A Systematic Review and Meta-Analysis of Prevalence, Characteristics, and Impact of Mitral Annular Calcification on Outcomes After Transcatheter Aortic Valve Implantation.

There is a paucity of data on the prognostic impact of mitral annular calcification (MAC) in patients who underwent transcatheter aortic valve implantation (TAVI) with conflicting results being reported by the studies that are published. Therefore, we performed a meta-analysis to assess the short-term and long-term outcomes of MAC in patients after TAVI. Of 25,407 studies identified after the initial database search, 4 observational studies comprising 2,620 patients (2,030 patients in the nonsevere MAC arm and 590 patients in the severe MAC arm) were included in the final analysis. Compared with patients with nonsevere MAC, the severe MAC group was associated with significantly higher incidences of overall bleeding (0.75 [0.57 to 0.98], p = 0.03, I2 = 0%) at 30 days. However, no significant difference was observed between the 2 groups for the rest of the 30-day outcomes: all-cause mortality (0.79 [0.42 to 1.48], p = 0.46, I2 = 9%), myocardial infarction (1.62 [0.37 to 7.04], p = 0.52, I2 = 0%), cerebrovascular accident or stroke (1.22 [0.53 to 2.83], p = 0.64, I2 = 0%), acute kidney injury (1.48 [0.64 to 3.42], p = 0.35, I2 = 0%), and pacemaker implantation (0.70 [0.39 to 1.25], p = 0.23, I2 = 68%). Similarly, follow-up outcomes also showed no significant difference between the 2 groups: all-cause mortality (0.69 [0.46 to 1.03], p = 0.07, I2 = 44%), cardiovascular mortality (0.52 [0.24 to 1.13], p = 0.10, I2 = 70%) and stroke (0.83 [0.41 to 1.69], p = 0.61, I2 = 22%). The sensitivity analysis, however, demonstrated significant results for all-cause mortality (0.57 [0.39 to 0.84], p = 0.005, I2 = 7%) by removing the study by Okuno et al5 and cardiovascular mortality (0.41 [0.21 to 0.82], p = 0.01, I2 = 66%) by removing the study by Lak et al.7 In conclusion, our meta-analysis corroborates the notion that isolated MAC is not an independent predictor of long-term mortality after TAVI and determines severe MAC to be a predictor of mortality at follow-up because of the higher incidence of mitral valve dysfunction associated with it.

Use of Tocilizumab in COVID-19: A Systematic Review and Meta-Analysis of Current Evidence.

Background and objectives A flare-up in coronavirus disease 2019 (COVID-19) cases threatens the health of people, and though there is no proven pharmacological treatment, many analytical studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of severe COVID-19 and that the anti-IL-6 biologic agent tocilizumab may be beneficial. This is a critical review of studies aiming to assess the safety and efficacy of tocilizumab as compared to the standard regimen in patients with COVID-19. Materials and methods Online databases (PubMed and Cochrane) were searched until June 29, 2020, for original articles investigating the immunological response in COVID-19 and its treatment with tocilizumab. Data on multiple baseline characteristics and pre-specified endpoints were extracted and pooled using a random effect model. We used Review Manager version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014, Denmark) and Stata 11.0 (Stata Corporation LP, College Station, TX) for all analyses. Risk ratios (RR) and the weighted mean difference (WMD) with the corresponding 95% confidence interval (CI) were calculated. Results From a total of 1,246 identified articles, 13 studies were included after duplicate removal and narrowing based on title and abstract. Of the 13 included studies, seven case-control studies were shortlisted for meta-analysis (quantitative) and six-single arm studies were used in the discussion (qualitative). These studies had 766 patients (351 in the tocilizumab arm and 414 in the control arm). Their pooled analysis demonstrated that mortality was significantly lower in the tocilizumab group (RR=0.56 [0.34, 0.92]; p=0.02; I2=76%), as was the need for artificial invasive ventilation (RR=0.34 [0.12, 0.99]; p=0.05; I2=0%) as compared to the control group. No significant differences were observed between tocilizumab and control group in intensive care unit admissions (RR=0.73 [0.15, 3.59]; p=0.70; I2=60%) and risks of post-drug infection (RR=1.29 [0.41, 4.04]; p=0.66; I2=88%). In terms of efficacy outcome, improved oxygen saturation (RR=1.13 [1.04, 1.65]; p=0.02; I2=0%) was reported to be markedly significant in tocilizumab patients when compared with the standard care group. Conclusions Our results based on pooled studies show tocilizumab to be safe and efficacious in reducing mortality among critically ill COVID-19 patients. However, due to the limited number of observational studies, the positive findings should be viewed cautiously and warrant further investigation.

Intracerebral hemorrhage outcomes in patients using direct oral anticoagulants versus vitamin K antagonists: a meta-analysis.

