptom Scale- Self Report had the highest quality evidence. Psychometric strengths and weaknesses of various trauma measures are comprehensively evaluated, highlighting future research directions to strengthen the evidence base with emphasis on further evaluation of the TALE, which integrates trauma specific to psychosis.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

Atrial depolarization abnormalities in pulmonary sarcoidosis.

BACKGROUND: Cardiac sarcoidosis, often manifested as sudden death, can be the first manifestation of sarcoidosis. Since 12-lead electrocardiogram (ECG) is recommended as an initial screening tool for cardiac sarcoidosis, the recognition of subtle abnormalities assumes utmost significance. The objective of this study was to identify the electrocardiographic abnormalities in patients with pulmonary sarcoidosis. RESULTS: A detailed analysis of 12-lead ECGs obtained from sixty patients with histopathologically proven pulmonary sarcoidosis and no overt cardiac involvement was done. The findings were compared with those of an age-matched control group. Varying degrees of intraventricular conduction defects were common in the study group [67%], as well as the control group [57%] [P = 0.23]. There was a higher prevalence of biphasic P wave [P = 0.003] and bifid P wave [P = 0.029] in lead III and rsr' in lead aVF [P = 0.03] in the study group as compared to the control group. CONCLUSIONS: Our study demonstrates a greater prevalence of subtle ECG abnormalities in patients with pulmonary sarcoidosis as compared to patients with other forms of pulmonary disease. Atrial depolarization abnormalities were commoner in patients with pulmonary sarcoidosis.

Perspectives of Respiratory Physicians toward Need and Integration of Palliative Care in Advanced Respiratory Diseases.

Objectives: Patients with chronic life-limiting or advanced respiratory diseases often suffer from high symptom burden, requiring palliative care to alleviate symptoms, improve quality of life and restore dignity. The present study explored the perception of respiratory physicians and their current practice of integrating palliative care for adult patients with chronic advanced respiratory diseases. Materials and Methods: An exploratory survey method using Google survey forms and SurveyMonkey was emailed to respiratory physicians between December 2020 and May 2021. Results: One hundred and seventy-two respiratory physicians responded to the survey. The majority of respiratory physicians (n = 153; 88.9%) thought that early integration of palliative care early was beneficial. They did not feel referring to palliative care would result in loss of control on patient care (n = 107; 62.21%) and 66 (38.37%) strongly disagreed that the referral would result in a loss of hope in patients. Further exploration into the training needs of respiratory physicians revealed that 121 (70.35%) felt the need for training in end-of-life care. Conclusion: Respiratory physicians in our study had an inclination toward palliative care integration into their routine clinical practice. A majority of them expressed the need to enhance their skills in palliative care. Therefore, concerted efforts at integration and a mutual exchange of knowledge between respiratory physicians and palliative care physicians will ensure that patients with advanced respiratory diseases are provided high-quality palliative care.

Longitudinal Changes in MRI Muscle Morphometry and Composition in People With Inclusion Body Myositis.

BACKGROUND AND OBJECTIVES: Limited data suggest that quantitative MRI (qMRI) measures have potential to be used as trial outcome measures in sporadic inclusion body myositis (sIBM) and as a noninvasive assessment tool to study sIBM muscle pathologic processes. Our aim was to evaluate changes in muscle structure and composition using a comprehensive multiparameter set of qMRI measures and to assess construct validity and responsiveness of qMRI measures in people with sIBM. METHODS: This was a prospective observational cohort study with assessments at baseline (n = 30) and 1 year (n = 26). qMRI assessments include thigh muscle volume (TMV), inter/intramuscular adipose tissue (IMAT), muscle fat fraction (FF), muscle inflammation (T2 relaxation time), IMAT from T2* relaxation (T2*-IMAT), intermuscular connective tissue from T2* relaxation (T2*-IMCT), and muscle macromolecular structure from the magnetization transfer ratio (MTR). Physical performance assessments include sIBM Physical Functioning Assessment (sIFA), 6-minute walk distance, and quantitative muscle testing of the quadriceps. Correlations were assessed using the Spearman correlation coefficient. Responsiveness was assessed using the standardized response mean (SRM). RESULTS: After 1 year, we observed a reduction in TMV (6.8%, p < 0.001) and muscle T2 (6.7%, p = 0.035), an increase in IMAT (9.7%, p < 0.001), FF (11.2%, p = 0.030), connective tissue (22%, p = 0.995), and T2*-IMAT (24%, p < 0.001), and alteration in muscle macromolecular structure (ΔMTR = -26%, p = 0.002). A decrease in muscle T2 correlated with an increase in T2*-IMAT (r = -0.47, p = 0.008). Deposition of connective tissue and IMAT correlated with deterioration in sIFA (r = 0.38, p = 0.032; r = 0.34, p = 0.048; respectively), whereas a decrease in TMV correlated with a decrease in quantitative muscle testing (r = 0.36, p = 0.035). The most responsive qMRI measures were T2*-IMAT (SRM = 1.50), TMV (SRM = -1.23), IMAT (SRM = 1.20), MTR (SRM = -0.83), and T2 relaxation time (SRM = -0.65). DISCUSSION: Progressive deterioration in muscle quality measured by qMRI is associated with a decline in physical performance. Inflammation may play a role in triggering fat infiltration into muscle. qMRI provides valid and responsive measures that might prove valuable in sIBM experimental trials and assessment of muscle pathologic processes. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that qMRI outcome measures are associated with physical performance measures in patients with sIBM.

Commentary: Bringing together lived experience, clinical and research expertise - a commentary on the May 2022 debate (should CAMH professionals be diagnosing personality disorder in adolescence?).

BACKGROUND: There is a wealth of evidence to suggest that the Borderline Personality Disorder (BPD, or similar Emotionally Unstable Personality Disorder, EUPD) construct is harmful. We provide a commentary on the ideas expressed in the May Debate issue, highlighting both concerns and alternatives. METHOD: We bring together lived experience, clinical and research expertise. This commentary was written collaboratively drawing on all these sources of evidence. RESULTS: We outline evidence that the BPD construct is invalid, harmful, not necessary for effective treatment and a potential block to the development and evaluation of alternatives. CONCLUSIONS: We ask readers to consider these concerns, perspectives and ideas.

Single Dose of Ivermectin is not Useful in Patients with Hematological Disorders and COVID-19 Illness: A Phase II B Open Labelled Randomized Controlled Trial.

Repurposed drugs may reduce morbidity and mortality in patients with hematological disorders who develop COVID-19 illness. 112 patients with predominantly hematological illnesses were randomized to receive standard of care, ivermectin 12 mg [Iv 12] or 24 mg [Iv24] for asymptomatic, mild, or moderate COVID 19 illness. Serial respiratory samples for rRT-PCR samples were sent on Day 3, 5 and 7. rRT-PCR negativity and ≥ 2 log10 reduction in viral loads on day 3, 5 and 7 were similar between the 3 treatment groups across all disease categories. Symptom progression occurred in 26 patients [21.6%] with no difference across 3 treatment groups. Twenty-two patients [18.3%] have expired while 98 [81.7%] survived. Survival rates were similar across treatment groups [controls-80.5%, Iv12-77.5%, Iv24-87.2% respectively]. Overall, poorer survival was seen with moderate illness compared to others [51.6% vs 92.1%; p = 0.000] and was the only significant risk factor identified on multivariate analysis. In this Phase II randomised trial, single dose of 12 or 24 mg of ivermectin did not reduce viral loads, prevent symptom progression, or reduce mortality in patients with predominantly haematological illnesses who develop mild to moderate COVID 19 illness.