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The European Respiratory Journal Dec 2023Bedaquiline resistance is a major threat to drug-resistant tuberculosis control strategies. This analysis found a pooled prevalence of baseline bedaquiline resistance of... (Meta-Analysis)
Meta-Analysis
Bedaquiline resistance is a major threat to drug-resistant tuberculosis control strategies. This analysis found a pooled prevalence of baseline bedaquiline resistance of 2.4% and a pooled prevalence of treatment-emergent bedaquiline resistance of 2.1%. https://bit.ly/3FC6yio
Topics: Humans; Diarylquinolines; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Mycobacterium tuberculosis
PubMed: 37945030
DOI: 10.1183/13993003.00639-2023 -
BMJ Open Nov 2023Head-to-head clinical trials are common in psoriasis, but scarce in psoriatic arthritis (PsA), making treatment comparisons between therapeutic classes difficult. This... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Head-to-head clinical trials are common in psoriasis, but scarce in psoriatic arthritis (PsA), making treatment comparisons between therapeutic classes difficult. This study describes the relative effectiveness of targeted synthetic (ts) and biologic (b) disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes (PROs) through network meta-analysis (NMA).
DESIGN
A systematic literature review (SLR) was conducted in January 2020. Bayesian NMAs were conducted to compare treatments on Health Assessment Questionnaire Disability Index (HAQ-DI) and 36-item Short Form (SF-36) Health Survey including Mental Component Summary (MCS) and Physical Component Summary (PCS) scores.
DATA SOURCES
Ovid MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily),Embase and Cochrane Central Register of Controlled Trials.
ELIGIBILITY CRITERIA
Phase III randomised controlled trials (RCTs) evaluating patients with PsA receiving tsDMARDS, bDMARDs or placebo were included in the SLR; there was no restriction on outcomes.
DATA EXTRACTION AND SYNTHESIS
Two independent researchers reviewed all citations. Data for studies meeting all inclusion criteria were extracted into a standardised Excel-based form by one reviewer and validated by a second reviewer. A third reviewer was consulted to resolve any discrepancies, as necessary. Risk of bias was assessed using the The National Institute for Health and Care Excellence clinical effectiveness quality assessment checklist.
RESULTS
In total, 26 RCTs were included. For HAQ-DI, SF-36 PCS and SF-36 MCS scores, intravenous tumour necrosis factor (TNF) alpha inhibitors generally ranked higher than most other classes of therapies available to treat patients with PsA. For almost all outcomes, several interleukin (IL)-23, IL-17A, subcutaneous TNF and IL-12/23 agents offered comparable improvement, while cytotoxic T-lymphocyte-associated antigen 4, phosphodiesterase-4 and Janus kinase inhibitors often had the lowest efficacy.
CONCLUSIONS
While intravenous TNFs may provide some improvements in PROs relative to several other tsDMARDs and bDMARDs for the treatment of patients with PsA, differences between classes of therapies across outcomes were small.
Topics: Humans; Arthritis, Psoriatic; Antibodies, Monoclonal; Network Meta-Analysis; Antirheumatic Agents; Patient Reported Outcome Measures
PubMed: 37940157
DOI: 10.1136/bmjopen-2022-062306 -
Frontiers in Medicine 2023Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug,...
BACKGROUND
Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug, oxcarbazepine, may cause Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). However, the clinical features of oxcarbazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) remain ambiguous. This article aims to explore the clinical features of SJS/TEN.
METHODS
Systematic searches of several Chinese and English databases were conducted for case reports published on PubMed, EMBASE, Web of Science, MEDLINE, CNKI from January 1, 2007 to March 1, 2023.
RESULTS
A total of seventeen patients (10 males and 7 females) were included in this study, including nine adult patients and eight pediatric patients. The results showed that males seem to have a higher prevalence of SJS/TEN than females, and SJS/TEN usually occurs within 2 weeks after administration of oxcarbazepine (OXC). The main clinical manifestations among the included patients were rashes or maculopapules (17 cases, 100%), fever (11 cases, 64.7%), mucosal lesions (15 cases, 88.2%), conjunctivitis with/without ocular discharge (12 cases, 70.6%), and blisters (12 cases, 70.6%). After stopping OXC or switching to other drugs that treat primary disease as well as treatment with IVIG, glucocorticoid, anti-allergy, and fluid replacement, eight of the included patients recovered completely, and another eight of the included patients reported symptomatic improvement, while the prognosis of one of the included patients was not reported.