BACKGROUND: The objective of this paper is to assess the clinical outcomes between non-traumatic intracerebral hemorrhage(ICH) in patients using direct oral anticoagulants(DOAC) versus vitamin K antagonists(VKA) for non-valvular atrial fibrillation. We also evaluated the predictors of the poor post-ICH outcomes. METHODS: We have performed pooled meta-analysis to assess long-term clinical outcomes in patients with DOAC-ICH as compared to those with VKA-ICH. A systematic literature search was conducted by searching the full-text English literature in PubMed, EMBASE, and Cochrane databases for observational studies reporting outcomes on interest. MOOSE guidelines were used to collect data till December 31, 2019 and random effects analysis was carried out to account for heterogeneity. For outcomes, risk ratios(RR) and the mean differences were pooled using a random-effects model and weighted mean differences (WMDs), respectively. RESULTS: Seventeen studies met the inclusion criteria (n = 25,354 patients; DOAC-ICH arms = 5,631; VKA-ICH arm = 19,273). Patients with DOAC-ICH had smaller hematoma volumes (WMD=-9.59; 95%CI=-15.33--3.85; I2 = 68.6%) and reduced mortality rate at discharge (RR = 0.82; 95%CI = 0.71-0.96; I2 = 9.4%). There was no significant difference between the two groups in rate of hematoma expansion (RR = 0.79; 95%CI = 0.56-1.11; I2 = 50.9%), unfavorable functional outcome(Modified Rankin Scale) at discharge (RR = 0.82; 95%CI = 0.56-1.18; I2 = 80.2%), unfavorable outcome at 3-months (RR = 0.77; 95%CI = 0.56-1.06; I2 = 63.9), and mortality at 3-months (RR = 0.90; 95%CI = 0.73-1.10; I2 = 35∙8%). Multivariate meta-regression revealed that the average age of patient population had a significantly negative correlation with(RR=-0.202; p = 0.017) hematoma expansion. CONCLUSION: We conclude that use of DOAC is associated with reduced hematoma volume and mortality rate at discharge. Age is a predictor of the poor outcome of hematoma expansion.

Aspiration Thrombectomy Versus Stent Retriever Thrombectomy Alone for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Introduction This meta-analysis was conducted to assess the safety and efficacy of aspiration thrombectomy versus stent retriever thrombectomy for acute ischemic stroke (AIS). Methods We queried online databases for original studies comparing aspiration thrombectomy with stent retriever thrombectomy in patients with AIS. After article selection, data were extracted on multiple baseline characteristics and prespecified endpoints. Dichotomous data were presented as risk ratios (RRs) and corresponding 95% confidence intervals (CIs); continuous data as mean differences and 95% CIs. The data were pooled using a random-effects model. Subgroup analysis was conducted based on study type, site of occlusion, and age. Results We shortlisted nine relevant studies (n=1453 patients; n=690 receiving aspiration thrombectomy and n=763 receiving stent retriever thrombectomy). Meta-analysis demonstrated no significant difference between the two groups in the rates of successful recanalization (RR: 0.96 [0.87, 1.06]; p=0.42), excellent functional outcome (RR: 0.90 [0.80, 1.01]; p=0.06), or procedure time (weighted mean difference (WMD): -5.39 minutes [-11.81, 1.04]; p=0.10). However, when removing the study by Nishi et al., sensitivity analysis resulted in a significant reduction in procedure time with aspiration (WMD: -11.01 [-15.54, -6.49]; p<0.0001). No significant difference was observed in safety outcomes, including all-cause mortality (RR: 0.82 [0.57, 1.19]; p=0.30), intracranial hemorrhage (RR: 0.93 [0.55, 1.59]; p=0.80), symptomatic intracranial hemorrhage (RR: 0.72[0.42, 1.21]; p=0.57), or embolization to new territory (RR: 0.71 [0.42, 1.19]; p=0.19). Subgroup analysis revealed that aspiration thrombectomy led to significantly better outcomes in patients with a mean age ≤65 (RR: 1.15 [1.03, 1.29]; p=0.001), and stent retriever thrombectomy led to increased recanalization success in patients with a mean age >65 (RR: 0.89 [0.80, 1.00]; p=0.05). Conclusions Our updated meta-analysis reveals that both aspiration and stent retriever thrombectomy are comparably effective in the management of AIS. Shorter procedure times may potentially be attained with aspiration thrombectomy, and outcomes with each procedure may be age-dependent.

Transcatheter Versus Surgical Aortic Valve Replacement in Low-Surgical-Risk Patients: A Meta-Analysis of Randomized-Controlled Trials and Propensity-Matched Studies.

