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Background Methods Results Conclusion An innovative New South Wales government funded statewide Cannabis Medicines Advisory Service (CMAS) operated between January 2018 and June 2022. The service provided comprehensive patient‐specific and evidence‐based information to support health professionals in prescribing and patient care decisions. This study aimed to describe real‐world data collected by CMAS.A sub‐set of de‐identified, patient‐specific enquiries collected between January 2021 and June 2022 (n = 123/567; 21.7%) were analyzed using R version 4.2.1. Diagnosis, indication, and comorbidities were coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology.Most patient‐specific enquiries from medical practitioners were from general practitioners (n = 103/123; 83.7%). Female (n = 53/123; 43.1%) and male (n = 59/123; 48.0%) patients were similarly represented. Sex was not specified for 8.9% (n = 11/123) of patients. The mean age of patients was 52.1 years (range <10–90). The most common three diagnoses were osteoarthritis, anxiety, and chronic pain. Indications that were most frequently reported included chronic pain, anxiety, back pain, non‐neuropathic pain, and insomnia. Comedications were most commonly non‐opioid and opioid analgesics and antidepressants. Most practitioners were considering prescribing a cannabidiol (CBD) product for their patient. Cannabinoid composition selection guidance provided by CMAS was predominantly (delta‐9‐tetrahydrocannabinol) THC:CBD ~1:1, followed by CBD‐only products. CMAS was contacted by health professionals regarding the management of potential adverse events for five patients.The findings of this study shed light on the information medical practitioners were seeking to inform their clinical decision‐making about medical cannabis and can inform the development of clinical guidance resources. [ABSTRACT FROM AUTHOR]

Objective Head-neck paragangliomas (HNPGLs) are rare tumors with approximately half arising due to germline pathogenic variants (PVs) in succinate dehydrogenase genes (SDHx). Patients with HNPGL have heterogeneous propensity to recur and metastasize. Thus, we aim to assess prevalence and predictors of recurrent (RD) and/or metastatic disease in patients with and without SDHx -related HNPGLs. Design and methods This cross-sectional study used retrospective data of 214 patients enrolled in six referral centers. Data included sex, age, primary tumor treatment, location, and size, biochemical phenotype, germline PVs, presence of RD (locoregional or new tumor), and/or metastasis. Results Patients with and without SDHx -related HNPGLs showed 74% and 40% prevalence of RD, respectively. Patients without SDHx -related HNPGLs presented with recurrent tumors only in head-neck regions. The only independent predictor for RD in the entire cohort was presence of SDHx PVs. Metastatic prevalence reached 9%-13%. For patients with SDHx -related HNPGLs, large tumor size (>2.3 cm, OR:50.0, CI:2.6-977.6), young age at initial diagnosis (<42years, OR:27.3, CI:1.8-407.2), and presence of SDHB PV (OR:15.6; CI:1.5-164.8) were independent predictors of metastasis. For patients without SDHx -related HNPGLs, only carotid-body location was an independent predictor of metastasis (OR:18.9, CI:2.0-182.5). Conclusions Patients without SDH x-related HNPGLs require long-term follow-up due to high prevalence of RD with imaging largely restricted to head-neck regions. As carotid-body HNPGLs have the highest metastatic risk among sporadic tumors, radical treatment with frequent follow-up is suggested until population-based data are available. Importantly, patients with SDHx -related HNPGLs might benefit from early radical treatment when tumors are still small to reduce metastatic risk. [ABSTRACT FROM AUTHOR]

Frameworks of care have been developed to enhance and standardise care for those with venous leg ulcers. Community nurses are faced with an array of frameworks and guidance documents on which to base their care. This article outlines and discusses variations in the information provided within the body of evidence relating to the care of venous leg ulcers. It is based on the findings of ongoing study for a PhD thesis. [ABSTRACT FROM AUTHOR]

Children's exposure to intimate partner violence (CEIPV) between parents and other caregivers accounts for nearly half of all cases investigated and substantiated by child welfare authorities in Canada. The emotional, physical, and behavioural impairments associated with CEIPV are similar to effects of other forms of child maltreatment. The identification of children and youth who have been exposed to intimate partner violence (IPV) can be challenging due to the non-specific behaviours sometimes associated with such exposure, and the stigma and secrecy that often characterize IPV. Also, responding safely to children and youth with suspected CEIPV can be complicated by the need to consider the safety and well-being of a non-offending caregiver. This position statement presents an evidence-informed approach developed by the Violence, Evidence, Guidance, Action (VEGA) Project for the safe recognition and response to children and youth who are suspected of being exposed to IPV. [ABSTRACT FROM AUTHOR]

Background: Recently, observational studies have reported that gastroesophageal reflux disease (GERD) is commonly associated with irritable bowel syndrome (IBS), but the causal relationship is unclear. Methods: We conducted a two-sample Mendelian randomization study using summary data from genome-wide association studies (GWASs) to explore a causal relationship between GERD (N cases = 129,080) and IBS (N cases = 4,605) of European ancestry. Furthermore, the inverse-variance weighted (IVW) method and a series of sensitivity analyses were used to assess the accuracy and confidence of our results. Results: We found a significant association of GERD with IBS (NSNP = 74; OR: 1.375; 95% CI: 1.164-1.624; p < 0.001). Reverse MR analysis showed no evidence of a causal association for IBS with GERD (NSNP = 6; OR: 0.996; 95% CI: 0.960-1.034; p = 0.845). Conclusion: This study provides evidence that the presence of GERD increases the risk of developing IBS, and it is observed from the reverse MR results that IBS did not increase the risk of GERD. [ABSTRACT FROM AUTHOR]

