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BACKGROUND: Systemic treatments for atopic dermatitis (AD) are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and network meta-analysis (NMA), we previously analysed continuous efficacy measures. OBJECTIVES: To compare binary efficacy outcomes of systemic treatments for AD. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American and Caribbean Health Science Information (LILACS) database, Global Resource for Eczema Trials (GREAT) database and trial registries up to 1 March 2023. We included randomized trials examining ≥ 8 weeks of treatment with systemic immunomodulatory medications for moderate-to-severe AD. We screened titles, abstracts and full texts and abstracted data independently, in duplicate. Outcomes included the proportion of patients achieving at least 50%, 75% and 90% improvements in Eczema Area and Severity Index (EASI 50, EASI 75 and EASI 90, respectively) and Investigator Global Assessment (IGA) success. We performed random-effects Bayesian NMAs to calculate odds ratios (OR) and 95% credible intervals (CrIs) between each intervention for each outcome. RESULTS: Eighty-three trials with 22 122 participants were included in the systematic review. In analyses limited to trials of 8-16 weeks' duration with predominantly adult populations, abrocitinib 200â mg daily (OR 1.5, 95% CrI 1.1-2.2) and upadacitinib 15â mg daily (OR 1.7, 95% CrI 0.9-3.3) and 30â mg daily (OR 2.5, 95% CrI 1.3-5.0) were associated with higher odds of achieving EASI 50 vs. dupilumab. Abrocitinib 100â mg daily (OR 0.7, 95% CrI 0.5-1.0), baricitinib 2â mg daily (OR 0.4, 95% CrI 0.3-0.5) and 4â mg daily (OR 0.5, 95% CrI 0.3-0.7), and tralokinumab (OR 0.4, 95% CrI 0.3-0.6) were associated with lower odds of achieving EASI 50 vs. dupilumab. Results were similar for EASI 75, EASI 90 and IGA success. CONCLUSIONS: Supporting results for continuous outcome measures, upadacitinib 30â mg daily and abrocitinib 200â mg daily are the most efficacious with regard to binary efficacy endpoints up to 16 weeks in adults with moderate-to-severe AD, followed by upadacitinib 15â mg daily, dupilumab and abrocitinib 100â mg daily. Dupilumab and both doses of upadacitinib and abrocitinib are more efficacious than baricitinib 4 and 2â mg daily and tralokinumab.
Assuntos
Azetidinas , Dermatite Atópica , Eczema , Purinas , Pirazóis , Pirimidinas , Sulfonamidas , Adulto , Humanos , Dermatite Atópica/tratamento farmacológico , Metanálise em Rede , Teorema de Bayes , Resultado do Tratamento , Imunoglobulina A , Índice de Gravidade de Doença , Método Duplo-CegoRESUMO
BACKGROUND: The main conventional systemic atopic dermatitis (AD) treatments are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomised controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA. OBJECTIVES: The aim of this study was to compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD. METHODS: We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). Minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression was used to compare the hazards of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits. RESULTS: 488 patients (n=311 adults and n=177 children/adolescents) on dupilumab (n=282), methotrexate (n=149), or CyA (n=57) were included. CyA and MTX were primarily used first line, while dupilumab was mainly a second line systemic as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared to MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared to MTX. In severe patients the reduction in EASI, POEM, and PP-NRS was even greater with CyA. The incidence of AEs was similar across groups (734, 654 and 594 per 10,000 person-month on CyA, dupilumab and MTX respectively). CONCLUSIONS: This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within one follow-up year.
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Various severe acute respiratory syndrome coronavirus 2 vaccines with different platforms have been administered worldwide; however, their effectiveness in critical cases of COVID-19 has remained a concern. In this national cohort study, 24 016 intensive care unit (ICU) coronavirus disease-2019 (COVID-19) admissions were included from January to April 2022. The mortality and length of ICU stay were compared between the vaccinated and unvaccinated patients. A total of 9428 (39.25%) patients were unvaccinated, and 14 588 (60.75%) patients had received at least one dose of the vaccine. Compared with the unvaccinated, the first, second, and third doses of vaccine resulted in 8%, 20%, and 33% lower risk of ICU mortality in the adjusted model, with risk ratio (RR): 0.92, 95% confidence interval (CI): 0.84-1.001, RR: 0.80, 95% CI: 0.77-0.83, and RR: 0.67, 95% CI: 0.64-0.71, respectively. The mean survival time was significantly shorter in the unvaccinated versus the fully vaccinated patients (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.88); p < 0.001). All vaccine platforms successfully decreased the hazard of ICU death compared with the unvaccinated group. The duration of ICU stay was significantly shorter in the fully vaccinated than in unvaccinated group (MD, -0.62, 95% CI: -0.82 to -0.42; p < 0.001). Since COVID-19 vaccination in all doses and platforms has been able to reduce the risk of mortality and length of ICU-stay, universal vaccination is recommended based on vaccine availability.