CONCLUSION
Diverse clinical signs and symptoms of SJS/TEN might result in misinterpretation and delayed diagnosis. It should be identified and treated immediately to avoid significant consequences and potentially jeopardize patients' lives.
PubMed: 37881633
DOI: 10.3389/fmed.2023.1232969 -
European Respiratory Review : An... Dec 2023We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other treatments or placebo.
METHODS
Protocol registration CRD42020216098 (www.crd.york.ac.uk/PROSPERO). MEDLINE and Embase databases were used to conduct the search. Two authors independently selected studies and extracted data, and a third reviewer resolved discrepancies. Meta-analyses were constructed to estimate the standardised mean difference (SMD) using a random-effects model.
RESULTS
Out of 3937 articles identified, 49 studies met the inclusion criteria, mostly randomised clinical trials (sample sizes: 21-689 patients). The SMD of change pooled estimators for the global, mental and physical domains of health-related quality of life were not statistically significant. For daytime and night-time symptoms scores, the SMD (95% CI) was in favour of inhaled corticosteroids (-0.12, -0.20- -0.05 and -0.23, -0.41- -0.06, respectively). The pooled estimator for global asthma symptoms was better for montelukast when compared with placebo (0.90, 0.44-1.36).
CONCLUSIONS
The synthesis of the available evidence suggests that, in children and adolescents, montelukast was effective in controlling asthma symptoms when compared with placebo, but inhaled corticosteroids were superior in controlling symptoms, especially at night-time. These findings of our systematic review concur with current guidelines for asthma treatment.
Topics: Adolescent; Humans; Child; Quality of Life; Asthma; Rhinitis, Allergic; Adrenal Cortex Hormones
PubMed: 37852659
DOI: 10.1183/16000617.0124-2023 -
Frontiers in Public Health 2023The COVID-19 pandemic focused attention on healthcare disparities and inequities faced by individuals within marginalized and structurally disadvantaged groups in the...
INTRODUCTION
The COVID-19 pandemic focused attention on healthcare disparities and inequities faced by individuals within marginalized and structurally disadvantaged groups in the United States. These individuals bore the heaviest burden across this pandemic as they faced increased risk of infection and difficulty in accessing testing and medical care. Individuals experiencing housing insecurity are a particularly vulnerable population given the additional barriers they face. In this scoping review, we identify some of the barriers this high-risk group experienced during the early days of the pandemic and assess novel solutions to overcome these barriers.
METHODS
A scoping review was performed following PRISMA-Sc guidelines looking for studies focusing on COVID-19 testing among individuals experiencing housing insecurity. Barriers as well as solutions to barriers were identified as applicable and summarized using qualitative methods, highlighting particular ways that proved effective in facilitating access to testing access and delivery.
RESULTS
Ultimately, 42 studies were included in the scoping review, with 143 barriers grouped into four categories: lack of cultural understanding, systemic racism, and stigma; medical care cost, insurance, and logistics; immigration policies, language, and fear of deportation; and other. Out of these 42 studies, 30 of these studies also suggested solutions to address them.
CONCLUSION
A paucity of studies have analyzed COVID-19 testing barriers among those experiencing housing insecurity, and this is even more pronounced in terms of solutions to address those barriers. Expanding resources and supporting investigators within this space is necessary to ensure equitable healthcare delivery.
Topics: Humans; United States; COVID-19 Testing; COVID-19; Pandemics; Housing Instability; Emigration and Immigration
PubMed: 37841714
DOI: 10.3389/fpubh.2023.1237066 -
PloS One 2023Biosimilars are increasingly available for the treatment of many serious disorders, however some concerns persist about switching a patient to a biosimilar whose... (Meta-Analysis)
Meta-Analysis
Biosimilars are increasingly available for the treatment of many serious disorders, however some concerns persist about switching a patient to a biosimilar whose condition is stable while on the reference biologic. Randomized controlled studies and extension studies with a switch treatment period (STP) to or from a biosimilar and its reference biologic were identified from publicly available information maintained by the U.S. Food and Drug Administration (FDA). These findings were augmented with data from peer reviewed publications containing information not captured in FDA reviews. Forty-four STPs were identified from 31 unique studies for 21 different biosimilars. Data were extracted and synthesized following PRISMA guidelines. Meta-analysis was conducted to estimate the overall risk difference across studies. A total of 5,252 patients who were switched to or from a biosimilar and its reference biologic were identified. Safety data including deaths, serious adverse events, and treatment discontinuation showed an overall risk difference (95% CI) of -0.00 (-0.00, 0.00), 0.00 (-0.01, 0.01), -0.00 (-0.01, 0.00) across STPs, respectively. Immunogenicity data showed similar incidence of anti-drug antibodies and neutralizing antibodies in patients within a STP who were switched to or from a biosimilar to its reference biologic and patients who were not switched. Immune related adverse events such as anaphylaxis, hypersensitivity reactions, and injections site reactions were similar in switched and non-switched patients. This first systematic review using statistical methods to address the risk of switching patients between reference biologics and biosimilars finds no difference in the safety profiles or immunogenicity rates in patients who were switched and those who remained on a reference biologic or a biosimilar.