Calcium flux has been successfully verified to play an important role in the malignant proliferation and progression of brain tumors, which can serve as an important diagnosis guide. However, clinical diagnosis based on calcium information remains challenging because of the highly complex and heterogeneous features in calcium signals. Here we propose a calcium feature-based tumor diagnosis and treatment guidance platform (CA-TDT-GP) using random forest analysis framework for the efficient prediction of complex tumor behaviors for clinical therapy guidance. Multiple important features associated with brain tumor biological malignancy were screened out through comprehensive feature importance analysis. It provided useful guidance for understanding the biological process and the selection of drugs of brain tumors. Further clinical validation confirmed the accurate prediction of tumor biological characteristics by the model, with a coefficient of determination of over 0.86 in the same cohort of patients and over 0.77 for the new cohort of patients. We further verified the clinical malignant assessment by this model, which performed a 100% prediction match with diagnosed WHO grades, indicating great potential of the platform for clinical guidance. This promising model provides a new diagnostic and therapeutic tool for brain tumor research and preclinical treatment. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) can have severe impacts on function and quality of life. Up to one third of patients will have an inadequate response to their first line of treatment, with subsequent lines of therapy associated with lower remission rates and higher relapse rates. Recently esketamine has become available for Australian patients, and this agent provides an additional treatment option for those with MDD who have had an inadequate response to two or more antidepressant therapies during the current moderate to severe depressive episode. This paper provides an expert panel's practical recommendations and clinical guidance for establishing esketamine clinics in Australia. Methods: An expert panel (n = 11) comprising psychiatrists, mental health care nurses, pharmacists, and individuals with experience establishing esketamine clinics was convened in Sydney. The panel developed practical recommendations and clinical guidance, which were then further refined. Results: Five key areas were identified: practical considerations for esketamine clinic set‐up, including multidisciplinary care considerations; patient selection; administering esketamine; adverse event management and long‐term follow‐up. Conclusions: Guidance presented in this paper should assist Australian clinicians to set up an esketamine clinic, and provide practical advice on the infrastructure and clinical requirements for treatment of patients with this agent. [ABSTRACT FROM AUTHOR]

Objective: The use of qualitative methods for investigating causation has been controversial ever since the "paradigm wars" of the 1980s. Quantitative and experimental researchers have largely dismissed the relevance of qualitative research for causal investigations, while many qualitative researchers have rejected the concept of causation entirely. However, a growing number of scholars, in both research methods and philosophy, have proposed an alternative perspective, one that sees quantitative and qualitative approaches as having complementary strengths and limitations in understanding causation. In this article, we consider this perspective in relation to the study of causality in psychotherapy research. Method: This paper reviews and integrates key descriptions of the mechanisms for identifying causal processes using qualitative research. Results: An overview of how qualitative methods study causation is presented, considering its implications for both identifying causality and for generalizing causal conclusions. Conclusion: The paper holds relevance for establishing outcomes caused by psychotherapy treatments and for developing clinical practice guidance for the field. [ABSTRACT FROM AUTHOR]

Background: After a traumatic incident in the workplace organisations want to provide support for their employees to prevent PTSD. However, what is safe and effective to offer has not yet been established, despite many organisations offering some form of intervention after a traumatic event. Objective: To systematically review the evidence for post-incident psychosocial interventions offered within one month of a workplace trauma, and to compare the content, effectiveness and acceptability of these interventions. Given the lack of a yet clearly established evidence-base in this field, we sought to examine both published empirical research as well as guidelines published by expert groups working with staff in high-risk roles. Methods: We conducted systematic searches for empirical research across bibliographic databases and searched online for clinical practice guidelines to April 2023. We were also referred to potentially relevant literature by experts in workplace trauma. Both empirical research and clinical guidelines were appraised for their quality. Results: A total of 80 research studies and 11 clinical practice guidelines were included in the review. Interventions included Critical Incident Stress Debriefing (CISD), Critical Incident Stress Management (CISM), unspecified Debriefing, Trauma Risk Management (TRiM), Psychological First Aid (PFA), EMDR, CBT and group counselling. Most research and guidance were of poor quality. The findings of this review do not demonstrate any harm caused by CISD, CISM, PFA, TRiM, EMDR, group counselling or CBT interventions when delivered in a workplace setting. However, they do not conclusively demonstrate benefits of these interventions nor do they establish superiority of any specific intervention. Generic debriefing was associated with some negative outcomes. Current clinical guidelines were inconsistent with the current research evidence base. Nevertheless, interventions were generally valued by workers. Conclusions: Better quality research and guidance is urgently needed, including more detailed exploration of the specific aspects of delivery of post-incident interventions. Organisations often seek to provide some form of psychosocial intervention after a traumatic event in the workplace. Previous reviews have contraindicated particular forms of 'debriefing', however, the evidence for post-incident psychosocial interventions in the workplace has not previously been systematically reviewed. Research evidence was generally of poor quality with limited evidence of effectiveness and clinical guidelines were inconsistent with the evidence. Nevertheless, research did not demonstrate harm from most established interventions and support was valued by workers. [ABSTRACT FROM AUTHOR]

