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Allergy Apr 2022A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long-acting β2 adrenergic bronchodilators... (Review)
Review
A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long-acting β2 adrenergic bronchodilators (LABA). The addition of long-acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single-inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS-LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive
PubMed: 34478578
DOI: 10.1111/all.15076 -
The Journal of Allergy and Clinical... Apr 2022Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear. (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis.
BACKGROUND
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear.
OBJECTIVE
We compared the effects of mAbs and aspirin desensitization (ASA-D) for treatment of CRSwNP.
METHODS
We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US Food and Drug Administration, and the European Medicines Agency databases from inception to August 4, 2021, for randomized controlled trials comparing the effects of mAbs and ASA-D for CRSwNP. We conducted network meta-analysis of sinusitis symptoms, heath-related quality of life, rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence. PROSPERO CRD42020177334.
RESULTS
Twenty-nine randomized controlled trials evaluating 8 treatments (n = 3461) were included in the network meta-analysis. Compared to placebo, moderate to high certainty evidence showed that health-related quality of life (SNOT-22) improved with dupilumab (mean difference [MD] -19.91 [95% confidence interval (CI) -22.50, -17.32]), omalizumab (MD -16.09 [95% CI -19.88, -12.30]), mepolizumab (MD -12.89 [95% CI -16.58, -9.19], ASA-D (MD -10.61 [95% CI -14.51, -6.71]), and benralizumab (MD -7.68 [95% CI -12.09, -3.27]). The risk of rescue nasal polyp surgery likely decreased with dupilumab (risk difference [RD] -16.35% [95% CI -18.13, -13.48]), omalizumab (RD -7.40% [95% CI -11.04, -2.43]), mepolizumab (RD -12.33% [95% CI -15.56, -7.22]), and ASA-D (RD -16.00% [95% CI -19.79, 0.21]; all moderate certainty). Comparisons among agents show with moderate to high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2 of 7, mepolizumab for 1 of 7, and ASA-D for 1 of 7.
CONCLUSIONS
Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents; dupilumab uniquely ranks among the most beneficial for all outcomes studied.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Aspirin; Chronic Disease; Humans; Nasal Polyps; Network Meta-Analysis; Omalizumab; Quality of Life; Sinusitis
PubMed: 34543652
DOI: 10.1016/j.jaci.2021.09.009 -
JAMA Surgery Apr 2021Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin allergy are less likely to prophylactically receive cefazolin and more likely to receive clindamycin or vancomycin, which results in higher rates of surgical site infections.
OBJECTIVE
To examine the incidence of dual allergy to cefazolin and natural penicillins.
DATA SOURCES
MEDLINE/PubMed, Web of Science, and Embase were searched without language restrictions for relevant articles published from database inception until July 31, 2020.
STUDY SELECTION
In this systematic review and meta-analysis, a search of MEDLINE/PubMed, Web of Science, and Embase was performed for articles published from database inception to July 31, 2020, for studies that included patients who had index allergies to a natural penicillin and were tested for tolerability to cefazolin or that included patients who had index allergies to cefazolin and were tested for tolerability to a natural penicillin. A total of 3228 studies were identified and 2911 were screened for inclusion.
DATA EXTRACTION AND SYNTHESIS
Data were independently extracted by 2 authors. Bayesian meta-analysis was used to estimate the frequency of allergic reactions.
MAIN OUTCOMES AND MEASURES
Dual allergy to cefazolin and a natural penicillin.
RESULTS
Seventy-seven unique studies met the eligibility criteria, yielding 6147 patients. Cefazolin allergy was identified in 44 participants with a history of penicillin allergy, resulting in a dual allergy meta-analytical frequency of 0.7% (95% credible interval [CrI], 0.1%-1.7%; I2 = 74.9%). Such frequency was lower for participants with unconfirmed (0.6%; 95% CrI, 0.1%-1.3%; I2 = 54.3%) than for those with confirmed penicillin allergy (3.0%; 95% CrI, 0.01%-17.0%; I2 = 88.2%). Thirteen studies exclusively assessed surgical patients (n = 3884), among whom 0.7% (95% CrI, 0%-3.3%; I2 = 85.5%) had confirmed allergy to cefazolin. Low heterogeneity was observed for studies of patients with unconfirmed penicillin allergy who had been exposed to perioperative cefazolin (0.1%; 95% CrI, 0.1%-0.3%; I2 = 13.1%). Penicillin allergy was confirmed in 16 participants with a history of cefazolin allergy, resulting in a meta-analytical frequency of 3.7% (95% CrI, 0.03%-13.3%; I2 = 64.4%). The frequency of penicillin allergy was 4.4% (95% CrI, 0%-23.0%; I2 = 75%) for the 8 studies that exclusively assessed surgical patients allergic to cefazolin.