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COVID-19 , Vacinas , Humanos , COVID-19/prevenção & controle , Irã (Geográfico)/epidemiologia , SARS-CoV-2 , Vacinas contra COVID-19 , Estudos de Coortes , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Chronic Kidney Disease (CKD) is a prevalent and life-threatening situation recognized as an emerging health issue. The present study aimed to evaluate the effect of demographic and laboratory parameters on the survival of patients with End-Stage Renal Disease (ESRD) in a hemodialysis (HD) center in Iran. MATERIALS AND METHODS: This study was conducted on patients receiving chronic HD in Iran Helal Pharmaceutical and Clinical Complex between 2014 and 2018. The survival time was considered as the time interval between HD initiation and death. Receiving kidney transplantation was regarded as a competing risk, and an improper form of two-parameter Weibull distribution was utilized to simultaneously model the time to both death and renal transplantation. The Bayesian approach was conducted for parameters estimation. RESULTS: Overall, 29 (26.6%) patients expired, and 19 (17.4%) received kidney transplants. The male gender was related to poor survival, having nearly 4.6 folds higher hazard of mortality (90% HPD region: 1.36-15.49). Moreover, Serum calcium levels [Formula: see text]9.5 mg/dL (adjusted Sub-hazard ratio (S-HR)=2.33, 90% HPD region: 1.05-5.32) and intact parathyroid hormone (iPTH) [Formula: see text]150 pg/mL (adjusted S-HR = 2.56, 90% HPD region: 1.09-6.15) were associated with an elevated hazard of mortality. The cumulative incidence function (CIF) for transplantation was greater than death in the first two years of the study. Subsequently, the CIF for death exceeded transplantation in the following two years. The 4-year cumulative incidence of death and kidney transplantation was 63.7% and 36.3%, respectively. CONCLUSION: Male gender, hypercalcemia, and hypoparathyroidism were associated with worse outcomes. Correcting mentioned laboratory parameters may improve patients' survival in the HD population.
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Falência Renal Crônica , Transplante de Rim , Insuficiência Renal Crônica , Humanos , Masculino , Teorema de Bayes , Falência Renal Crônica/epidemiologia , Diálise RenalRESUMO
BACKGROUND: Increased arterial stiffness and pulse wave velocity (PWV) of the aorta and large arteries impose adverse hemodynamic effects on the heart and other organs. Antihypertensive treatment reduces PWV, but it is unknown whether this results from an unloading of stiffer elements in the arterial wall or is due to an alternate functional or structural change that might differ according to class of antihypertensive drug. METHODS: We performed a systematic review and meta-analysis of the effects of different antihypertensive drug classes and duration of treatment on PWV with and without adjustment for change in mean arterial blood pressure (BP; study 1) and compared this to the change in PWV after an acute change in transmural pressure, simulating an acute change in BP (study 2). RESULTS: A total of 83 studies involving 6200 subjects were identified. For all drug classes combined, the reduction of PWV was 0.65 (95% CI, 0.46-0.83) m/s per 10 mmâ Hg reduction in mean arterial BP, a change similar to that induced by an acute change in transmural pressure in a group of hypertensive subjects. When adjusted for change in mean arterial BP, the reduction in PWV after treatment with beta-blockers or diuretics was less than that after treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists or calcium channel antagonists. CONCLUSIONS: Reduction in PWV after antihypertensive treatment is largely explained by the reduction in BP, but there are some BP-independent effects. These might increase over time and contribute to better outcomes over the long term, but this remains to be demonstrated in long-term clinical trials.