ABSTRACTBackground: After a traumatic incident in the workplace organisations want to provide support for their employees to prevent PTSD. However, what is safe and effective to offer has not yet been established, despite many organisations offering some form of intervention after a traumatic event.Objective: To systematically review the evidence for post-incident psychosocial interventions offered within one month of a workplace trauma, and to compare the content, effectiveness and acceptability of these interventions. Given the lack of a yet clearly established evidence-base in this field, we sought to examine both published empirical research as well as guidelines published by expert groups working with staff in high-risk roles.Methods: We conducted systematic searches for empirical research across bibliographic databases and searched online for clinical practice guidelines to April 2023. We were also referred to potentially relevant literature by experts in workplace trauma. Both empirical research and clinical guidelines were appraised for their quality.Results: A total of 80 research studies and 11 clinical practice guidelines were included in the review. Interventions included Critical Incident Stress Debriefing (CISD), Critical Incident Stress Management (CISM), unspecified Debriefing, Trauma Risk Management (TRiM), Psychological First Aid (PFA), EMDR, CBT and group counselling. Most research and guidance were of poor quality. The findings of this review do not demonstrate any harm caused by CISD, CISM, PFA, TRiM, EMDR, group counselling or CBT interventions when delivered in a workplace setting. However, they do not conclusively demonstrate benefits of these interventions nor do they establish superiority of any specific intervention. Generic debriefing was associated with some negative outcomes. Current clinical guidelines were inconsistent with the current research evidence base. Nevertheless, interventions were generally valued by workers.Conclusions: Better quality research and guidance is urgently needed, including more detailed exploration of the specific aspects of delivery of post-incident interventions.

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy—both pharmacologic intervention and lipoprotein apheresis (LA)—is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide. [ABSTRACT FROM AUTHOR]

BackgroundClinical practice guidelines were continually changing during the COVID-19 pandemic to reflect the best available evidence for a novel virus. In Kazakhstan, the national clinical guidelines for COVID-19 patient care were regularly modified and it was not known if and to what extent these guidelines were being followed in practice.MethodsWe conducted a sub-analysis of data collected from an observational study among people hospitalized with COVID-19 in a large infectious disease hospital in Almaty in four cross-sections of increased COVID-19 incidence: T1 (1 June–30 August 2020); T2 (1 October–31 December 2020); T3 (1 April–31 May 2021); and T4 (1 July–26 October 2021). Modifications to the national COVID-19 treatment guidelines were identified and clinical data were abstracted from electronic medical records. We assessed frequency of antibiotic, glucocorticoid, anticoagulant, and antiviral administered in each period and determined if these aligned with national clinical guidelines. We used multivariable logistic regression to compare practices across periods.ResultsSix modifications were made to national COVID-19 treatment guidelines during this study. Of 1,146 people hospitalized with COVID-19, 14% were in T1, 14% in T2, 22% in T3, and 50% in T4. Anticoagulant treatment was administered to 87% (range: 56%–95%), antibiotic treatment to 60% (range: 58%–64%), glucocorticoid to 55% (range: 43%–64%) and antiviral therapy 15% (range: 7%–22%). Majority of treatments were not aligned with national guidelines, including 98% of anticoagulant use, 95% of antibiotic use, 56% of glucocorticoid use, and 56% of antiviral use. There were no significant changes in practice following changes in guidelines for antibiotic use (64% in T1 to 58% in T2, p = 0.30). There was significant increase in use of anticoagulant (84% in T2 vs. 95% in T3, p

Multisystem inflammatory syndrome in children (MIS‐C) is a rare, but severe complication of coronavirus disease 2019 (COVID‐19). It develops approximately 4 weeks after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS‐C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS‐C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS‐C, diagnosis, treatment, follow‐up, and the role of COVID‐19 vaccinations. MIS‐C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS‐C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS‐C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short‐term outcome, MIS‐C patients should be followed‐up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID‐19 vaccination is a safe and effective measure to prevent MIS‐C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS‐C developed by the Immunology Section of the EAACI. [ABSTRACT FROM AUTHOR]

Plain English summary Arthrogryposis multiplex congenita (AMC) is a group of rare disorders where a child is born with stiff joints. Joint stiffness can be present in different parts of the body, making it difficult for the child to move, to walk and to participate in activities. Rehabilitation interventions starting early in life are very important to maximize autonomy. AMC being rare, it is difficult for clinicians to develop experience with this population and there is little research specific to rehabilitation interventions in AMC. In a previous research project, a group of youth with AMC and their families identified five areas of priority for rehabilitation: muscle and joint function, pain, mobility and self-care, participation and psychosocial wellbeing. The purpose of this project is to provide guidance for the evaluation and treatment of children with AMC, in these priority areas. The project involves multiple steps. First, we will perform an online survey with international rehabilitation practitioners to learn about current evaluation and treatment approaches used with children with AMC. We will then bring together expert clinicians, patient and family representatives, and researchers to develop the guidance statements. Then, we will perform an online survey with a larger group of international experts to validate and finalize the guidance statements. Finally, we will interview rehabilitation clinicians and managers to find out about what could help them or limit them in integrating this guidance into their practice. This project will provide healthcare users and providers with research and expert-based guidance for the rehabilitation of children with AMC.

