Due to the unmet needs in the management of migraine, a primary headache, and disabling disorder, the past decade has focused on developing monoclonal antibodies (mAbs) against the calcitonin-gene-related peptide (CGRP) as migraine prophylactic agents. The objective of the study was to evaluate the efficacy and safety of various anti-CGRP mAbs in the prevention of chronic migraine. Network meta-analysis (NMA) was performed using the Bayesian framework to estimate the efficacy and safety of mAbs after performing a literature search in PubMed, MEDLINE, Cochrane database, and International Clinical Trial Registry Platform (ICTRP). The outcomes calculated were in terms of mean difference (MD) or odds ratio (OR) with a 95% credible interval (95%CrI). Network graphs were constructed and node-split analysis was done to analyze the inconsistency. The NMA included a total of 10 clinical trials.Galacanezumab (120 mg) (MD: −2.7; 95%CrI: −4.8 to −0.83) was found to be better than other mAbs in terms of the difference in mean migraine days (MMD). Fremanezumab quarterly dose administration showed the best response (OR: 2.9; 95%CrI: 1.9 to 4.6) in terms of responder rate. Eptinezumab was found to be safer (OR: 0.88; 95%CrI: 0.61− 1.3) as compared to other mAbs in terms of the rate of adverse events. Fremanezumab (quarterly) ranked better in terms of response rate, and eptinezumab was found to be the safest in the prophylactic management of migraine.Galacenequmab was better at reducing MMD. Further studies are needed to evaluate the long-term safety, efficacy, and use of mAbs in migraine patients.

Clozapine is the only approved drug for treatment-resistant schizophrenia, but the response to the drug is often inadequate. Augmentation with other antipsychotics, anticonvulsants, and antidepressants is recommended for such patients, but there is a lack of evidence regarding the most effective therapy. This network meta-analysis was conducted to evaluate the efficacy of pharmacological agents used in the augmentation strategies in patients who were partialon-responders to clozapine. Relevant data were extracted from 30 randomized controlled trials through searches of electronic databases (MEDLINE/PubMed, Embase, Cochrane, clinical trial registries). PRISMA guidelines were followed for the extraction, management, analysis, and reporting of the data. The outcome measure in this study was a reduction in symptom severity according to total PANSS/BPRS and was reported as the standardized mean difference with a 95% credible interval. Bayesian network meta-analysis with random effects model and uninformative priors was conducted, and the ranking probability of each intervention was done. Meta-regression was done to assess the effect of duration on the reduction in symptom severity scores. Mirtazapine (−5.2 [95%CrI: −7.7, −2.7]) and memantine (−2.1 [95%CrI: −4.0, −0.19]) were more efficacious than placebo for augmentation of clozapine in partialon-responders and were the most effective adjunctive agents as per SUCRA scores. Both drugs did not cause a significant increase in frequency of adverse events compared to placebo. There was a significant effect of duration on the reduction in symptom severity. There was no evident publication bias. Mirtazapine and memantine may prove beneficial for augmentation of clozapine in non/partial responders to monotherapy.

Background: Dexmedetomidine, an alpha-2 agonist, has been used for attenuation of hemodynamic response to laryngoscopy but not through the nebulized route. We evaluated the effects of preoperative dexmedetomidine nebulization on the hemodynamic response to laryngoscopy and intubation and examined the intraoperative anesthetic-analgesic requirements and recovery outcomes. Methods: Overall, 120 ASA I & II adult patients (of either gender) undergoing elective surgeries and requiring tracheal intubation, were randomized to receive nebulized dexmedetomidine (1 µg/kg in 3–4 ml of 0.9% saline) or 0.9% saline (3–4 ml), 30 min before anesthesia induction. Heart rate and non-invasive systolic blood pressure were monitored for 10 min following laryngoscopy. Results: After laryngoscopy, linear mixed effect modelling showed significantly lower trend of increase in heart rate in the dexmedetomidine group versus saline (P = 0.012); however, there was no difference in the systolic blood pressure changes between the two groups (P= 0.904). Induction dose of propofol (P < 0.001), intraoperative fentanyl consumption (P = 0.007), and isoflurane requirements (P = 0.013) were significantly lower in the dexmedetomidine group. There was no difference in the 2-h incidence of postoperative nausea and vomiting (PONV) (P = 0.612) or sore-throat (P = 0.741). Conclusions Nebulized dexmedetomidine at 1 µg/kg attenuated the increase in heart rate but not systolic blood pressure following laryngoscopy and reduced the intraoperative anesthetic and analgesic consumption. There was no effect on early PONV, sore-throat, or increase in incidence of adverse effects. Nebulized dexmedetomidine may represent a favorable alternative to the intravenous route in short duration surgeries.