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Anti-Hipertensivos , Pressão Sanguínea , Hipertensão , Análise de Onda de Pulso , Rigidez Vascular , Humanos , Análise de Onda de Pulso/métodos , Hipertensão/fisiopatologia , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Rigidez Vascular/fisiologia , Rigidez Vascular/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Pressão Sanguínea/efeitos dos fármacosRESUMO
Importance: There are multiple approved systemic treatments for atopic dermatitis. Lebrikizumab is a newly licensed biologic medication that has been compared to placebo in clinical trials but not to other systemic treatments. Objective: To compare reported measures of efficacy and safety of lebrikizumab to other systemic treatments for atopic dermatitis in a living systematic review and network meta-analysis. Data Sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Latin American and Caribbean Health Science Information database, the Global Resource of Eczema Trials database, and trial registries were searched from inception through November 3, 2023. Study Selection: Randomized clinical trials evaluating 8 or more weeks of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis. Titles, abstracts, and full texts were screened in duplicate. Data Extraction and Synthesis: Data were abstracted in duplicate and random-effects bayesian network meta-analyses were performed. Minimal important differences were used to define important differences between medications. Certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). The updated analysis was completed from December 13, 2023, to February 20, 2024. Main Outcome Measures: Efficacy outcomes were the Eczema Area and Severity Index (EASI), the Patient Oriented Eczema Measure (POEM) Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS) and were compared using mean difference (MD) with 95% credible intervals (CrI). Safety outcomes were serious adverse events and withdrawal due to adverse events. Other outcomes included the proportion of participants with 50%, 75%, and 90% improvement in EASI (EASI-50, -75, -90) and the proportion with success on the Investigator Global Assessment compared using odds ratios with 95% CrI. Results: The study sample included 98 eligible trials, with a total of 24â¯707 patients. Lebrikizumab was associated with no important difference in change in EASI (MD, -2.0; 95% CrI, -4.5 to 0.3; moderate certainty), POEM (MD, -1.1; 95% CrI -2.5 to 0.2; moderate certainty), DLQI (MD, -0.2; 95% CrI -2.1 to 1.6; moderate certainty), or PP-NRS (MD, 0.1; 95% CrI -0.4, 0.6; high certainty) compared to dupilumab among adults with atopic dermatitis who were treated for up to 16 weeks. Dupilumab was associated with higher odds of efficacy in binary outcomes compared with lebrikizumab. The relative efficacy of other approved systemic medications was similar to that found by previous updates of this living study, with high-dose upadacitinib and abrocitinib demonstrating numerically highest relative efficacy. For safety outcomes, low event rates limited useful comparisons. Conclusions and Relevance: In this living systematic review and network meta-analysis, lebrikizumab was similarly effective to dupilumab for the short-term treatment of atopic dermatitis in adults. Clinicians and patients can use these comparative data to inform treatment decisions.
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BACKGROUND: The coronavirus 2019 (COVID-19) has affected the lives of many people worldwide. Patients with chronic underlying morbidities are vulnerable to get the severe form of the infection. The goal of this study was to evaluate the outcome of patients with pulmonary arterial hypertension during the COVID-19 pandemic in Iran. METHODS: This cross-sectional study was conducted at a large tertiary center for pulmonary artery hypertension (PAH) patients. The primary end point was the prevalence of SARS-CoV-2 infection in PAH patients. The secondary end points were investigating the severity and mortality of COVID-19 infection in PAH patients during the COVID-19 pandemic. RESULTS: Totally 75 patients were enrolled in the study from December 2019 to October 2021 and 64% were female. The mean ± SD age was 49 ± 16 years. The prevalence of COVID-19 in PAH/chronic thromboembolic pulmonary hypertension patients was 44%. About 66.7% of patients had comorbidities, which was a prognostic factor for COVID-19 infection in PAH patients (P < 0.001). Fifty-six percent of infected patients were asymptomatic. The most reported symptoms in symptomatic patients were fever (28%) and malaise (29%). Twelve percent of patients were admitted with severe symptoms. The mortality rate in infected individuals was 3.7%. CONCLUSIONS: COVID-19 infection in PAH/chronic thromboembolic pulmonary hypertension patients seems to be associated with high mortality and morbidity. More scientific proof is needed to clarify different aspect of COVID-19 infection in this population.