Wound infection is a major challenge for clinicians globally, with accurate and timely identification of wound infection being critical to achieving clinical and cost-effective management, and promotion of healing. This paper presents an overview of the development of the International Wound Infection Institute (IWII)'s 2022 Wound Infection in Clinical Practice consensus document. The updated document summarises current evidence and provides multidisciplinary healthcare providers with effective guidance and support on terminology, paradigms related to biofilm, identification of wound infection, wound cleansing, debridement and antimicrobial stewardship. Integral to the update is revision of wound infection management strategies which are incorporated within the IWII's Wound Infection Continuum (IWII–WIC) and management plan. The aim of the 2022 IWII consensus document update was to provide an accessible and useful clinical resource in at least six languages, incorporating the latest evidence and current best practice for wound infection and prevention. Dissemination techniques for the consensus are discussed and highlighted. [ABSTRACT FROM AUTHOR]

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis. [ABSTRACT FROM AUTHOR]

In June 2022, the MHRA published advice stating that vitamin B12 deficiency is now considered to be a common side effect in people on metformin treatment, especially those receiving a higher dose or longer treatment duration and in those with existing risk factors. This article is a brief review of metformin-associated B12 deficiency and its implications for practice, including screening, treatment and monitoring. [ABSTRACT FROM AUTHOR]

Background: Arthrogryposis multiplex congenita (AMC) is a group of rare congenital disorders characterized by multiple joint contractures present at birth. Contractures can affect different body areas and impact activities of daily living, mobility and participation. Although early rehabilitation is crucial to promote autonomy and participation in children with AMC, empirical evidence to inform best practice is scarce and clinical expertise hard to develop due to the rarity of AMC. Preliminary research involving stakeholders in AMC (youth with AMC, parents, and clinicians) identified priorities in pediatric rehabilitation. Scoping reviews on these priorities showed a lack of high quality evidence related to rehabilitation in AMC. The objective of this project is to provide rehabilitation expert guidance on the assessment and treatment of children with AMC in the areas of muscle and joint function, pain, mobility and self-care, participation and psychosocial wellbeing. Methods: An integrated knowledge translation approach will be used throughout the project. Current rehabilitation practices in AMC will be identified using a clinician survey. Using the Grading of Recommendations, Assessment, Development and Evaluations framework (GRADE) approach, a panel of interdisciplinary expert clinicians, patient and family representatives, and researchers will develop expert guidance on the assessment and treatment for pediatric AMC rehabilitation based on findings from the scoping reviews and survey results. Consensus on the guidance statements will be sought using a modified Delphi process with a wider panel of international AMC experts, and statements appraised using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Theoretical facilitators and barriers toward implementing clinical guidance into practice will be identified among rehabilitation clinicians and managers to inform the design of dissemination and implementation strategies. Discussion: This multi-phase project will provide healthcare users and providers with research-based, expert guidance for the rehabilitation of children with AMC and will contribute to family-centered practice. Plain English summary: Arthrogryposis multiplex congenita (AMC) is a group of rare disorders where a child is born with stiff joints. Joint stiffness can be present in different parts of the body, making it difficult for the child to move, to walk and to participate in activities. Rehabilitation interventions starting early in life are very important to maximize autonomy. AMC being rare, it is difficult for clinicians to develop experience with this population and there is little research specific to rehabilitation interventions in AMC. In a previous research project, a group of youth with AMC and their families identified five areas of priority for rehabilitation: muscle and joint function, pain, mobility and self-care, participation and psychosocial wellbeing. The purpose of this project is to provide guidance for the evaluation and treatment of children with AMC, in these priority areas. The project involves multiple steps. First, we will perform an online survey with international rehabilitation practitioners to learn about current evaluation and treatment approaches used with children with AMC. We will then bring together expert clinicians, patient and family representatives, and researchers to develop the guidance statements. Then, we will perform an online survey with a larger group of international experts to validate and finalize the guidance statements. Finally, we will interview rehabilitation clinicians and managers to find out about what could help them or limit them in integrating this guidance into their practice. This project will provide healthcare users and providers with research and expert-based guidance for the rehabilitation of children with AMC. [ABSTRACT FROM AUTHOR]

Simon Read,1 James Morgan,2 David Gillespie,3 Claire Nollett,3 Marjorie Weiss,4 Davina Allen,1 Pippa Anderson,5 Heather Waterman1 1School of Healthcare Sciences, Cardiff University, Cardiff, Wales, UK; 2Cardiff and Vale University Health Board, Cardiff, Wales, UK; 3Centre for Trials Research, Cardiff University, Cardiff, Wales, UK; 4School of Pharmaceutical Sciences, Cardiff University, Cardiff, Wales, UK; 5Swansea Centre for Health Economics, Swansea University, Swansea, Wales, UKCorrespondence: Simon ReadCardiff University, Room 12.14, Eastgate House, 35-43 Newport Road, Cardiff CF24 0AB, Wales, UKTel +44 2920 688930Email readsm@cardiff.ac.ukAbstract: Patient adherence to medication is an ongoing concern for clinicians, obfuscating treatment efficacy and resulting in wastage of medicine, reduced clinical benefit, and increased mortality. Despite this, procedural guidance on how clinicians should best engage patients regarding their medicine-taking is limited in the United Kingdom. Adherence for chronic conditions is notably complex, requiring clear education, communication, and behavioural shifts to initiate and sustain daily regimens successfully. This article explores current clinician guidance on assuring patient adherence to medication within the National Health Service, comparing it to that provided for healthcare workers in the field of behavioural change. Outlining the inertia of the former and the progress of the latter, we consider what steps should be taken to address this deficit, including greater focus on patient concerns, as well as knowledge translation for healthcare professionals in future adherence research. Current United Kingdom clinical guidance for assuring patient adherence is largely outdated based on inconclusive evidence for best practice. However, efforts to encourage behavioural change in the public health setting demonstrate evidence-based success. Integrating knowledge generated around adherence behaviour and the practical application of adherence and behavioural change research, as well as funding for longer-term studies with a focus on clinical outcomes, may help to solidify the NICE guidance on adherence and further progress the field. This would require close involvement from patient groups and networks informing ethical aspects of study design and clinical implementation.Keywords: adherence, chronic conditions, behavioural change, clinical guidance, knowledge translation