BACKGROUND: We performed a meta-analysis of randomized trials (RCT) and propensity-matched (PSM) studies comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) in low surgical risk patients. METHODS: Published studies including low-risk patients who underwent TAVI (n = 9068) or SAVR (n = 17,388) were included. Outcomes of interest were short-term (30-day) and mid-term (1-year) mortality and major complications. RESULTS: Short-term mortality was lower with TAVI vs. SAVR (1.8% vs. 2.8%, RR = 0.67, [0.56-0.80]). TAVI was associated with lower risk of atrial fibrillation (7.4% vs. 36.5%, RR = 0.21, [0.14-0.31]), and kidney injury (5.3% vs. 9%, RR = 0.45, [0.26-0.80]), but had higher incidence of vascular complications (5.5% vs. 1.4%, RR = 4.88 [1.47-16.18]), and permanent pacemaker implantation (14.9% vs. 3.4%, RR = 4.94 [3.03-8.08]). Stroke rates were similar between both interventions (1.7% vs. 2.2%, RR = 0.80 [0.54-1.18]). Mid-term all-cause mortality was similar in the pooled analysis for TAVI vs. SAVR (8.6% vs. 8.4%, RR = 0.90 [0.66-1.24]), but was lower with TAVI in RCTs (2.1% vs. 3.5%, RR = 0.61 [0.39-0.95]). Cardiovascular mortality was lower with TAVI (1.6% vs. 2.9%, RR = 0.55 [0.33-0.90]), but stroke (3% vs. 4.2%, RR = 0.69, [0.45-1.06]) and valve re-interventions rates (0.8% vs. 0.6%, RR = 1.28 [0.52-3.17]) were similar between both strategies. CONCLUSION: TAVI in low surgical risk patients is associated with lower short-term morbidity and mortality compared with SAVR.

Does the administration of sonothrombolysis along with tissue plasminogen activator improve outcomes in acute ischemic stroke? A systematic review and meta-analysis.

This meta-analysis was conducted to assess the safety and efficacy of sonothrombolysis along with intravenous recombinant tissue plasminogen activator, alteplase (IV rtPA), in the management of acute ischemic stroke. Electronic databases were searched under different meSH terms without the restriction of time and language. 1415 studies were analyzed and seven studies that matched the inclusion criteria were selected. Multiple safety and efficacy outcomes were extracted. Our pooled analysis demonstrated that there is no significant difference between sonothrombolysis group and control group in preventing mortality (RR 1.10 [0.81, 1.50]; p = 0.55; I2 = 0%) and intracranial hemorrhage (RR 1.11 [0.76, 1.63]; p = 0.59; i2 = 0%), however, among the efficacy outcomes; complete recanalization after 60-120 min was achieved more effectively in the sonothrombolysis group (RR 2.11 [1.48, 3.03]; p ≤ 0.0001; I2 = 0%). The rest of the efficacy outcomes like neurological improvement at 24 h (RR 1.20 [0.92, 1.57]; p = 0.18; I2 = 40%) and excellent functional outcome after 3 months (RR 1.19 [0.93, 1.52]; p = 0.17; I2 = 35%) showed no significant differences between the two groups. In subgroup analysis, we found that sonothrombolysis led to a better neurological improvement in patients who were less than 65 years of age (RR 1.20 [0.92, 1.57]; p = 0.05; I2 = 40%). Moreover, there were no significant differences in the following of the subgroups assessed: (a) microsphere or microbubble use, (b) Ultrasound frequency (2 MHz or < 2 MHz), (c) transcranial Doppler (TCD) duration (1 h or 2 h), (d) age (≤ 65 or > 65).

Trajectory of Improvement in Children and Adolescents With Chronic Migraine: Results From the Cognitive-Behavioral Therapy and Amitriptyline Trial.

We compared headache frequency trajectories between clinical trial participants who received cognitive-behavioral therapy (CBT) and amitriptyline (CBT+A) or headache education (HE) and amitriptyline (HE+A) to determine if there was a differential time course of treatment response between the groups. One hundred thirty-five patients (age 10-17 years) diagnosed with chronic migraine participated, attending 8 one-hour one-on-one CBT or HE sessions with a trained psychologist for 8 weekly sessions, 2 sessions at weeks 12 and 16, and a post-treatment visit at week 20. Participants kept daily headache diaries and completed take-home assignments between visits. Data from daily headache diaries are presented for each day and according to 28-day periods. Trajectories of improvement indicate initial decrease in headache days began during the first month of treatment, for both groups, and continued to decrease throughout treatment. The CBT+A group had greater daily improvement than the HE+A group. A significantly greater proportion of the CBT+A group had a ≥50% reduction in headache days each month, and a significantly greater proportion of the CBT+A group had ≤4 headache days per month in months 3 through 5. Results indicate the trajectory of decrease in headache days is significantly better for patients receiving CBT+A versus HE+A. PERSPECTIVE: This article presents daily information about headache frequency over a 20-week clinical trial. Youth with chronic migraine who received CBT+A improved faster than those in the control group. Findings provide clinicians with evidence-based expectations for treatment response over time and ways of monitoring treatment success. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT00389038.

