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Aging Cell Jul 2023Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains... (Meta-Analysis)
Meta-Analysis Review
Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length.
Topics: Humans; Mendelian Randomization Analysis; Arthritis, Rheumatoid; Glioma; Hypertension; Telomere; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37232505
DOI: 10.1111/acel.13874 -
Annals of the Rheumatic Diseases Oct 2023Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most...
The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the of diagnosis, treatment and monitoring of HLH/MAS.
METHODS
A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS.
RESULTS
The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.
CONCLUSION
These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.
Topics: Child; Adult; Humans; United States; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Rheumatology; Consensus
PubMed: 37487610
DOI: 10.1136/ard-2023-224123 -
Clinical Rheumatology Sep 2023Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality... (Review)
Review
Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality CPG recommendations, highlighting areas of consistency, and inconsistency. Electronic searches of five databases and four online guideline repositories were performed. RA management CPGs were eligible for inclusion if they were written in English and published between January 2015 and February 2022; focused on adults ≥ 18 years of age; met the criteria of a CPG as defined by the Institute of Medicine; and were rated as high quality on the Appraisal of Guidelines for Research and Evaluation II instrument. RA CPGs were excluded if they required additional payment to access; only addressed recommendations for the system/organization of care and did not include interventional management recommendations; and/or included other arthritic conditions. Of 27 CPGs identified, 13 CPGs met eligibility criteria and were included. Non-pharmacological care should include patient education, patient-centered care, shared decision-making, exercise, orthoses, and a multi-disciplinary approach to care. Pharmacological care should include conventional synthetic disease modifying anti-rheumatic drugs (DMARDs), with methotrexate as the first-line choice. If monotherapy conventional synthetic DMARDs fail to achieve a treatment target, this should be followed by combination therapy conventional synthetic DMARDs (leflunomide, sulfasalazine, hydroxychloroquine), biologic DMARDS and targeted synthetic DMARDS. Management should also include monitoring, pre-treatment investigations and vaccinations, and screening for tuberculosis and hepatitis. Surgical care should be recommended if non-surgical care fails. This synthesis offers clear guidance of evidence-based RA care to healthcare providers. TRIAL REGISTRATION: The protocol for this review was registered with Open Science Framework ( https://doi.org/10.17605/OSF.IO/UB3Y7 ).
Topics: Adult; Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Hydroxychloroquine; Methotrexate; Sulfasalazine; Practice Guidelines as Topic
PubMed: 37291382
DOI: 10.1007/s10067-023-06654-0 -
Annals of Medicine Dec 2023Although there is an assertion that weather conditions affect osteoarthritis (OA) pain, the results from clinical studies remain inconsistent. This meta-analysis was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although there is an assertion that weather conditions affect osteoarthritis (OA) pain, the results from clinical studies remain inconsistent. This meta-analysis was performed to evaluate the association between weather conditions and OA pain.
METHODS
Cochrane Library, Embase, PubMed, and Web of Science were searched from inception to September 30, 2022. Observational studies that explored all weather conditions associated with pain intensity were included. In the systematic review, the methodological quality of the selected studies was assessed and a best-evidence synthesis was used to make qualitative conclusions. Based on homogeneous results, Fisher's scores derived from the effect size of temperature (T), barometric pressure (BP) or relative humidity (RH) related to OA pain were synthesized and further transformed to the correlation coefficients (summary r) in meta-analysis.
RESULTS
A total of 14 studies were included in the best-evidence synthesis of a qualitative systematic review. There was strong evidence with 13 of 14 studies reporting consistent findings that weather factors in general, including any kind of meteorological condition, were associated with OA pain. Subsequently, 3 studies regarding BP or T, and 5 studies regarding RH with the pain of OA were included in quantitative meta-analyses. Both BP (pooled Fisher's = 0.37, 95% CI 0.15 to 0.59; summary = 0.35, 95% CI 0.15 to 0.53) and RH (pooled Fisher's = 0.10, 95% CI 0.01 to 0.18; summary = 0.086, 95% CI -0.05 to 0.22) were positively related to OA pain, while T was negatively related to OA pain (pooled Fisher's = -0.38, 95% CI -0.60 to -0.16; summary = -0.36, 95% CI -0.54 to -0.16).
CONCLUSIONS
In this study, weather factors in general were significantly associated with OA pain. It may provide useful references for the daily health management of OA. More studies designed with the consistent meteorological condition are warranted to validate the findings.KEY MESSAGEMany people with osteoarthritis think their joint pain is affected by the weather, while the association between OA pain and weather conditions is still unclear.This is a systematic review and meta-analysis of 14 observational studies for the association between weather conditions and OA pain.Weather conditions appear to be associated with OA pain. Barometric pressure and relative humidity were positively correlated to OA pain intensity, while temperature was negatively correlated to OA pain.