The co-occurrence of autism and gender diversity has been increasingly studied in the past decade. It is estimated that ∼11% of transgender and gender-diverse (TGD) individuals are diagnosed with autism. However, there is insufficient knowledge about appropriate gender-related clinical care for autistic TGD individuals. We performed a scoping review of current clinical guidance for the care of TGD individuals to identify what was said about autism. Clinical guidance documents were searched in PubMed, Web of Science, Google Scholar, Embase, Guidelines International Network, and TRIP medical database, as well as reference mining and expert recommendation. Evidence was synthesised by narrative synthesis, recommendation mapping, and reference frequency analysis. Out of the identified 31 clinical guidance documents, only eleven specifically mentioned the intersection between autism and TGD. Key concepts among the available recommendations included advocating for a multidisciplinary approach; emphasising the intersectionality of autism and gender-diverse experiences during assessments; and-importantly-recognising that autism, in itself, does not serve as an exclusion criterion for receiving gender-related care. However, detailed and practical clinical guidance is lacking due to a gap in evidence. Empirical research into the care experiences and outcomes of autistic TGD individuals using a developmental, lifespan, and strengths-based approach is needed to generate evidence-informed and tailored guidance., Funding: This study was funded through a Canadian Institutes of Health Research Sex and Gender Science Chair program (GSB 171373) awarded to M-CL., Competing Interests: Dr. Bo has nothing to disclose. Dr. van der Miesen reports grants from Centre for Addiction and Mental Health womenmind post-doctoral fellowship, grants from Arcus Foundation, grants from Robert Wood Johnson Foundation, grants from KNAW Ter Meulen grant, grants from Organisation for Autism Research, personal fees from WPATH GEI, outside the submitted work; and served leadership roles with the European Professional Association for Transgender Health (EPATH) and the Federatie Medisch Specialisten (FMS), The Netherlands. Sascha Klomp reports receiving honorarium for training for providers, policy makers, family members, organizations on the intersection of autism and gender diversity; and served as advisory board members for a study on genetics, gender diversity, and mental health, and a study on autism and gender diversity funded by the Organization for Autism Research. Dr. Williams reports grants from National Institute on Deafness and Other Communication Disorders (NIH), grants from National Institute of General Medical Sciences (NIH), personal fees from F. Hoffman LaRoche, Ltd. (Roche), personal fees and non-financial support from Autism Speaks, personal fees from Autism Intervention Research Network for Physical Health (AIR-P), Autistic and Neurodivergent Researchers Working for Equity in Reserch (ANSWER), during the conduct of the study. Dr. Szatmari has nothing to disclose. Dr. Lai reports grants from Canadian Institutes of Health Research, grants from University of Toronto, grants from Centre for Addiction and Mental Health, outside the submitted work., (© 2024 The Author(s).)

Hereditary thrombophilia is a condition in which individuals are susceptible to the formation of thrombi due to a hereditary deficiency in anticoagulant factors, antithrombin (AT), protein C (PC), or protein S (PS). Many Japanese thrombophilia patients have PS deficiency, especially PS p.K196E (also called as PS Tokushima), which is exclusive to the Japanese population, and thrombosis sometimes occurs during pregnancy. At present, no management guidelines for pregnancy and delivery in thrombophilia patients have been developed. The Study Group for Hereditary Thrombophilia, one of the research groups of blood coagulation abnormalities in the Research Program on Rare and Intractable Diseases supported with the Research Grants of the Ministry of Health, Labour and Welfare Science, has therefore developed this clinical guidance to provide healthcare workers with necessary information on safe pregnancy, parturition and neonatal management, adopting a format of responses to seven clinical questions (CQ). At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated. [ABSTRACT FROM AUTHOR]

The scientific landscape of treatments for type 2 diabetes (T2D) has changed rapidly in the last decade with newer treatments becoming available. However, a large proportion of people with T2D are not able to achieve glycaemic goals because of clinical inertia. The majority of T2D management is in primary care, where clinicians (medical, nursing and pharmacist staff) play an important role in addressing patient needs and achieving treatment goals. However, management of T2D is challenging because of the heterogeneity of T2D and complexity of comorbidity, time constraints, guidance overload and the evolving treatments. Additionally, the current coronavirus disease pandemic poses additional challenges to the management of chronic diseases such as T2D, including routine access to patients for monitoring and communication. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a class of agents that have evolved rapidly in recent years. These agents act in a glucose-dependent manner to promote insulin secretion and inhibit glucagon secretion, as well as enhancing satiety and reducing hunger. As a result, they are effective treatment options for people with T2D, achieving glycated haemoglobin reductions, weight loss and potential cardiovascular benefit, as monotherapy or as add-on to other glucose-lowering therapies. However, given the complexity of managing T2D, it is important to equip primary care clinicians with clear information regarding efficacy, safety and appropriate positioning of GLP-1 RA therapies in clinical practice. This review provides a summary of clinical and real-world evidence along with practical guidance, with the aim of aiding primary care clinicians in the initiation and monitoring of GLP-1 RAs to help ensure that desired outcomes are realised. Furthermore, a benefit/risk tool has been developed on the basis of current available evidence and guidelines to support primary care clinicians in selecting individuals who are most likely to benefit from GLP-1 RA therapies, in addition to indicating clinical situations where caution is needed. [ABSTRACT FROM AUTHOR]

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence‐based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a 'good death'. This new position paper aims to provide day‐to‐day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline‐directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure. [ABSTRACT FROM AUTHOR]

