Efficacy and safety of tenecteplase in comparison to alteplase in acute ischemic stroke: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Alteplase is the standard medical therapy for acute ischemic stroke (AIS) patients who present within 4.5 h of symptom onset. Tenecteplase is a modified alteplase variant with pharmacological and practical advantages over alteplase. Many trials have investigated the efficacy and safety of tenecteplase against alteplase. This systematic review and meta-analysis aimed to compare the efficacy and safety of tenecteplase to alteplase across randomized controlled trials. METHOD: Medline, Embase, and Cochrane CENTRAL were used to search the related articles until February 20, 2023. Randomized controlled trials (RCTs) that compared the effectiveness and safety of tenecteplase against alteplase for AIS patients were included. Screening, risk of bias assessment, and data extraction were performed following PRISMA guidelines. Data were pooled using a random-effect model. RESULTS: Ten RCTs were included, with a total of 5123 patients. There was no significant difference between the two interventions in modified rankin scale 0-1 (mRS 0-1) (RR= 1.04, 95% CI [0.99-1.10], P = 0.11, I2 =0%) and early neurological improvement (RR= 1.06, 95% CI [0.97-1.15], P = 0.21, I2 =35). There was no difference in the rates of symptomatic intracranial hemorrhage (RR= 1.18, 95% CI [0.84-1.65], P = 0.35, I2 = 0%). Tenecteplase was associated with significantly higher complete recanalization rate compared to alteplase (RR= 1.17, 95% CI [1.00-1.36], P = 0.05, I2 =0%). For large vessel occlusion (LVO) patients assigned to tenecteplase, there was a significant improvement in mRS 0-1 (RR= 1.28, 95% CI [1.07-1.52], P = 0.006, I2 =0%). CONCLUSION: Based on our meta-analysis, tenecteplase has similar efficacy and safety to alteplase, with a more promising effect in patients with LVO.

The efficacy and safety of varenicline nasal spray for the management of dry eye signs: a systematic review and meta-analysis.

BACKGROUND: Dry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging evidence that nicotinic acetylcholine receptor (nAChR) agonists (e.g., varenicline and simpinicline) nasal sprays are effective for DED. Our systematic review and meta-analysis assessed the efficacy and safety of varenicline nasal spray (VNS) for DED treatment. METHODS: The Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Only randomized controlled trials (RCTs) that evaluated the efficacy of VNS versus placebo were included. The efficacy endpoint was the mean change in the anesthetized Schirmer test score (STS), a measure of basal tear production, from baseline. The safety endpoints were serious adverse events (SAEs) and adverse events (AEs). The standardized mean difference (SMD) was used for continuous outcomes, while the risk ratio (RR) was used to demonstrate dichotomous variables. The certainty of the evidence was rated utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The risk of bias assessment was conducted using the Revised Cochrane risk of bias tool for randomized trials. RESULTS: Three RCTs (n = 1063) met the eligibility criteria. All RCTs had a low risk of bias. The meta-analysis found a statistically significant increase in the mean STS change from baseline on day 28. The pooled analysis found no significant difference between VNS and placebo in the frequency of SAEs and ocular AEs. However, VNS had a significant effect on developing nasal cavity-related AEs. CONCLUSION: VNS caused a highly significant improvement regarding the efficacy endpoint but caused an increased frequency of some nasal cavity-related AEs (i.e., cough and throat irritation). However, it caused neither SAEs nor ocular AEs. Included studies had a low risk of bias.

The Efficacy and Safety of Subcutaneous Ixekizumab for the Treatment of Axial Spondylarthritis: A Systematic Review and Meta-Analysis.

Axial spondylarthritis (axSpA) is a progressive inflammatory condition that is treated with various management options. Interleukin-17A (IL-17A) inhibitors are a novel therapeutic option that demonstrates both efficacy and safety. This systematic review and meta-analysis evaluated the effectiveness of ixekizumab and its safety compared to a placebo. Medline, ScienceDirect, EBSCO, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched. We included randomized control trials (RCTs) that assessed the efficacy and safety of ixekizumab versus the placebo. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) assessment was utilized to evaluate the certainty of evidence. The revised Cochrane risk of bias tool for randomized trials was used to assess the risk of bias. Four RCTs (n=1016) met the eligibility criteria. All included studies had a low risk of bias. Significant improvements in the Assessment of Spondylarthritis International Society response for 40% improvement (ASAS40) (RR = 2.39, 95% CI 1.72-3.31, P < 0.01, I2 = 23%), Ankylosing Spondylitis Disease Activity Score (ASDAS) (SMD= -9.28 95% CI -12.31- (-6.25), P < 0.01, I2=97%), and Spondylarthritis Research Consortium of Canada (SPRACC score) (SMD= -5.82 95% CI -7.16- (-4.47), P < 0.01, I2=94%) were noted in comparison to placebo. Regarding safety, there was an insignificant increase in risk for serious adverse events (SAEs) (RR = 1.19, 95% CI 0.45-3.14, P = 0.73, I2 = 0%). Additionally, significant nonserious adverse events (NSAEs) (RR = 1.54, 95% CI 1.19-1.99, P = 0.001, I2 = 0%) were noted for the ixekizumab arm. No mortality events were detected in both arms. Ixekizumab, which demonstrates significant improvement in all efficacy endpoints, is a promising management option for axSpA patients who fail non-steroidal anti-inflammatory drugs (NSAIDs) therapy. However, the significant risk of developing adverse events hinders its utilization. More high-quality RCTs with larger sample sizes and prolonged follow-up periods are warranted to further assess this treatment option.

