Efficacy and Safety of Intranasal Fentanyl in Pediatric Emergencies: A Systematic Review and Meta-analysis.

BACKGROUND: Intranasal fentanyl (INF) has gained popularity in pediatric emergency departments (EDs) as an effective alternative to intravenous morphine for treating acute moderate to severe pain. Intranasal fentanyl eliminates the need for invasive access, making it advantageous for patients with minor injuries. Our study aims to provide a comprehensive evaluation of the available evidence regarding the effectiveness and safety of INF administration in pediatric emergency wards, particularly compared with other treatment options described in the literature. METHODS: A thorough search strategy identified randomized controlled trials assessing INF in the pediatric emergency ward. Eligible studies were independently screened, and relevant data were extracted. The analysis used pooled risk ratio (RR) for dichotomous outcomes and the standardized mean difference (SMD) for continuous ones. Randomized controlled trials' quality was assessed using the Cochrane Risk of Bias Assessment Tool 2. RESULTS: In our study, 8 randomized controlled trials involving 806 patients, INF demonstrated superior effectiveness in reducing pain compared with other comparators at the 15- to 20-minute mark (SMD, -0.23; 95% confidence interval, -0.37 to -0.08; P = 0.002). However, no significant differences were found at the 30- and 60-minute time points (SMDs, -0.16; 95% CI, -0.50, 0.19; P = 0.37; and -0.16; 95% CI, -0.50 to 0.19; P = 0.78) except when excluding one study to resolve heterogeneity at the 30-minute mark (RR, -0.02; 95% CI, -0.24 to 0.20; P = 0.87). Intranasal fentanyl also exhibited a better adverse outcome profile, with a lower risk of total adverse events and nausea/vomiting (RR, 0.66; 95% CI, 0.48-0.91; P = 0.01; and RR, 0.43; 95% CI, 0.30-0.63; P > 0.001) compared with other analgesics. However, no significant differences were observed for dizziness and hallucination (RR, 0.43; 95% CI, 0.30-0.63; P = 0.68; and RR, 0.43; 95% CI, 0.30-0.63; P = 0.35). CONCLUSIONS: Our study assessed the effectiveness of INF compared with other analgesics in pain reduction. Intranasal fentanyl demonstrated superior pain reduction at the 15- to 20-minute point but showed no significant differences at 30 and 60 minutes. Intranasal fentanyl also had a more favorable adverse event profile, with a lower risk of nausea and vomiting than other analgesics. However, no significant differences were observed in dizziness and hallucination between the groups.

Safety and efficacy of edaravone in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.

AIM: The study aims to increase understanding of edaravone's efficacy and safety as an amyotrophic lateral sclerosis (ALS) treatment and provide significant insights regarding this field's future research. METHODS: We conducted a comprehensive search of the Embase, PubMed, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials and observational studies up until September 2022. We evaluated the studies' quality using the Cochrane risk of bias tool and the National Institutes of Health tool. RESULTS: We included 11 studies with 2845 ALS patients. We found that edaravone improved the survival rate at 18, 24, and 30 months (risk ratio (RR) = 1.03, 95% confidence interval (CI) [1.02 to 1.24], P = 0.02), (RR = 1.22, 95% CI [1.06 to 1.41], P = 0.007), and (RR = 1.17, 95% CI [1.01 to 1.34], P = 0.03), respectively. However, the administration of edaravone did not result in any significant difference in adverse effects or efficacy outcomes between the two groups, as indicated by a P value greater than 0.05. CONCLUSION: Edaravone improves survival rates of ALS patients at 18, 24, and 30 months with no adverse effects. However, edaravone does not affect functional outcomes. In order to ensure the validity of our findings and assess the results in accordance with the disease stage, it is essential to carry out additional prospective, rigorous, and high-quality clinical trials. The current study offers preliminary indications regarding the effectiveness and safety of edaravone. However, further comprehensive research is required to establish the generalizability and sustainability of the findings.

Inhaled corticosteroids' effect on COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