With the availability of second-generation basal insulin analogs, insulin degludec (100 and 200 units/ml [degludec]) and insulin glargine 300 units/ml (glargine U300), clinicians now have long-acting, efficacious treatment options with stable pharmacokinetic profiles and associated low risks of hypoglycemia that may be desirable for many patients with type 2 diabetes. In this narrative review, we summarize the current evidence on glycemic control in hospitalized patients and review the pharmacokinetic properties of degludec and glargine U300 in relation to the challenges these may pose during the hospitalization of patients with type 2 diabetes who are receiving outpatient regimens involving these newer insulins. Their increased use in clinical practice requires that hospital healthcare professionals (HCPs) have appropriate protocols to transfer patients from these second-generation insulins to formulary insulin on admission, and ensure the safe discharge of patients and transition back to degludec or glargine U300. However, there is no guidance available on this. Based on the authors' clinical experience, we identify key issues to consider when arranging hospital care of such patients. We also summarize the limited available evidence on the potential utility of these second-generation basal insulin analogs in the non-critical inpatient setting and identify avenues for future research. To address current knowledge gaps, it is important that HCPs are educated about the differences between standard formulary insulins and second-generation insulins, and the importance of clear communication during patient transitions. [ABSTRACT FROM AUTHOR]

Rationale, aims, and objectives: Despite research being done on spinal tuberculosis, diagnosing this condition at an early stage remains problematic due to its insidious onset and the varying symptoms being associated. Most individuals present to the health care facility with either simple back pain at an early stage or neurological complications at a later stage, when spinal compression and vertebral collapse have occurred as a result of delayed diagnosis. The prevention of secondary complications is therefore dependent on early recognition and diagnosis. The objective of this review was to identify common clinical patterns in case presentations and develop an evidence‐based clinical guidance tool to assist clinicians in the early identification of spinal tuberculosis. Method: A comprehensive literature search was conducted for published spinal tuberculosis case studies, which yielded 28 cases after critical appraisal. Data from the studies were categorized in order to assist with a factor analysis and the development of an evidence framework for screening and diagnosing spinal tuberculosis. An evidence‐based clinical guidance tool was then designed from the data obtained. Results: Factors associated with spinal tuberculosis and frequently reported symptoms and physical signs with which the patient could present upon assessment were identified. Options for investigations at primary, secondary, and tertiary levels were also identified. Conclusion: Through the use of an evidence‐based clinical guidance tool, the clinician could be guided in the early suspicion and management of individuals with spinal tuberculosis and prevention of secondary complications. [ABSTRACT FROM AUTHOR]

Abstract Background Populations exposed to humanitarian emergencies are particularly vulnerable to mental health problems, including new onset, relapse and deterioration of psychotic disorders. Inadequate care for this group may lead to human rights abuses and even premature death. The WHO Mental Health Gap Action Programme Intervention Guide (mhGAP-IG), and its adaptation for humanitarian settings (mhGAP-HIG), provides guidance for management of mental health conditions by non-specialised healthcare professionals. However, the pharmacological treatment of people with non-affective psychosis who do not improve with mhGAP first-line antipsychotic treatments is not addressed. In order to fill this gap, UNHCR has formulated specific guidance on the second-line pharmacological treatment of non-affective psychosis in humanitarian, non-specialised settings. Methods Following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a group of international experts performed an extensive search and retrieval of evidence on the basis of four scoping questions. Available data were critically appraised and summarised. Clinical guidance was produced by integrating this evidence base with context-related feasibility issues, preferences, values and resource-use considerations. Results When first-line treatments recommended by mhGAP (namely haloperidol and chlorpromazine) are not effective, no other first-generation antipsychotics are likely to provide clinically meaningful improvements. Risperidone or olanzapine may represent beneficial second-line options. However, if these second-line medications do not produce clinically significant beneficial effects, there are two possibilities. First, to switch to the alternative (olanzapine to risperidone or vice versa) or, second, to consider clozapine, provided that specialist supervision and regular laboratory monitoring are available in the long term. If clinically relevant depressive, cognitive or negative symptoms occur, the use of a selective serotonin reuptake inhibitor may be considered in addition or as an alternative to standard psychological interventions. Conclusions Adapting scientific evidence into practical guidance for non-specialised health workers in humanitarian settings was challenging due to the paucity of relevant evidence as well as the imprecision and inconsistency of results between studies. Pragmatic outcome evaluation studies from low-resource contexts are urgently needed. Nonetheless, the UNHCR clinical guidance is based on best available evidence and can help to address the compelling issue of undertreated, non-affective psychosis in humanitarian settings.

Background: Recently, observational studies have reported that gastroesophageal reflux disease (GERD) is commonly associated with irritable bowel syndrome (IBS), but the causal relationship is unclear., Methods: We conducted a two-sample Mendelian randomization study using summary data from genome-wide association studies (GWASs) to explore a causal relationship between GERD (N cases = 129,080) and IBS (N cases = 4,605) of European ancestry. Furthermore, the inverse-variance weighted (IVW) method and a series of sensitivity analyses were used to assess the accuracy and confidence of our results., Results: We found a significant association of GERD with IBS (NSNP = 74; OR: 1.375; 95% CI: 1.164-1.624; p < 0.001). Reverse MR analysis showed no evidence of a causal association for IBS with GERD (NSNP = 6; OR: 0.996; 95% CI: 0.960-1.034; p = 0.845)., Conclusion: This study provides evidence that the presence of GERD increases the risk of developing IBS, and it is observed from the reverse MR results that IBS did not increase the risk of GERD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Li, Li and Lun.)