CONCLUSIONS AND RELEVANCE
These findings suggest that most patients with a penicillin allergy history may safely receive cefazolin. The exception is patients with confirmed penicillin allergy in whom additional care is warranted.
Topics: Humans; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cefazolin; Drug Hypersensitivity; Incidence; Penicillins; Surgical Wound Infection
PubMed: 33729459
DOI: 10.1001/jamasurg.2021.0021 -
Clinical Microbiology and Infection :... Jun 2023Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic.
OBJECTIVES
To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis.
METHODS OF DATA SYNTHESIS
Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality.
DATA SOURCES
PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE.
STUDY ELIGIBILITY CRITERIA
Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022.
PARTICIPANTS
Adults who developed mucormycosis during or after COVID-19.
INTERVENTIONS
Patients with and without individual clinical variables were compared.
ASSESSMENT OF RISK OF BIAS
Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies.
RESULTS
Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780).
CONCLUSION
Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.
Topics: Adult; Humans; Aged; Mucormycosis; Coinfection; Pandemics; COVID-19; Hospitalization
PubMed: 36921716
DOI: 10.1016/j.cmi.2023.03.008 -
Dental and Medical Problems 2023Laser protocols for the treatment of dentin hypersensitivity (DH) have not yet been studied systematically. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Laser protocols for the treatment of dentin hypersensitivity (DH) have not yet been studied systematically.
OBJECTIVES
The present study aimed to review clinical trials on the treatment of DH with laser therapy through a systematic review and meta-analysis.
MATERIAL AND METHODS
The search of electronic databases resulted in 562 publications up to April 2020. The inclusion criteria were studies carried out on humans and reporting on the treatment of DH with laser therapy. Case reports, literature reviews and systematic reviews were excluded. Selected by abstract, potentially eligible papers were read in full (n = 160). Independent examiners performed data extraction and the assessment of the risk of bias.
RESULTS
A total of 34 studies were included in the analysis, and 11 in the quantitative analysis. It was observed that most studies followed up patients for a maximum of 6 months (55%). Through the meta-analysis, we observed statistically significant differences between the average pain before and after 3 months of treatment with highand low-power lasers. However, through indirect comparisons, it was observed that the high-power laser showed a greater tendency to reduce the pain levels after 3 months of treatment as compared to the low-power laser, but without a statistically significant difference.
CONCLUSIONS
It was possible to conclude that regardless of the type of laser used in the treatment of DH, this treatment is an effective option for the control of pain symptoms. However, it was not possible to establish a defined treatment protocol, since the evaluation methods are very different from each other. Text for Rewiew and clinical cases.
Topics: Humans; Dentin Sensitivity; Laser Therapy; Low-Level Light Therapy; Treatment Outcome; Lasers
PubMed: 37023343
DOI: 10.17219/dmp/151482 -
BMC Infectious Diseases Sep 2021Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia in school-age children. Macrolides are considered a first-line treatment for M.... (Meta-Analysis)
Meta-Analysis
Efficacy of tetracyclines and fluoroquinolones for the treatment of macrolide-refractory Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis.
BACKGROUND
Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia in school-age children. Macrolides are considered a first-line treatment for M. pneumoniae infection in children, but macrolide-refractory M. pneumoniae (MRMP) strains have become more common. In this study, we assessed the efficacy of tetracyclines and fluoroquinolones in MRMP treatment in children through a systematic review and meta-analysis.