Background: More than six million people died due to COVID-19, and 10-15% of infected individuals suffer from post-covid syndrome. Corticosteroids are widely used in the management of severe COVID-19 and post-acute COVID-19 symptoms. This study synthesizes current evidence of the effectiveness of inhaled corticosteroids (ICS) on mortality, hospital length-of-stay (LOS), and improvement of smell scores in patients with COVID-19. Methods: We searched Embase, Web of Science, PubMed, Cochrane Library, and Scopus until Aug 2022. The Cochrane risk of bias tool was used to assess the quality of studies. We evaluated the effectiveness of ICS in COVID-19 patients through measures of mortality, LOS, alleviation of post-acute COVID-19 symptoms, time to sustained self-reported cure, and sense of smell (visual analog scale (VAS)). Results: Ten studies were included in the meta-analysis. Our study showed a significant decrease in the LOS in ICS patients over placebo (MD = -1.52, 95% CI [-2.77 to -0.28], p-value = 0.02). Patients treated with intranasal corticosteroids (INC) showed a significant improvement in VAS smell scores from week three to week four (MD =1.52, 95% CI [0.27 to 2.78], p-value = 0.02), and alleviation of COVID-related symptoms after 14 days (RR = 1.17, 95% CI [1.09 to 1.26], p-value < 0.0001). No significant differences were detected in mortality (RR= 0.69, 95% CI [0.36 to 1.35], p-value = 0.28) and time to sustained self-reported cure (MD = -1.28, 95% CI [-6.77 to 4.20], p-value = 0.65). Conclusion: We concluded that the use of ICS decreased patient LOS and improved COVID-19-related symptoms. INC may have a role in improving the smell score. Therefore, using INC and ICS for two weeks or more may prove beneficial. Current data do not demonstrate an effect on mortality or time to sustained self-reported cure. However, the evidence is inconclusive, and more studies are needed for more precise data.

Antithrombotic Strategies After Transcatheter Aortic Valve Replacement in Patients Without an Indication of Oral Anticoagulants: A Network Meta-Analysis of Randomized Controlled Trials.

Single-antiplatelet therapy (SAPT) has been a standard of care posttranscatheter aortic valve replacement with no clear evidence exist using direct oral anticoagulants (DOACs), vitamin K antagonists (VKA), or dual antiplatelet agents (DAPT); thus we aim to compare the safety and efficacy of the various antithrombotic strategies after transcatheter aortic valve replacement. We performed a network meta-analysis using a frequentist framework, pooling dichotomous outcomes using risk ratio (RR), and continuous data using mean difference, along with the corresponding 95% confidence interval (CI). Nine randomized controlled trials with 4193 patients were included, 567 patients were in the VKA group, 591 patients in the SAPT group, 1571 patients in the DAPT group, and 1464 patients in the DOACs group. Only DOAC showed a statistically significant higher risk of all-cause mortality [RR of 1.88 (95% CI: 1.07-3.28)] with no statistically significant difference between our arms in terms of mortality. For minor bleeding, DAPT had a significant higher risk with RR of 1.53 (95% CI: 1.04-2.25), while for major bleeding, DAPT and DOAC had a significant higher risk with RR of 2.36 (95% CI: 1.27-4.40) and 4.74 (95% CI: 2.05-10.92), respectively. There was no significant difference in terms of stroke and life-threatening bleeding. Moreover, only DOAC showed a significantly lower risk for valve thrombosis, when compared to other strategies [RR: 0.24 (95% CI: 0.13-0.46)]. Overall, SAPT had lower major bleeding events compared to other arms. There were no differences in the outcomes of stroke, myocardial infarction, or life-threatening bleeding outcomes. However, DOACs significantly reduced valve thrombosis compared to VKAs.

Risk factors of diabetes and cancer-specific mortalities in patients with infiltrating ductal carcinoma of the breast: a population-based study.

BACKGROUND AND AIMS: Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast. MATERIALS AND METHODS: Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software. RESULTS: A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV. CONCLUSION: In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.

A Systematic Review and Network Meta-Analysis of the Outcomes of Patients With Total Knee Arthroplasty Using Cemented, Uncemented, or Hybrid Techniques.

In this study, we aim to explore the differences among the three types of fixation methods for the components of the knee joint in patients who underwent total knee arthroplasty (TKA). These methods are cemented, uncemented, and hybrid fixation. Cemented fixation means that a special type of grout is used to attach the components to the bone. Uncemented fixation means that the components are designed to fit tightly into the bone and allow new bone growth to secure them. Hybrid fixation means that a combination of cemented and uncemented fixation is used for different components. We searched four online databases to find studies relevant to our research question. We use the R program (R Foundation for Statistical Computing, Vienna, Austria) for network meta-analysis (NMA) to analyze the data from the studies. We calculate the mean difference (MD) and the 95% confidence interval (CI) for each outcome, which are statistical measures of the difference and the uncertainty between methods. We use these measures for continuous outcomes, meaning they can have any value. For dichotomous outcomes, meaning they can only have two values, we use the risk ratio (RR) and the 95% CI, which are statistical measures of the relative risk and the uncertainty between methods. We assess the quality of randomized controlled trials, which are studies that randomly assign participants to different methods, using the Cochrane Risk of Bias Assessment Tool 1, a tool that evaluates the potential biases in the studies. We include 21 studies, and our analysis shows that cemented TKA reveals a statistically significant decrease in pain with hybrid TKA (MD = -2.82). That said, we find no significant differences between uncemented and cemented or hybrid (MD = -0.80 and -2.02, respectively). The results show that there is no significant difference between uncemented TKA and cemented TKA or hybrid technique (RR = 0.87, 95% CI 0.35-2.14; RR = 0.73, 95% CI 0.22-2.39, respectively). Also, we find no significant difference between cemented TKA and hybrid TKA (RR = 0.84, 95% CI 0.24-2.93). Cemented TKA is associated with a lower risk of deep vein thrombosis (DVT) incidence rate. Moreover, it shows a significant decrease in pain compared to hybrid TKA. Future research is needed to compare among the three interventions.