Cardiovascular disease (CVD), including heart failure (HF), is a leading cause of morbidity and mortality in people with type 2 diabetes mellitus (T2DM). CVD and T2DM share common risk factors for development and progression, and there is significant overlap between the conditions in terms of worsening outcomes. In assessing the cardiovascular (CV) safety profiles of anti-diabetic drugs, sodium-glucose co-transporter-2 inhibitor (SGLT2i) therapies have emerged with robust evidence for reducing the risk of adverse CVD outcomes in people with T2DM who have either established CVD or are at risk of developing CVD. A previous consensus document from the Improving Diabetes Steering Committee has examined the potential role of SGLT2is in T2DM management and considered the risk–benefit profile of the class and the appropriate place for these medicines within the T2DM pathway. This paper builds on these findings and presents practical guidance for maximising the pleiotropic benefits of this class of medicines in people with T2DM in terms of reducing adverse CVD outcomes. The Improving Diabetes Steering Committee aims to offer evidence-based practical guidance for the use of SGLT2i therapies in people with T2DM stratified by CVD risk. This is of particular importance currently because some treatment guidelines have not been updated to reflect recent evidence from cardiovascular outcomes trials (CVOTs) and real-world studies that complement the CVOTs. The Improving Diabetes Steering Committee seeks to support healthcare professionals (HCPs) in appropriate treatment selection for people with T2DM who are at risk of developing or have established CVD and examines the role of SGLT2i therapy for these people. Funding: Napp Pharmaceuticals Limited. [ABSTRACT FROM AUTHOR]

Management of hypertension is a cornerstone of diabetes management. In August 2019, NICE published updated guidance on the management of hypertension both in people without diabetes and, specifically, in those with type 2 diabetes. Changes have been made to the advice on diagnosis, starting medications, monitoring, choosing medications and when to refer for same-day specialist review. In this article, the author provides an in-depth review of the NG136 guideline and the changes that have been made. [ABSTRACT FROM AUTHOR]

Abstract Objectives Clinical practice guidelines (CPGs) have been developed to improve standards of healthcare delivery and are associated with better clinical outcomes. In the UK, the National Institute for Health and Care Excellence (NICE) produced guidelines for the treatment of low back pain and sciatica. However, guideline resistant attitudes have been demonstrated by healthcare professionals, including osteopaths. Methods A qualitative study design was chosen, utilising constructivist grounded theory method as a framework to explore osteopaths' perceptions of NICE low back pain and sciatica guidelines in the UK. Seven participants were interviewed, with their interviews transcribed and coded. Results Osteopaths' perceptions of NICE Low Back Pain and Sciatica guidelines are influenced by their conception of uncertainty in the clinical environment, their views of knowledge, approach to clinical decision-making and their professional identity. Conclusions Osteopaths' views of NICE low back pain and sciatica guidelines are varied. Some of these views of LBP guidelines may act as obstacles to their implementation. Pre- and post- osteopathy registration educational strategies should aim to facilitate positive attitudes towards the use of clinical guidance abd the utilisation CPGs in clinical practice. Highlights • Evidence-based guidelines for LBP result in clinically and cost-effective care. • Osteopaths' views of LBP guidelines range from positive to negative and sceptical. • Osteopaths' views of LBP guidelines may act as barriers to their implementation. [ABSTRACT FROM AUTHOR]

Abstract: Management of type 2 diabetes mellitus (T2DM) is complex and challenging, particularly for clinicians working in primary care who are faced with many competing clinical priorities. The range of available T2DM treatments has diversified significantly in recent years, generating a busy and data-rich environment in which evidence is rapidly evolving. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) agents are a relatively new class of oral glucose-lowering therapy that have been available in the UK for approximately 5 years. These agents reduce the reabsorption of glucose in the kidney and increase its excretion via the urine. Conflicting messages and opinions within the clinical community have led to misconceptions concerning the efficacy, safety and appropriate position of SGLT2i therapies within the T2DM treatment pathway. To help address some of these concerns and provide advice regarding the appropriate place of these medicines in clinical practice, the Improving Diabetes Steering Committee was formed. The Committee worked together to develop this review article, providing a summary of relevant data regarding the use of SGLT2i medicines and focusing on specific considerations for appropriate prescribing within the T2DM management pathway. In addition, a benefit/risk tool has been provided (see Fig. 3) that summarises many of the aspects discussed in this review. The tool aims to support clinicians in identifying the people most likely to benefit from SGLT2i treatments, as well as situations where caution may be required.Funding: Napp Pharmaceuticals Limited. [ABSTRACT FROM AUTHOR]

The purpose of the study was to assess the experience of implementing local protocols for the standardization of interventional medical technologies at the regional clinical hospital. There was demonstrated that the implementation of local clinical protocols can reduce the number of misdiagnoses, the total number of clinical and instrumental and clinical-laboratory studies, duration of in-hospital stay. The resynchronization of myocardial contraction by means of biventricular cardiostimulation, regulated by the clinical protocol, allows to achieve significant clinical effect on parameters such as ultimate diastolic pressure in the LV, the area of mitral regurgitation, the functional class on HYHA