METHODS
Two reviewers individually searched 10 electronic databases (Medline/Pubmed, Embase, the Cochrane Library, and core Korean, Chinese, and Japanese journals) for papers published from January 1, 1990 to March 8, 2018. The following data for each treatment group were extracted from the selected studies: intervention (tetracyclines and fluoroquinolones/comparator), patient characteristics (age and sex), and outcomes (fever duration, hospital stay length, treatment success rate, and defervescence rates 24, 48, and 72 h after starting treatment).
RESULTS
Eight studies involving 537 participants were included. Fever duration and hospital stay length were shorter in the tetracycline group than in the macrolide group (weighted mean difference [WMD] = - 1.45, 95% confidence interval [CI]: - 2.55 to - 0.36, P = 0.009; and WMD = - 3.33, 95% CI: - 4.32 to - 2.35, P < 0.00001, respectively). The therapeutic efficacy was significantly higher in the tetracycline group than in the macrolide group (odds ratio [OR]: 8.80, 95% CI: 3.12-24.82). With regard to defervescence rate, patients in the tetracycline group showed significant improvement compared to those in the macrolide group (defervescence rate after 24 h, OR: 5.34, 95% CI: 1.81-15.75; after 48 h, OR 18.37, 95% CI: 8.87-38.03; and after 72 h, OR: 40.77, 95% CI: 6.15-270.12). There were no differences in fever improvement within 24 h in patients in the fluoroquinolone group compared to those in the macrolide group (OR: 1.11, 95% CI: 0.25-5.00), although the defervescence rate was higher after 48 h in the fluoroquinolone group (OR: 2.78, 95% CI: 1.41-5.51).
CONCLUSION
Tetracyclines may shorten fever duration and hospital stay length in patients with MRMP infection. Fluoroquinolones may achieve defervescence within 48 h in patients with MRMP infection. However, these results should be carefully interpreted as only a small number of studies were included, and they were heterogeneous.
Topics: Anti-Bacterial Agents; Child; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Macrolides; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Tetracyclines
PubMed: 34563128
DOI: 10.1186/s12879-021-06508-7 -
The Cochrane Database of Systematic... Oct 2021Atopic eczema (AE), also known as atopic dermatitis, is a chronic inflammatory skin condition that causes significant burden. Phototherapy is sometimes used to treat AE... (Review)
Review
BACKGROUND
Atopic eczema (AE), also known as atopic dermatitis, is a chronic inflammatory skin condition that causes significant burden. Phototherapy is sometimes used to treat AE when topical treatments, such as corticosteroids, are insufficient or poorly tolerated.
OBJECTIVES
To assess the effects of phototherapy for treating AE.
SEARCH METHODS
We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and ClinicalTrials.gov to January 2021.
SELECTION CRITERIA
We included randomised controlled trials in adults or children with any subtype or severity of clinically diagnosed AE. Eligible comparisons were any type of phototherapy versus other forms of phototherapy or any other treatment, including placebo or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology. For key findings, we used RoB 2.0 to assess bias, and GRADE to assess certainty of the evidence. Primary outcomes were physician-assessed signs and patient-reported symptoms. Secondary outcomes were Investigator Global Assessment (IGA), health-related quality of life (HRQoL), safety (measured as withdrawals due to adverse events), and long-term control.
