Clinical practice guidelines are designed to guide clinical practice and often make causal claims when making recommendations. Sometimes, guidelines make or require stronger causal claims than supplied in the original studies, a phenomenon we call 'causal language jump'. We aimed to evaluate the strength of expressed causation in guidelines and the evidence they reference to assess the pattern of jumps, taking diabetes as an illustrative example. This is a systematic evaluation of guidelines and original studies cited by them, using scoping review design with deviations. Randomly sampled 300 guideline statements (narrative sentences describing evidence to support recommendations) from four selected diabetes guidelines. The eligible guidelines should focus on non-pharmacological treatments or preventive strategies for adult type 2 diabetes mellitus management and related complications. The eligible action recommendations and guideline statements should intend to support non-pharmacological treatments or preventive strategies of type 2 diabetes or in a general diabetic context. We rated the causation strength in the statements and the dependence on causation in recommendations supported by these statements using existing scales. Among the causal statements, the cited original studies were similarly assessed. We then evaluated jumps by checking if the causal claims in guideline statements were stronger than in original studies, and if the causation-dependence in guideline recommendations was stronger than supplied in guideline statements. We also assessed how well they report target trial emulation (TTE) components as a proxy for reliability. Of the 300 statements, 114 (38.0%) were causal, and 76 (66.7%) expressed strong causation. 27.2% (31/114) of causal guideline statements stated stronger causation than any of their references and demonstrated 'causal language jump'; 34.9% (29/83) of guideline recommendations required stronger causation than provided in statements. Of the 53
Multimorbidity, defined as two or more chronic medical conditions, leads to the use of multiple medicines, including for cardiovascular conditions. This is associated with frailty and an increased risk of medication-related harm. Hospitalised adults have higher rates of multimorbidity and frailty compared with non-hospitalised adults. The aim of this study was to examine the use of medicines for hypertension, ischaemic heart disease and atrial fibrillation among patients with multimorbidity and frailty, who are generally not well represented in clinical trials. A cross-sectional study was performed of adults aged ≥45 years with inpatient admissions during an 18-month period. Regular medications prescribed at discharge and coding data were obtained from the electronic medical record and hospital datasets. The prevalence of multimorbidity (using coded chronic medical conditions or the RxRisk pharmaceutical comorbidity index), frailty (using hospital frailty risk score) and polypharmacy (defined as ≥5 medicines) were calculated. The uptake of medicines recommended by the Australian Therapeutic Guidelines for patients with coded hypertension, ischaemic heart disease and atrial fibrillation was also assessed. Two large acute care, teaching hospitals in Adelaide, South Australia. 23 980 unique patients were identified. 69% (n=16 637) of patients had multimorbidity using the coding definition compared with 94% (n=22 620) using the pharmaceutical comorbidity score. 81% (n=19 366) had polypharmacy and 46% (n=11 091) had frailty. More than 85% of patients with hypertension were taking an antihypertensive. More than 75% of patients with ischaemic heart disease were taking an antithrombotic or a lipid-lowering agent and more than 50% were taking an agent acting on the renin-angiotensin system. Over 70% of patients with atrial fibrillation without a contraindication to anticoagulation were taking an anticoagulant. Patients with multimorbidity were 11-51% more likely to be taking an antihypertensive, antithrombotic
This paper aims to describe the development of an inventory of chronic ambulatory care sensitive conditions (ACSCs) relevant to the Malaysian context and identify potentially preventable hospitalisations in the Malaysian Ministry of Health (MOH) facilities based on the developed list. Consultative panel discussion, multi-panel modified Delphi and secondary health data analysis.Setting: Malaysian MOH healthcare facilities. 42 experts from the family medicine and internal medicine specialties (modified Delphi), and 2022 inpatient data from MOH hospitals (secondary health data analysis). A list of chronic ACSCs tailored to the Malaysian context and the proportion of potentially preventable hospitalisation in MOH hospitals. 10 conditions were identified as chronic ACSCs for Malaysia, namely angina, asthma, chronic kidney disease, convulsions and epilepsy, chronic obstructive pulmonary disease, diabetes mellitus, heart failure, hypertension, iron deficiency anaemia and ischaemic heart disease. In 2022, these conditions accounted for 8.6% of potentially preventable hospitalisations among the total hospitalisations in MOH hospitals. This study provides a base list of chronic ACSCs tailored to the Malaysian context, which enables monitoring of potentially preventable hospitalisations due to chronic conditions. The findings underscore a proportion of hospital admissions that could potentially be avoided through interventions that enhance outpatient care. The conditions identified as ambulatory care sensitive provide specific targets for policy action and resource allocation to optimise outpatient health services and thus reduce the burden of hospitalisations in the country. Malaysian National Medical Research Register, NMRR ID-23-02149-TBZ (https://nmrr.gov.my/research-directory/45c901d6-f121-4e79-9f38-dd7d283ec9a6).
Adult-onset Still disease (AOSD) is a systemic autoimmune disorder, and most patients respond well to conventional therapies, including glucocorticoids (GCs), immunosuppressants, and biologic agents. However, a small subset of patients with severe disease remains refractory to treatment and is at risk of developing life-threatening complications.
Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin lymphomas that primarily affects the skin and can mimic inflammatory dermatoses. Unlike many skin diseases, CTCL can lead to disabling symptoms, and advanced CTCL can even be fatal. Early studies investigating health-related quality of life (HRQOL) in patients with mycosis fungoides (MF) and Sézary syndrome (SS), common subtypes of CTCL, demonstrated significant impairment across numerous domains. The aim of this current study is to develop a core domain set (CDS) to identify the essential aspects of MF/SS that influence HRQOL that should be measured in therapeutic clinical trials. In the future, this set of core concepts will be used to identify the best patient- reported outcome measure(s) (PROM) for HRQOL for MF/SS clinical research. Multiple strategies will be used to generate candidate concepts: systematic review of the literature, qualitative study and a survey study of healthcare providers. A Delphi consensus process including a comprehensive group of stakeholders (patients, caregivers/care partners, a multidisciplinary group of healthcare professionals, patient advocacy groups, pharmaceutical industry representatives, methodologists and government agencies) will be used to achieve consensus. Statistical corrections for multiple significance testing and false positive findings will be undertaken. The study was submitted for and received institutional review board approval at the University of Washington (IRB# STUDY00018890 and STUDY00019407). Informed consent will be obtained from all participants where necessary. We will disseminate our findings through peer-reviewed, open access publications and presentations at national/international conferences. We will provide a plain language summary in lay terms for patients and families to patient advocacy groups for distribution to their network. The protocol is registered in the Core Outcome Measures in Effectiveness Trials (COMET) database.
The choroid plexus (CP), one key regulator of cerebrospinal fluid (CSF) production and immune surveillance at the blood-CSF barrier, has recently emerged as a relevant structure in multiple sclerosis (MS) pathophysiology. This review synthesizes current evidence highlighting CP enlargement as measured with magnetic resonance imaging (MRI) as a potential biomarker of neuroinflammation and neurodegeneration in MS. We first outline the basic immunological roles of the CP, emphasizing its function as a dynamic interface facilitating immune cell trafficking and cytokine production within the CNS. Advances in MRI and PET (positron emission tomography) imaging have enabled the quantification of CP volume, revealing enlargement across different MS stages, including radiologically isolated syndrome and pediatric MS. CP volume correlates with lesion load, chronic lesion expansion, microglial activation, and inflammatory CSF profiles, suggesting its responsiveness to neuroinflammatory activity. Notably, CP enlargement is also associated with neurodegenerative processes, including gray matter atrophy, cognitive decline, and disability progression, indicating its potential role also as a surrogate marker of MS-related neurodegeneration. However, methodological variability, confounding factors and a lack of longitudinal standardization challenge the interpretation of CP metrics. We highlight the need for multimodal approaches to unravel the temporal and mechanistic significance of CP enlargement. Future research should also explore CP-targeted interventions and their relevance for MS progression. Overall, CP imaging, in particular its enlargement, offers a novel, biologically meaningful perspective into MS pathogenesis, bridging inflammatory and degenerative pathways, and holds promise for improved disease monitoring.
To present updated evidence-based recommendations with a range of therapeutic options for children in Africa with oligoarticular juvenile idiopathic arthritis (JIA), adopting the treat to-target approach. This study was conducted by the Paediatric Society of the African League Against Rheumatism (PAFLAR) to reach a consensus for recommendations regarding diagnosis and management of oligoarticular JIA suitable for application among different African countries. The Delphi technique was used to reach a consensus of 15 key questions identified by the steering committee. According to the PICO (patient/population, intervention, comparison, outcome) approach, a voting process among 22 African and international clinicians and experts in the field of pediatric rheumatology was performed after intensive systematic review of literature. A consensus was reached for 15 recommendations for diagnosis, monitoring, management of the disease, and its complications, intervention, and when to discontinue treatment of oligoarticular JIA patients with high level of agreement (ranging between 85 and 95%) who agreed or strongly agreed, and the response rate was 100%. These recommendations focus on the early diagnosis and multidisciplinary management of oligoarticular JIA and its complications with high levels of consensus and agreement, improving practice consistency among healthcare providers. Key Points • A panel of experts created a consensus about the early diagnosis of oligoarticular JIA • Consensus-based recommendations to the management of oligoarticular JIA • These guidelines emphasized on the oligoarticular JIA-specific characteristics, severity factors, and treatment alternatives.
VEXAS syndrome is a rare, adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene. Patients may present with symptoms similar to IgG4-related disease (IgG4-RD) or systemic vasculitis. We report the case of a 70-year-old man who presented with periorbital swelling, fever, and elevated serum IgG4. However, a biopsy of the lacrimal gland did not show histological evidence of IgG4-RD. Consecutively, the patient developed progressive pulmonary infiltrations, bicytopenia and leukocytoclastic vasculitis. Chest-CT showed organizing pneumonia, which was histologically proven by transbronchial lung cryobiopsy (TBLC), again excluding IgG4-RD. PET/CT revealed hypermetabolic bone marrow and bone marrow aspiration biopsy showed vacuolization of granulocytic precursor cells. Finally, genetic testing for UBA1 mutation confirmed the diagnosis of VEXAS syndrome. Treatment with ruxolitinib in addition to steroids, led to temporary stabilization but long-term prognosis was unfavorable. This case highlights the importance of considering VEXAS syndrome a relevant differential diagnosis of vasculitis and IgG4-RD in men. Furthermore, we present valuable insights into the pathophysiology of VEXAS through transmission electron microscopy (TEM) of TBLC samples.