Background: Populations exposed to humanitarian emergencies are particularly vulnerable to mental health problems, including new onset, relapse and deterioration of psychotic disorders. Inadequate care for this group may lead to human rights abuses and even premature death. The WHO Mental Health Gap Action Programme Intervention Guide (mhGAP-IG), and its adaptation for humanitarian settings (mhGAP-HIG), provides guidance for management of mental health conditions by non-specialised healthcare professionals. However, the pharmacological treatment of people with non-affective psychosis who do not improve with mhGAP first-line antipsychotic treatments is not addressed. In order to fill this gap, UNHCR has formulated specific guidance on the second-line pharmacological treatment of non-affective psychosis in humanitarian, non-specialised settings.Methods: Following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a group of international experts performed an extensive search and retrieval of evidence on the basis of four scoping questions. Available data were critically appraised and summarised. Clinical guidance was produced by integrating this evidence base with context-related feasibility issues, preferences, values and resource-use considerations.Results: When first-line treatments recommended by mhGAP (namely haloperidol and chlorpromazine) are not effective, no other first-generation antipsychotics are likely to provide clinically meaningful improvements. Risperidone or olanzapine may represent beneficial second-line options. However, if these second-line medications do not produce clinically significant beneficial effects, there are two possibilities. First, to switch to the alternative (olanzapine to risperidone or vice versa) or, second, to consider clozapine, provided that specialist supervision and regular laboratory monitoring are available in the long term. If clinically relevant depressive, cognitive or negative symptoms occur, the use of a selective serotonin reuptake inhibitor may be considered in addition or as an alternative to standard psychological interventions.Conclusions: Adapting scientific evidence into practical guidance for non-specialised health workers in humanitarian settings was challenging due to the paucity of relevant evidence as well as the imprecision and inconsistency of results between studies. Pragmatic outcome evaluation studies from low-resource contexts are urgently needed. Nonetheless, the UNHCR clinical guidance is based on best available evidence and can help to address the compelling issue of undertreated, non-affective psychosis in humanitarian settings. [ABSTRACT FROM AUTHOR]

Background: Statin prescribing should be based on cardiovascular disease (CVD) risk, but evidence suggests overtreatment of low-risk groups and undertreatment of high-risk groups.Aim: To investigate the relationship between CVD risk scoring in primary care and initiation of statins for the primary prevention of CVD, and the effect of changes to the National Institute for Health and Care Excellence (NICE) guidance in 2014.Design and Setting: Historical cohort study using UK electronic primary care records.Method: A cohort was created of statin-naïve patients without CVD between 1 January 2000 and 31 December 2015. CVD risk scores (calculated using QRISK2 available from 2012) and statin initiations were identified. Rates of CVD risk score recording were calculated and relationships between CVD risk category (low-, intermediate-, and high-risk: <10%, 10-19.9%, and ≥20% 10-year CVD risk) and statin initiation were analysed.Results: A total of 1.4 million patients were identified from 248 practices. Of these, 151 788 had a recorded CVD risk score since 2012 (10.67%) and 217 860 were initiated on a statin (15.31%). Among patients initiated on a statin after 2012, 27.1% had a documented QRISK2 score: 2.7% of low-risk, 13.8% of intermediate-risk, and 35.0% of high-risk patients were initiated on statins. Statin initiation rates halved from a peak in 2006. After the 2014 NICE guidelines, statin initiation rates declined in high-risk patients but increased in intermediate-risk patients.Conclusion: Most patients initiated on statins had no QRISK2 score recorded. Most patients at high risk of CVD were not initiated on statins. One in six statin initiations were to low-risk patients indicating significant overtreatment. Initiations of statins in intermediate-risk patients rose after NICE guidelines were updated in 2014. [ABSTRACT FROM AUTHOR]

Background: Lithium is an effective mood stabilizer that is used principally for the management of bipolar disorder (BD). Its administration is complex and often requires sophisticated management and assiduous monitoring. When considering the use of lithium therapy for bipolar disorder, clinicians are advised to refer to recommendations outlined in clinical practice guidelines (CPGs); but because of varying emphases placed by different international CPGs, recommendations addressing the practical use of lithium lack consistency.Method: In order to inform clinicians of optimal lithium therapy for bipolar disorder, we compared and synthesized recommendations for the treatment of bipolar disorder made by recognized CPGs internationally. We conducted a search of the literature and extracted guidance across multiple clinical issues, including clinical indications, disorder subtypes, additional uses, special populations, practical aspects, and side effects.Results: Collectively, CPGs consider lithium most robustly as a first-line intervention for maintenance treatment of bipolar disorder and strongly for the treatment of mania, with relatively modest support for the management of acute bipolar depression. Additionally, there is consensus across the CPGs that lithium tangibly reduces the risk of suicide. Generally, CPGs provide guidance on the many facets of initiating and maintaining patients on lithium therapy, but individually the CPGs varied in terms of depth and practical guidance they provide across these areas. However, consensus was established across many key areas of practice such as the ideal lithium plasma concentration for maintenance and monitoring (0.6-0.8mmol/L), along with the need for regular monitoring of renal and endocrine function. However, with more complex aspects (e.g., atypical presentations) and in special populations (e.g., youth; pregnancy and post-partum; older adults), guidance varied considerably and clear consensus recommendations were more difficult to achieve. In younger adults desirable plasma lithium levels of 0.6-0.8mmol/L can perhaps be achieved with comparatively lower doses and in the very elderly it may be prudent to target lower plasma levels in the first instance. These are important practical points for consideration that, along with many others offered throughout the article, should assist clinicians in dissecting the more complex aspects of management with greater precision.Limitations: This review was limited to CPGs written in English. CPGs are themselves limited by reliance on evidence that often has little resemblance to real-world presentations. An important area that is not sufficiently addressed in the CPGs is clear guidance on the cessation of lithium therapy.Conclusions: Further research is needed on many aspects of lithium therapy and this alongside existing knowledge needs to be used more consistently to inform CPGs, which should also incorporate empirical evidence and clinical experience. The recommendations in this paper provide a useful synthesis of guidance available currently. [ABSTRACT FROM AUTHOR]