Background: Subanesthetic intravenous (IV) ketamine acts as an analgesic and has opioid-sparing effects, particularly for acute postoperative pain; however, its effectiveness in children is understudied. The primary aim of this study was to evaluate the non-inferiority of subanesthetic IV ketamine vs. caudal bupivacaine for postoperative analgesia in children undergoing infraumbilical surgery. Methods: Children aged < 6 years were enrolled in this single-blind study and randomized to receive either subanesthetic IV ketamine (0.3 mg/kg) or caudal 0.125% bupivacaine (1 ml/kg) along with general anesthesia. Postoperative pain was assessed using the FLACC scale at 30 minutes and 1, 2, 3, and 6 h post-operation. Intra- and postoperative opioid consumption, time to extubation, postoperative vomiting, agitation, sedation, and inflammatory markers were also assessed. Results: Altogether, 141 children completed the study (ketamine group: n = 71, caudal group: n = 70) The cumulative proportion of children without significant postoperative pain (FLACC score < 4) in the first 6 h post-surgery was 45.1% in the ketamine group vs. 72.9% in the caudal group (P < 0.001). More children in the ketamine group required an additional dose of intraoperative fentanyl (33.8% vs. 5.7%, P < 0.001) and postoperative tramadol (54.9% vs. 27.1%, P < 0.001). However, postoperative agitation, sedation, and other secondary outcomes were similar between the groups. Conclusions Subanesthetic ketamine is inferior to caudal bupivacaine for postoperative analgesia in children aged < 6 years undergoing infra-umbilical surgeries; however, other postoperative outcomes are similar.

Background: Dexmedetomidine, an alpha-2 agonist, has been used for attenuation of hemodynamic response to laryngoscopy but not through the nebulized route. We evaluated the effects of preoperative dexmedetomidine nebulization on the hemodynamic response to laryngoscopy and intubation and examined the intraoperative anesthetic-analgesic requirements and recovery outcomes. Methods: Overall, 120 ASA I & II adult patients (of either gender) undergoing elective surgeries and requiring tracheal intubation, were randomized to receive nebulized dexmedetomidine (1 µg/kg in 3–4 ml of 0.9% saline) or 0.9% saline (3–4 ml), 30 min before anesthesia induction. Heart rate and non-invasive systolic blood pressure were monitored for 10 min following laryngoscopy. Results: After laryngoscopy, linear mixed effect modelling showed significantly lower trend of increase in heart rate in the dexmedetomidine group versus saline (P = 0.012); however, there was no difference in the systolic blood pressure changes between the two groups (P= 0.904). Induction dose of propofol (P < 0.001), intraoperative fentanyl consumption (P = 0.007), and isoflurane requirements (P = 0.013) were significantly lower in the dexmedetomidine group. There was no difference in the 2-h incidence of postoperative nausea and vomiting (PONV) (P = 0.612) or sore-throat (P = 0.741). Conclusions Nebulized dexmedetomidine at 1 µg/kg attenuated the increase in heart rate but not systolic blood pressure following laryngoscopy and reduced the intraoperative anesthetic and analgesic consumption. There was no effect on early PONV, sore-throat, or increase in incidence of adverse effects. Nebulized dexmedetomidine may represent a favorable alternative to the intravenous route in short duration surgeries.