Association Between Vitamin D, Zinc, and Thyroid Biomarker Levels With Vitiligo Disease: A Retrospective Cohort Study in a Tertiary Care Center.

Objectives Vitiligo is a dermatological autoimmune disease that has been linked with numerous risk factors. There is an elevated level of evidence suggesting a linkage between vitiligo disease and zinc, vitamin D (Vit-D), thyroid hormones, and thyroid antibody levels. Methods This retrospective cohort study included patients of all age groups of both sexes. Patients were investigated for demographics, vitiligo characteristics, and laboratory tests, including zinc, Vit-D, T3 (triiodothyronine), T4 (thyroxine), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb). Results Two hundred and ninety-seven patients were retrospectively assessed; they averaged 29 years for segmental vitiligo (SV) and 31 years for nonsegmental vitiligo (NSV). Gender-wise, our study included more females (57.5%) than males (42.5%). Females comprised approximately 51.8% of NSV patients, while males constituted 36.7%. Patients' T3, T4, and TPOAb levels correlated significantly with age (p=0.001, p <0.01, p=0.14), and elevated BMI recorded high TPOAb levels (p<0.001). An increase in TGAb was associated with extensive involvement in the depigmentation of body surface area (BSA). The segmental type had the lowest TGAb and TPOAb titers. The universal subtype of vitiligo recorded the highest TSH, T3, and TGAb levels. However, differences in laboratory test levels were insignificant for the sex, the type of vitiligo, or the subtype of vitiligo. Conclusion In conclusion, neither Vit-D nor zinc had a significant linkage with any of vitiligo's characteristics or treatments. Nonetheless, TGAb had a significant correlation to the BSA involved with vitiligo while T4 and TPOAb had a significant association with age, BMI, and BSA overall. Statistically, T3 was linked with age and BSA overall only. More studies with a higher level of evidence are required to establish the association of Vit-D, zinc, thyroid biomarkers, and thyroid antibodies.

The efficacy and safety of lebrikizumab monotherapy for the management of moderate-to-severe atopic dermatitis: A systematic review and meta-analysis.

Background: Atopic dermatitis (AD) is a chronically relapsing disease. Few biologics are approved for moderate-to-severe AD, and novel interventions are emerging. We aimed to evaluate the safety and efficacy of lebrikizumab, an IL-13 immunomodulator, as monotherapy vs. placebo in treating moderate-to-severe AD. Methods: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, and ClinicalTrials.gov registry (CT.gov) databases were systematically searched. We evaluated lebrikizumab vs. placebo and measured efficacy using Eczema Area and Severity Index (EASI), Body Surface Area (BSA), and Investigator's Global Assessment (IGA) change from baseline to week 16. Safety was evaluated by the incidence of serious adverse events (SAEs), non-serious adverse events (NSAEs), and mortality. The risk of bias was investigated using the Revised Cochrane risk of bias tool. Results: Three RCTs (n = 1,149) included 543 (47.25%) men vs. 606 (52.75%) women. Meta-analysis showed statistically significant improvement in EASI, IGA, and BSA. EASI75 at week 16 for all regimens was (RR = 2.62, 95% CI [2.06, 3.34], p < 0.00001) with the first regimen (500 mg loading dose then 200 mg every 2 weeks) showing the most significant improvement (RR = 3.02, 95% CI [2.39, 3.82], p < 0.00001). The pooled analysis of safety outcomes concluded that lebrikizumab did not correlate significantly with the incidence of SAEs, NSAEs, and mortality. Conclusion: Overall, lebrikizumab showed a significant improvement in all efficacy outcomes. Additionally, it did not contribute to any significant incidence of SAEs, NSAEs, or mortality. The risk of bias in included RCTs was minor except in the randomization domain. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment of the outcomes ranged from low to high, but predominantly high certainty of evidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022362438.

Electronic cigarettes consumption and associated factors among general population in Western Saudi Arabia.

BACKGROUND: In recent years, consumption of E-cigarettes has increased dramatically. Several studies have focused on the prevalence of E-cigarettes among specific groups of people, using it as a substitute to traditional cigarettes, or the participant knowledge regarding risks. This research was aimed on E-cigarettes' prevalence and its association to several factors in the general population of Western Saudi Arabia. DESIGN AND METHODS: Using an observational cross-sectional study, data were collected from (n=465) above 18 years old smokers during the survey at public attractions. A validated self-administered questionnaire acquired from previous studies was employed to insure the suitability for the general population of Jeddah Saudi Arabia. Sample size was calculated via Raosoft@ and adults of either gender were included in the study. Descriptive or inferential statistical analysis was performed using SPSS. RESULTS: The preponderance of e-cigarette smokers used entertainment as the reason for smoking, with an average of (33.9%). Although one reason for e-cigarette consumption was to cease traditional smoking, results showed an average of (49.4%), which is the majority of those who attempted to cease traditional smoking via e-cigarette, did not succeed in quitting traditional smoking. This study also demonstrated that participant that believed that e-cigarette is beneficial had a higher chance to cease conventional smoking than who did not (32.1% versus 14.6%) which is significant (p<0.001). CONCLUSIONS: In conclusion, this study estimated the prevalence of e-cigarette consumption among the population of Jeddah, Saudi Arabia along with assessment of elements which help increase the overall e-cigarette consumption in Jeddah.