MAIN RESULTS
We included 32 trials with 1219 randomised participants, aged 5 to 83 years (mean: 28 years), with an equal number of males and females. Participants were recruited mainly from secondary care dermatology clinics, and study duration was, on average, 13 weeks (range: 10 days to one year). We assessed risk of bias for all key outcomes as having some concerns or high risk, due to missing data, inappropriate analysis, or insufficient information to assess selective reporting. Assessed interventions included: narrowband ultraviolet B (NB-UVB; 13 trials), ultraviolet A1 (UVA1; 6 trials), broadband ultraviolet B (BB-UVB; 5 trials), ultraviolet AB (UVAB; 2 trials), psoralen plus ultraviolet A (PUVA; 2 trials), ultraviolet A (UVA; 1 trial), unspecified ultraviolet B (UVB; 1 trial), full spectrum light (1 trial), Saalmann selective ultraviolet phototherapy (SUP) cabin (1 trial), saltwater bath plus UVB (balneophototherapy; 1 trial), and excimer laser (1 trial). Comparators included placebo, no treatment, another phototherapy, topical treatment, or alternative doses of the same treatment. Results for key comparisons are summarised (for scales, lower scores are better): NB-UVB versus placebo/no treatment There may be a larger reduction in physician-assessed signs with NB-UVB compared to placebo after 12 weeks of treatment (mean difference (MD) -9.4, 95% confidence interval (CI) -3.62 to -15.18; 1 trial, 41 participants; scale: 0 to 90). Two trials reported little difference between NB-UVB and no treatment (37 participants, four to six weeks of treatment); another reported improved signs with NB-UVB versus no treatment (11 participants, nine weeks of treatment). NB-UVB may increase the number of people reporting reduced itch after 12 weeks of treatment compared to placebo (risk ratio (RR) 1.72, 95% CI 1.10 to 2.69; 1 trial, 40 participants). Another trial reported very little difference in itch severity with NB-UVB (25 participants, four weeks of treatment). The number of participants with moderate to greater global improvement may be higher with NB-UVB than placebo after 12 weeks of treatment (RR 2.81, 95% CI 1.10 to 7.17; 1 trial, 41 participants). NB-UVB may not affect rates of withdrawal due to adverse events. No withdrawals were reported in one trial of NB-UVB versus placebo (18 participants, nine weeks of treatment). In two trials of NB-UVB versus no treatment, each reported one withdrawal per group (71 participants, 8 to 12 weeks of treatment). We judged that all reported outcomes were supported with low-certainty evidence, due to risk of bias and imprecision. No trials reported HRQoL. NB-UVB versus UVA1 We judged the evidence for NB-UVB compared to UVA1 to be very low certainty for all outcomes, due to risk of bias and imprecision. There was no evidence of a difference in physician-assessed signs after six weeks (MD -2.00, 95% CI -8.41 to 4.41; 1 trial, 46 participants; scale: 0 to 108), or patient-reported itch after six weeks (MD 0.3, 95% CI -1.07 to 1.67; 1 trial, 46 participants; scale: 0 to 10). Two split-body trials (20 participants, 40 sides) also measured these outcomes, using different scales at seven to eight weeks; they reported lower scores with NB-UVB. One trial reported HRQoL at six weeks (MD 2.9, 95% CI -9.57 to 15.37; 1 trial, 46 participants; scale: 30 to 150). One split-body trial reported no withdrawals due to adverse events over 12 weeks (13 participants). No trials reported IGA. NB-UVB versus PUVA We judged the evidence for NB-UVB compared to PUVA (8-methoxypsoralen in bath plus UVA) to be very low certainty for all reported outcomes, due to risk of bias and imprecision. There was no evidence of a difference in physician-assessed signs after six weeks (64.1% reduction with NB-UVB versus 65.7% reduction with PUVA; 1 trial, 10 participants, 20 sides). There was no evidence of a difference in marked improvement or complete remission after six weeks (odds ratio (OR) 1.00, 95% CI 0.13 to 7.89; 1 trial, 9/10 participants with both treatments). One split-body trial reported no withdrawals due to adverse events in 10 participants over six weeks. The trials did not report patient-reported symptoms or HRQoL. UVA1 versus PUVA There was very low-certainty evidence, due to serious risk of bias and imprecision, that PUVA (oral 5-methoxypsoralen plus UVA) reduced physician-assessed signs more than UVA1 after three weeks (MD 11.3, 95% CI -0.21 to 22.81; 1 trial, 40 participants; scale: 0 to 103). The trial did not report patient-reported symptoms, IGA, HRQoL, or withdrawals due to adverse events. There were no eligible trials for the key comparisons of UVA1 or PUVA compared with no treatment. Adverse events Reported adverse events included low rates of phototoxic reaction, severe irritation, UV burn, bacterial superinfection, disease exacerbation, and eczema herpeticum.
AUTHORS' CONCLUSIONS
Compared to placebo or no treatment, NB-UVB may improve physician-rated signs, patient-reported symptoms, and IGA after 12 weeks, without a difference in withdrawal due to adverse events. Evidence for UVA1 compared to NB-UVB or PUVA, and NB-UVB compared to PUVA was very low certainty. More information is needed on the safety and effectiveness of all aspects of phototherapy for treating AE.