BACKGROUND: AND PURPOSE: The role of low-frequency repetitive transcranial stimulation (rTMS) in drug-resistant epilepsy (DRE) has been conflicting and inconclusive in previous clinical trials. This meta-analysis evaluated the efficacy of rTMS on seizure frequency and epileptiform discharges in DRE. METHODS: A standard meta-analysis protocol was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO: CRD42018088544). After performing a comprehensive literature search using specific keywords in MEDLINE, the Cochrane database, and the International Clinical Trial Registry Platform (ICTRP), reviewers assessed the eligibility and extracted data from seven relevant clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. A random-effects model was used to estimate the effect size as the mean difference in seizure frequency and interictal epileptiform discharges between the groups. Quality assessment was performed using a risk-of-bias assessment tool, and a meta-regression was used to identify the variables that probably influenced the effect size. RESULTS: The random-effects model analysis revealed a pooled effect size of −5.96 (95% CI= −8.98 to −2.94), significantly favoring rTMS stimulation (p=0.0001) over the control group with regard to seizure frequency. The overall effect size for interictal epileptiform discharges also significantly favored rTMS stimulation (p < 0.0001), with an overall effect size of −9.36 (95% CI=−13.24 to −5.47). In the meta-regression, the seizure frequency worsened by 2.00±0.98 (mean±SD, p=0.042) for each week-long lengthening of the posttreatment follow-up period, suggesting that rTMS exerts only a short-term effect. CONCLUSIONS This meta-analysis shows that rTMS exerts a significant beneficial effect on DRE by reducing both the seizure frequency and interictal epileptiform discharges. However, the meta-regression revealed only an ephemeral effect of rTMS.

PURPOSE: Hip fractures among elderly patients are surgical emergencies. During COVID-19 pandemic time, many such patients could not be operated at early time because of the limitation of the medical resources, the risk of infection and redirection of medical attention to a severe infective health problem. METHODS: A search of electronic databases (PubMed, Medline, CINAHL, EMBASE and the Cochrane Central Register of Controlled Trials) with the keywords "COVID", "COVID-19″, "SARS-COV-2", "Corona", "pandemic", "hip fracture", "trochanteric fracture" and "neck femur fracture" revealed 64 studies evaluating treatment of hip fracture in elderly patients during COVID-19 pandemic time. The 30-day mortality rate, inpatient mortality rate, critical care/special care need, readmission rate and complications rate in both groups were evaluated. Data were analyzed using Review Manager (RevMan) V.5.3. RESULTS: After screening, 7 studies were identified that described the mortality and morbidity in hip fractures in both COVID-19 infected (COVID-19 +) and non-infected (COVID-19 -) patients. There were significantly increased risks of 30-day mortality (32.23% COVID-19 + death vs. 8.85% COVID-19 - death) and inpatient mortality (29.33% vs. 2.62%) among COVID-19 + patients with odds ratio (OR) of 4.84 (95% CI: 3.13 - 7.47, p < 0.001) and 15.12 (95% CI: 6.12 - 37.37, p < 0.001), respectively. The COVID-19 + patients needed more critical care admission (OR = 5.08, 95% CI: 1.49 - 17.30, p < 0.009) and they remain admitted for a longer time in hospital (mean difference = 3.6, 95% CI: 1.74 - 5.45, p < 0.001); but there was no difference in readmission rate between these 2 groups. The risks of overall complications (OR = 17.22), development of pneumonia (OR = 22.25), and acute respiratory distress syndrome/acute respiratory failure (OR = 32.96) were significantly high among COVID-19 + patients compared to COVID-19 - patients. CONCLUSIONS There are increased risks of the 30-day mortality, inpatient mortality and critical care admission among hip fracture patients who are COVID-19 +. The chances of developing pneumonia and acute respiratory failure are more in COVID-19 + patients than in COVID-19 ‒ patients.
Humans ; Aged ; COVID-19/epidemiology* ; Pandemics ; Hospital Mortality ; Hip Fractures/surgery* ; Pneumonia ; Morbidity ; Respiratory Insufficiency/complications*