Topics: Humans; Osteoarthritis; Pain; Weather; Temperature; Observational Studies as Topic
PubMed: 37078741
DOI: 10.1080/07853890.2023.2196439 -
The Lancet. Neurology Aug 2023Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by...
BACKGROUND
Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by 2030, and assessing trends in the global meningitis burden can help track progress and identify gaps in achieving these goals. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we aimed to assess incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990 to 2019, for 204 countries and territories.
METHODS
We modelled meningitis mortality using vital registration, verbal autopsy, sample-based vital registration, and mortality surveillance data. Meningitis morbidity was modelled with a Bayesian compartmental model, using data from the published literature identified by a systematic review, as well as surveillance data, inpatient hospital admissions, health insurance claims, and cause-specific meningitis mortality estimates. For aetiology estimation, data from multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature studies were analysed by use of a network analysis model to estimate the proportion of meningitis deaths and cases attributable to the following aetiologies: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Staphylococcus aureus, viruses, and a residual other pathogen category.
FINDINGS
In 2019, there were an estimated 236 000 deaths (95% uncertainty interval [UI] 204 000-277 000) and 2·51 million (2·11-2·99) incident cases due to meningitis globally. The burden was greatest in children younger than 5 years, with 112 000 deaths (87 400-145 000) and 1·28 million incident cases (0·947-1·71) in 2019. Age-standardised mortality rates decreased from 7·5 (6·6-8·4) per 100 000 population in 1990 to 3·3 (2·8-3·9) per 100 000 population in 2019. The highest proportion of total all-age meningitis deaths in 2019 was attributable to S pneumoniae (18·1% [17·1-19·2]), followed by N meningitidis (13·6% [12·7-14·4]) and K pneumoniae (12·2% [10·2-14·3]). Between 1990 and 2019, H influenzae showed the largest reduction in the number of deaths among children younger than 5 years (76·5% [69·5-81·8]), followed by N meningitidis (72·3% [64·4-78·5]) and viruses (58·2% [47·1-67·3]).
INTERPRETATION
Substantial progress has been made in reducing meningitis mortality over the past three decades. However, more meningitis-related deaths might be prevented by quickly scaling up immunisation and expanding access to health services. Further reduction in the global meningitis burden should be possible through low-cost multivalent vaccines, increased access to accurate and rapid diagnostic assays, enhanced surveillance, and early treatment.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Child; Humans; Global Burden of Disease; Bayes Theorem; Meningitis; Risk Factors; Global Health
PubMed: 37479374
DOI: 10.1016/S1474-4422(23)00195-3 -
Journal of Sport and Health Science Jul 2024Impairments in hamstring strength, flexibility, and morphology have been associated with altered knee biomechanics, pain, and function. Determining the presence of these... (Meta-Analysis)
Meta-Analysis Review
There is more to the knee joint than just the quadriceps: A systematic review with meta-analysis and evidence gap map of hamstring strength, flexibility, and morphology in individuals with gradual-onset knee disorders.
BACKGROUND
Impairments in hamstring strength, flexibility, and morphology have been associated with altered knee biomechanics, pain, and function. Determining the presence of these impairments in individuals with gradual-onset knee disorders is important and may indicate targets for assessment and rehabilitation. This systematic review aimed to synthesize the literature to determine the presence of impairments in hamstring strength, flexibility, and morphology in individuals with gradual-onset knee disorders.
METHODS
Five databases (MEDLINE, Embase, CINAHL, SPORTDiscus, and Web of Science) were searched from inception to September 2022. Only studies comparing hamstring outcomes (e.g., strength, flexibility, and/or morphology) between individuals with gradual-onset knee disorders and their unaffected limbs or pain-free controls were included. Meta-analyses for each knee disorder were performed. Outcome-level certainty was assessed using the Grading of Recommendations Assessment, Development, and Evaluation, and evidence gap maps were created.
RESULTS
Seventy-nine studies across 4 different gradual-onset knee disorders (i.e., knee osteoarthritis (OA), patellofemoral pain (PFP), chondromalacia patellae, and patellar tendinopathy) were included. Individuals with knee OA presented with reduced hamstring strength compared to pain-free controls during isometric (standard mean difference (SMD) = -0.76, 95% confidence interval (95%CI) : -1.32 to -0.21) and concentric contractions (SMD = -0.97, 95%CI : -1.49 to -0.45). Individuals with PFP presented with reduced hamstring strength compared to pain-free controls during isometric (SMD = -0.48, 95%CI : -0.82 to -0.14), concentric (SMD = -1.07, 95%CI : -2.08 to -0.06), and eccentric contractions (SMD = -0.59, 95%CI : -0.97 to -0.21). No differences were observed in individuals with patellar tendinopathy. Individuals with PFP presented with reduced hamstring flexibility when compared to pain-free controls (SMD = -0.76, 95%CI : -1.15 to -0.36). Evidence gap maps identified insufficient evidence for chondromalacia patellae and hamstring morphology across all gradual-onset knee disorders.