Safety and efficacy of total ankle arthroplasty versus ankle arthrodesis for ankle osteoarthritis: A systematic review and meta-analysis.

Osteoarthritis is the most common joint disease-causing pain and disability, and its management keeps creating a debate. So, we aimed to compare the safety and efficacy of total ankle arthroplasty and ankle arthrodesis for ankle osteoarthritis. We searched PubMed, Cochrane, Scopus, and Web of Science till August 2021. The outcomes were pooled as Mean difference (MD) or Risk Ratio (RR), and 95% confidence interval. We included 36 studies. The results showed a significantly lower risk of infections in total ankle arthroplasty (TAA) than ankle arthrodesis (AA) (RR= 0.63, 95% CI [0.57, 0.70], p < 0.00001), amputations (RR= 0.40, 95% CI [0.22, 0.72], p = 0.002), postoperative non-union (RR= 0.11, 95% CI [0.03, 0.34], p = 0.0002), and a significant increase of overall range of motion in TAA than AA. Our results preferred total ankle arthroplasty over ankle arthrodesis in terms of lowering the rates of infections, amputations, and postoperative non-union, with better change in the overall range of motion.

Efficacy and Safety of Therapeutic Hypothermia as an Adjuvant Therapy for Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.

The study aims to compare the use of hypothermia in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) with control. We systematically searched four electronic databases until March 2022. The inclusion criteria were any study design that compared hypothermia in patients with MI undergoing PCI with control. The risk of bias assessment of the included randomized controlled trials was conducted through Cochrane Tool, while the quality of the included cohort studies was assessed by the NIH tool. The meta-analysis was performed on RevMan. A total of 19 studies were entered. Regarding the mortality, there were nonsignificant differences between hypothermia and control (odds ratio [OR] = 1.06, 95% confidence interval [CI] 0.75 to 1.50, p = 0.73). There was also no significant difference between the control and hypothermia in recurrent MI (OR = 1.21, 95% CI 0.64 to 2.30, p = 0.56). On the other hand, the analysis showed a significant favor for hypothermia over the control infarct size (mean difference = -1.76, 95% CI -3.04 to -0.47, p = 0.007), but a significant favor for the control over hypothermia in the overall bleeding complications (OR = 1.88, 95% CI 1.11 to 3.18, p = 0.02). Compared with the control, hypothermia reduced the infarct size of the heart, but this finding was not consistent across studies. However, the control had lower rates of bleeding problems. The other outcomes, such as death and the incidence of recurrent MI, were similar between the two groups.

Hospital and laboratory outcomes of patients with COVID-19 who received vitamin D supplementation: a systematic review and meta-analysis of randomized controlled trials.

Coronavirus disease 2019 (COVID-19) has a wide-ranging spectrum of clinical symptoms, from asymptomatic/mild to severe. Recent research indicates that, among several factors, a low vitamin D level is a modifiable risk factor for COVID-19 patients. This study aims to evaluate the effect of vitamin D on hospital and laboratory outcomes of patients with COVID-19.Five databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) and clinicaltrials.gov were searched until July 2022, using relevant keywords/Mesh terms. Only randomized clinical trials (RCTs) that addressed the topic were included. The Cochrane tool was used to assess the studies' risk of bias, and the data were analyzed using the review manager (RevMan 5.4).We included nine RCTs with 1586 confirmed COVID-19 patients. Vitamin D group showed a significant reduction of intensive care unit (ICU) admission (risk ratio = 0.59, 95% confidence interval (CI) [0.41, 0.84], P = 0.003), and higher change in vitamin D level (standardized mean difference = 2.27, 95% CI [2.08, 2.47], P < 0.00001) compared to the control group. Other studied hospital and laboratory outcomes showed non-significant difference between vitamin D and the control group (P ≥ 0.05).In conclusion, vitamin D reduced the risk of ICU admission and showed superiority in changing vitamin D level compared to the control group. However, other outcomes showed no difference between the two groups. More RCTs are needed to confirm these results.