Topics: Adult; Child; Dermatitis, Atopic; Eczema; Female; Humans; Male; Phototherapy; Quality of Life; Ultraviolet Therapy
PubMed: 34709669
DOI: 10.1002/14651858.CD013870.pub2 -
The Cochrane Database of Systematic... Mar 2022Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare, severe cutaneous adverse reactions usually triggered by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare, severe cutaneous adverse reactions usually triggered by medications. In addition to tertiary-level supportive care, various systemic therapies have been used including glucocorticoids, intravenous immunoglobulins (IVIGs), cyclosporin, N-acetylcysteine, thalidomide, infliximab, etanercept, and plasmapheresis. There is an unmet need to understand the efficacy of these interventions.
OBJECTIVES
To assess the effects of systemic therapies (medicines delivered orally, intramuscularly, or intravenously) for the treatment of SJS, TEN, and SJS/TEN overlap syndrome.
SEARCH METHODS
We searched the following databases up to March 2021: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five clinical trial registers, the reference lists of all included studies and of key review articles, and a number of drug manufacturer websites. We searched for errata or retractions of included studies.
SELECTION CRITERIA
We included only randomised controlled trials (RCTs) and prospective observational comparative studies of participants of any age with a clinical diagnosis of SJS, TEN, or SJS/TEN overlap syndrome. We included all systemic therapies studied to date and permitted comparisons between each therapy, as well as between therapy and placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as specified by Cochrane. Our primary outcomes were SJS/TEN-specific mortality and adverse effects leading to discontinuation of SJS/TEN therapy. Secondary outcomes included time to complete re-epithelialisation, intensive care unit length of stay, total hospital length of stay, illness sequelae, and other adverse effects attributed to systemic therapy. We rated the certainty of the evidence for each outcome using GRADE.
MAIN RESULTS
We included nine studies with a total of 308 participants (131 males and 155 females) from seven countries. We included two studies in the quantitative meta-analysis. We included three RCTs and six prospective, controlled observational studies. Sample sizes ranged from 10 to 91. Most studies did not report study duration or time to follow-up. Two studies reported a mean SCORe of Toxic Epidermal Necrosis (SCORTEN) of 3 and 1.9. Seven studies did not report SCORTEN, although four of these studies reported average or ranges of body surface area (BSA) (means ranging from 44% to 51%). Two studies were set in burns units, two in dermatology wards, one in an intensive care unit, one in a paediatric ward, and three in unspecified inpatient units. Seven studies reported a mean age, which ranged from 29 to 56 years. Two studies included paediatric participants (23 children). We assessed the results from one of three RCTs as low risk of bias in all domains, one as high, and one as some concerns. We judged the results from all six prospective observational comparative studies to be at a high risk of bias. We downgraded the certainty of the evidence because of serious risk of bias concerns and for imprecision due to small numbers of participants. The interventions assessed included systemic corticosteroids, tumour necrosis factor-alpha (TNF-alpha) inhibitors, cyclosporin, thalidomide, N-acetylcysteine, IVIG, and supportive care. No data were available for the main comparisons of interest as specified in the review protocol: etanercept versus cyclosporin, etanercept versus IVIG, IVIG versus supportive care, IVIG versus cyclosporin, and cyclosporin versus corticosteroids. Corticosteroids versus no corticosteroids It is uncertain if there is any difference between corticosteroids (methylprednisolone 4 mg/kg/day for two more days after fever had subsided and no new lesions had developed) and no corticosteroids on disease-specific mortality (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.72 to 9.03; 2 studies; 56 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. IVIG versus no IVIG It is uncertain if there is any difference between IVIG (0.2 to 0.5 g/kg cumulative dose over three days) and no IVIG in risk of disease-specific mortality (RR 0.33, 95% CI 0.04 to 2.91); time to complete re-epithelialisation (mean difference (MD) -2.93 days, 95% CI -4.4 to -1.46); or length of hospital stay (MD -2.00 days, 95% CI -5.81 to 1.81). All results in this comparison were based on one study with 36 participants, and very low-certainty evidence. Adverse effects leading to discontinuation of therapy were not reported. Etanercept (TNF-alpha inhibitor) versus corticosteroids Etanercept (25 mg (50 mg if weight > 65 kg) twice weekly "until skin lesions healed") may reduce disease-specific mortality compared to corticosteroids (intravenous prednisolone 1 to 1.5 mg/kg/day "until skin lesions healed") (RR 0.51, 95% CI 0.16 to 1.63; 1 study; 91 participants; low-certainty evidence); however, the CIs were consistent with possible benefit and possible harm. Serious adverse events, such as sepsis and respiratory failure, were reported in 5 of 48 participants with etanercept and 9 of 43 participants with corticosteroids, but it was not clear if they led to discontinuation of therapy. Time to complete re-epithelialisation and length of hospital stay were not reported. Cyclosporin versus IVIG It is uncertain if there is any difference between cyclosporin (3 mg/kg/day or intravenous 1 mg/kg/day until complete re-epithelialisation, then tapered off (10 mg/day reduction every 48 hours)) and IVIG (continuous infusion 0.75 g/kg/day for 4 days (total dose 3 g/kg) in participants with normal renal function) in risk of disease-specific mortality (RR 0.13, 95% CI 0.02 to 0.98, 1 study; 22 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. No studies measured intensive care unit length of stay.
AUTHORS' CONCLUSIONS
When compared to corticosteroids, etanercept may result in mortality reduction. For the following comparisons, the certainty of the evidence for disease-specific mortality is very low: corticosteroids versus no corticosteroids, IVIG versus no IVIG and cyclosporin versus IVIG. There is a need for more multicentric studies, focused on the most important clinical comparisons, to provide reliable answers about the best treatments for SJS/TEN.
Topics: Acetylcysteine; Adrenal Cortex Hormones; Adult; Autoimmune Diseases; Child; Cyclosporine; Etanercept; Female; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Observational Studies as Topic; Stevens-Johnson Syndrome; Thalidomide; Tumor Necrosis Factor-alpha
PubMed: 35274741
DOI: 10.1002/14651858.CD013130.pub2 -
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 -
The Journal of Allergy and Clinical... May 2023Antidrug antibodies (ADAs) may worsen the efficacy and safety of biologics. However, little is known about the incidence of ADAs associated with the 6 biologics approved... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antidrug antibodies (ADAs) may worsen the efficacy and safety of biologics. However, little is known about the incidence of ADAs associated with the 6 biologics approved for the treatment of asthma in the United States.
OBJECTIVE
To elucidate the incidence of ADAs and their impact on reported clinical outcomes.
METHODS
Systematic review and meta-analyses of randomized controlled trials, open-label extension studies, and nonrandomized studies of biologics in patients with asthma indexed in PubMed, Embase, and CENTRAL between January 1, 2000, and July 9, 2022, were carried out. The primary outcomes were treatment-emergent ADAs (incidence) and ADA prevalence.
RESULTS
A total of 46 studies met the eligibility criteria. ADA incidence over follow-up was 2.91% (95% CI, 1.60-4.55) and was highest in the benralizumab studies (8.35%), with a risk ratio of 4.9 (2.69-8.92) when compared with placebo, and lowest in the omalizumab studies (0.00%). Incidence was 7.61% in the dupilumab studies, 4.39% in reslizumab, 3.63% in mepolizumab, and 1.12% in the tezepelumab studies. Incidence of neutralizing antibodies was 0.00% to 10.74% and was highest for benralizumab (7.12%). Incidence of neutralizing antibodies was higher in the benralizumab every 8 weeks (8.17%) versus every 4 weeks arms (5.81%). Results were consistent in subgroup analyses by study type and length of follow-up.
CONCLUSIONS
Approximately 2.9% of individuals in the included studies developed ADAs over study follow-up period. The incidence was highest in the benralizumab group and lowest in the omalizumab group. The subcutaneous route and longer dosing intervals were associated with higher ADA development.
Topics: Humans; Antibodies, Monoclonal; Omalizumab; Incidence; Asthma; Biological Products; Antibodies, Neutralizing; Anti-Asthmatic Agents
PubMed: 36716995
DOI: 10.1016/j.jaip.2022.12.046