CONCLUSION
Our findings suggest that assessing and targeting impairments in hamstring strength and flexibility during rehabilitation may be recommended for individuals with knee OA or PFP.
Topics: Humans; Muscle Strength; Hamstring Muscles; Knee Joint; Quadriceps Muscle; Osteoarthritis, Knee; Patellofemoral Pain Syndrome; Range of Motion, Articular; Biomechanical Phenomena; Chondromalacia Patellae; Evidence Gaps
PubMed: 37669706
DOI: 10.1016/j.jshs.2023.08.004 -
Arthritis & Rheumatology (Hoboken, N.J.) Oct 2023Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most...
The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS.
METHODS
A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS.
RESULTS
The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.
CONCLUSION
These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.
Topics: Adult; Child; Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Consensus; Physicians; Advisory Committees
PubMed: 37486733
DOI: 10.1002/art.42636 -
Annals of the Rheumatic Diseases May 2024New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the...
OBJECTIVE
New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA.
METHODS
Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined.
RESULTS
The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed.
CONCLUSION
These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.
Topics: Arthritis, Psoriatic; Humans; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Methotrexate; Biological Products
PubMed: 38499325
DOI: 10.1136/ard-2024-225531 -
Arthritis Care & Research Sep 2023To evaluate the quality of clinical practice guidelines (CPGs) for interventions in management of osteoarthritis (OA) and to provide a synthesis of high-quality CPG...
OBJECTIVE
To evaluate the quality of clinical practice guidelines (CPGs) for interventions in management of osteoarthritis (OA) and to provide a synthesis of high-quality CPG recommendations.
METHODS
Five databases (OvidSP Medline, Cochrane, Cumulative Index to Nursing and Allied Health Literature [CINAHL], Embase, and the Physiotherapy Evidence Database [PEDro]) and 4 online guideline repositories were searched. CPGs for the management of OA were included if they were 1) written in English and published from January 2015 to February 2022, focused on adults age ≥18 years, and met the criteria of a CPG as defined by the Institute of Medicine; and 2) were rated as high quality on the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. CPGs for OA were excluded if they were available via institutional access only, only addressed recommendations for the system/organization of care and did not include interventional management recommendations, and/or included other arthritic conditions.
RESULTS
Of 20 eligible CPGs, 11 were appraised as high quality and included in the synthesis. Of interest were the hip, knee, hand, and glenohumeral joints and/or polyarticular OA. Consistent recommendations were that care should be patient centered and include exercise, education, and weight loss (where appropriate). Nonsteroidal antiinflammatory drugs and surgical interventions were recommended for disabling OA that had not improved with nonsurgical care. Hand orthoses should be recommended for patients with hand OA.
CONCLUSION
This synthesis of high-quality CPGs for OA management offers health care providers with clear, simple guidance of recommended OA care to improve patient outcomes.
Topics: Humans; Adolescent; Osteoarthritis; Physical Therapy Modalities; Hand; Knee Joint; Lower Extremity
PubMed: 36762545
DOI: 10.1002/acr.25101 -
Respiratory Medicine Sep 2023The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) ranges from asymptomatic findings on radiographic imaging to a rapidly progressive illness leading to respiratory failure and death. The treatment is always challenging due to the paucity of proven effective treatments. Nintedanib and pirfenidone are recently approved antifibrotics in idiopathic pulmonary fibrosis. This study aimed to investigate the efficacy and safety of antifibrotic agents in the treatment of CTD-ILD and RA-ILD.
METHODS
Relevant databases were searched for randomized controlled trials that compared pirfenidone or nintedanib with placebo in patients with CTD-ILD and RA-ILD. The primary outcome was the change in forced vital capacity (FVC). The odds ratio or risk ratio with 95% confidence interval (CI) was estimated for categorical data, and the mean difference with 95% CI was estimated for continuous data. The I statistic was used to assess heterogeneity, and meta-analysis was performed when possible.
RESULTS
Ten studies with a total of 880 participants met the inclusion criteria. Of these, four studies were included in the meta-analysis. According to the pooled result, the annual decline of FVC was significantly decreased in the antifibrotic agent arm compared to that in the placebo arm (MD 70.58 mL/yr, 95% CI 40.55 to 100.61).
CONCLUSION
This review suggests a potential benefit and safety of antifibrotic treatment in slowing the decline of FVC in patients with CTD-ILD and RA-ILD. Further large-sample, random-controlled, high-quality trials are needed to provide more evidence in the decision-making regarding the use of antifibrotics in this group of patients.
CLINICAL TRIAL REGISTRATION
PROSPERO; No: CRD42022369112; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Antifibrotic Agents; Lung Diseases, Interstitial; Connective Tissue Diseases; Idiopathic Pulmonary Fibrosis; Vital Capacity
PubMed: 37315742
DOI: 10.1016/j.rmed.2023.107329