Topics: Humans; Biosimilar Pharmaceuticals; Biological Factors; Research Design; Anaphylaxis; Antibodies
PubMed: 37788264
DOI: 10.1371/journal.pone.0292231 -
The Journal of Allergy and Clinical... Nov 2023To improve β-lactam delabeling outcomes, we need to understand current practice and the evidence base regarding its outcomes, safety, and impact.
BACKGROUND
To improve β-lactam delabeling outcomes, we need to understand current practice and the evidence base regarding its outcomes, safety, and impact.
OBJECTIVES
We sought to assess the existing published evidence reporting on the effectiveness of penicillin allergy testing and delabeling.
METHODS
We conducted a systematic review of studies reporting β-lactam delabeling practices and outcomes after testing, including β-lactam use and patient understanding of the delabeling result. Searches of the PubMed, Scopus, and Embase databases; clinical trial registries; and websites of professional organizations were conducted. Data were extracted from the included studies in duplicate, with a third extraction if discrepancies remained.
RESULTS
We included 284 publications (covering 98,316 participants); 173 were prospective studies, with no randomized controlled trials. The overall study quality was low. In all, 95.6% of individuals who underwent provocation testing were delabeled. Factors associated with successful delabeling could not be determined because of significant heterogeneity between studies. Anaphylaxis due to testing occurred in 0.3% of participants (95 of 31,667). Subjects who did not undergo skin testing (6,980 patients in 31 studies) before challenge had higher rates of provocation test positivity (8.8% vs 4.1% [ < .0001]) and anaphylaxis (15.9% vs 2.7% [ < .0001]) than those subjects who underwent skin testing (51,607 patients in 177 studies). Six studies (2.1%) followed patients after testing to assess their adherence to prescribing recommendations. In all, 136 participants (20.6%) were actively avoiding β-lactams despite delabeling.
CONCLUSIONS
The available data suggest that penicillin allergy testing is safe and effective in delabeling most individuals, but the evidence base is incomplete and more work is required to assess the role of skin testing and the impact that delabeling is having on prescribing habits.
PubMed: 37781667
DOI: 10.1016/j.jacig.2023.100160 -
The World Allergy Organization Journal Sep 2023Beta-lactams (BLs) are the most prescribed antibiotics, being the most frequent cause of drug allergy. However, the association between BL allergy and genetic variations...
IMPORTANCE
Beta-lactams (BLs) are the most prescribed antibiotics, being the most frequent cause of drug allergy. However, the association between BL allergy and genetic variations is still unclear.
OBJECTIVE
This systematic review and meta-analysis aimed to summarize the genetic effects of BL-induced hypersensitivity using existing evidence.
METHODS
We searched PubMed, Medline, Scopus, EMBASE, CINAHL, and Cochrane Library from inception to September 15, 2022 with no language restriction. Genetic association studies investigating genetic variant/polymorphism and risk of drug-induced hypersensitivity reactions among individuals receiving BL-antibiotics were included. We excluded studies of acute interstitial nephritis, drug-induced liver injury, serum sickness, and isolated drug fever. Data were comprehensively synthesized and quality of study were assessed using STrengthening the Reporting of Genetic Association Studies (STREGA). The record screening, extraction and quality assessment were performed by two reviewers and discussions were made to resolve discrepancies. The effects of each variant were pooled and evaluated by modified Venice criteria.
RESULTS
A total of 9276 records were identified, and 31 studies were eligible for inclusion. Twenty-seven were candidate-gene association studies (5416 cases and 5939 controls), while the others were next-generation sequencing (NGS) or genome-wide association studies (GWASs) (119 838 cases and 1 487 111 controls). Forty-nine polymorphisms were identified and most of them located in allergic reaction pathways. Meta-analyses of 15 candidate variants in a mixture of both immediate and non-immediate reactions revealed weak genetic effects of rs1801275 (8 studies; n = 1,560; odd ratio 0.73; 95%CI: 0.57-0.93) and rs20541 (4 studies; n = 1,482; odd ratio 1.34; 95%CI: 1.07-1.68) in and , respectively. Results from GWASs and NGS identified, and confirmed associations in HLA regions including and .
CONCLUSION
Our study summarized genetic evidence influencing BL-induced hypersensitivity and estimated effects of potential variants. We postulated that the genomic studies provide better insights to the mechanism of reactions and suggest potential effects of HLA Class II variants. However, results were inconsistent and unable to generalize in different settings. Further high-throughput studies with a well-defined function, epigenetic interaction, incorporated with clinical factors, would be beneficial for risk identification in BL-induced hypersensitivity.
PubMed: 37780578
DOI: 10.1016/j.waojou.2023.100816 -
Journal of the Academy of... 2023Tacrolimus is the most common immunosuppressant used after transplant, yet it can result in moderate-to-severe neurotoxicity in up to 32% of patients. Signs of... (Review)
Review
BACKGROUND
Tacrolimus is the most common immunosuppressant used after transplant, yet it can result in moderate-to-severe neurotoxicity in up to 32% of patients. Signs of neurotoxicity can vary from mild (tremor or headache) to severe (posterior reversible encephalopathy syndrome or psychosis. Prompt recognition and management is needed to lead to symptom resolution.
OBJECTIVE
The objective of this study is to describe the clinical presentation of tacrolimus-induced psychosis, a type of tacrolimus-inducted neurotoxicity, and distinguish it from other central nervous system disturbances, including delirium.
METHODS AND RESULTS
We present a case of delayed onset tacrolimus-induced psychosis with focus on unique clinical features and management strategies. We conducted a systematic review of cases of tacrolimus-induced psychosis using the PubMed database and included 15 manuscripts in our review.
CONCLUSIONS
Tacrolimus-induced psychosis is a unique presentation of tacrolimus-related neurotoxicity and can present without the cardinal symptoms of delirium. The data on isolated psychotic symptoms are limited with current literature focusing on more common presentations of tacrolimus-induced neurotoxicity, such as delirium and tremor. Development of psychosis can occur later in the treatment course and at normal tacrolimus serum levels. It can improve with antipsychotic therapies, but primary management should include cross-titration to an alternate immunosuppressant regimen.
Topics: Humans; Tacrolimus; Tremor; Posterior Leukoencephalopathy Syndrome; Immunosuppressive Agents; Psychotic Disorders; Neurotoxicity Syndromes; Lung Transplantation; Delirium
PubMed: 37778461
DOI: 10.1016/j.jaclp.2023.09.002 -
Seminars in Arthritis and Rheumatism Dec 2023Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard... (Review)
Review
INTRODUCTION
Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard of care'. Our aim was to examine the safety and efficacy of local, non-surgical treatment for SSc-DUs.
METHODS
A systematic literature review (SLR) of original research articles up to August, 29 2022 was performed according to the PICO framework. References were independently screened by two reviewers and risk of bias was assed using validated tools. Due to study heterogeneity narrative summaries are used to present data.
RESULTS
Among 899 retrieved references, 14 articles were included (2 randomised trials (RTs), and 12 observational (OBS) studies). The most frequently studied procedure (5 studies) was botulin A toxin (hand or single finger) injection with a reported healing rate (HR) of 71%-100%. Amniotic and hydrocolloid membranes were examined in one study each and associated with a good HR. Tadalafil 2% cream was studied in a single study with a reduction in the number of DUs. Vitamin E gel was associated with a reduction in ulcer healing time. Low-level light therapy, hydrodissection and corticosteroid injection, extracorporeal shock wave (ESW) and photobiomodulation were evaluated in a single study each and showed a positive trend. Dimethyl sulfoxide was associated with significant local toxicity.
CONCLUSIONS
A range of non-surgical, local treatments for SSc-DUs have been explored and showed efficacy to some extent. We have identified methodological flaws that should be avoided in the design of future studies to explore locally-acting treatments for SSc-DUs.
Topics: Humans; Skin Ulcer; Fingers; Hand; Scleroderma, Systemic
PubMed: 37778090
DOI: 10.1016/j.semarthrit.2023.152267