Cognitive Behavioral Therapy plus Amitriptyline for Children and Adolescents with Chronic Migraine Reduces Headache Days to ≤4 Per Month.

OBJECTIVE: The objective of this secondary analysis of results from a previously published trial (Clinical Trials Registration Number: NCT00389038) in chronic migraine in children and adolescents was to examine if participants who received cognitive behavioral therapy and amitriptyline reached a greater level of reduction in headache frequency that no longer indicated a recommendation for preventive treatment as compared to those who received headache education and amitriptyline. BACKGROUND: Chronic migraine negatively affects children's home, school, and social activities. Preventive medication therapy is suggested for 5 or more headaches per month. Reduction to one headache day per week or less may suggest that preventive treatment is no longer indicated and provide a clinically relevant outcome for treatment efficacy and patient care. METHODS: Randomized study participants (N = 135) kept a daily record of their headache frequency during 20 weeks of treatment and during a 1 year follow-up period. Baseline headache frequency was determined at the end of a 28 day screening period. Post treatment frequency was determined at 20 weeks (N = 128 completed) and post treatment follow-up was measured 12 months later (N = 124 completed). A chi-square test of independence was conducted by treatment group and by time point to determine group differences in the proportion of headache days experienced. RESULTS: At 20 weeks (post treatment), 47% of the cognitive behavioral therapy plus amitriptyline group had ≤4 headache days per month compared to 20% of the headache education plus amitriptyline group, (P = .0011), and 32% of the cognitive behavioral therapy plus amitriptyline group had ≤3 headache days per month at 20 weeks compared to 16% of the headache education plus amitriptyline group, (P = .0304). At the month 12 follow-up, 72% of the cognitive behavioral therapy plus amitriptyline group had ≤4 headache days per month compared to 52% of the headache education plus amitriptyline group, (P = .0249), and 61% of the cognitive behavioral therapy plus amitriptyline group had ≤3 headache days per month at their month 12 follow-up compared to 40% of the headache education plus amitriptyline group, (P = .0192). CONCLUSIONS: Participants who received cognitive behavioral therapy and amitriptyline were more likely than participants who received headache education plus amitriptyline to reach the clinically meaningful outcome of less than or equal to 4 headache days per month at both time points. These results may help inform what treatment outcomes are possible for children and adolescents suffering from chronic migraine and provides further evidence for behavioral treatment to be considered as a key part of a first line treatment regimen.

Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial.

IMPORTANCE: Early, safe, effective, and durable evidence-based interventions for children and adolescents with chronic migraine do not exist. OBJECTIVE: To determine the benefits of cognitive behavioral therapy (CBT) when combined with amitriptyline vs headache education plus amitriptyline. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial of 135 youth (79% female) aged 10 to 17 years diagnosed with chronic migraine (≥15 days with headache/month) and a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points were assigned to the CBT plus amitriptyline group (n = 64) or the headache education plus amitriptyline group (n = 71). The study was conducted in the Headache Center at Cincinnati Children's Hospital between October 2006 and September 2012; 129 completed 20-week follow-up and 124 completed 12-month follow-up. INTERVENTIONS: Ten CBT vs 10 headache education sessions involving equivalent time and therapist attention. Each group received 1 mg/kg/d of amitriptyline and a 20-week end point visit. In addition, follow-up visits were conducted at 3, 6, 9, and 12 months. MAIN OUTCOMES AND MEASURES: The primary end point was days with headache and the secondary end point was PedMIDAS (disability score range: 0-240 points; 0-10 for little to none, 11-30 for mild, 31-50 for moderate, >50 for severe); both end points were determined at 20 weeks. Durability was examined over the 12-month follow-up period. Clinical significance was measured by a 50% or greater reduction in days with headache and a disability score in the mild to none range (<20 points). RESULTS: At baseline, there were a mean (SD) of 21 (5) days with headache per 28 days and the mean (SD) PedMIDAS was 68 (32) points. At the 20-week end point, days with headache were reduced by 11.5 for the CBT plus amitriptyline group vs 6.8 for the headache education plus amitriptyline group (difference, 4.7 [95% CI, 1.7-7.7] days; P = .002). The PedMIDAS decreased by 52.7 points for the CBT group vs 38.6 points for the headache education group (difference, 14.1 [95% CI, 3.3-24.9] points; P = .01). In the CBT group, 66% had a 50% or greater reduction in headache days vs 36% in the headache education group (odds ratio, 3.5 [95% CI, 1.7-7.2]; P < .001). At 12-month follow-up, 86% of the CBT group had a 50% or greater reduction in headache days vs 69% of the headache education group; 88% of the CBT group had a PedMIDAS of less than 20 points vs 76% of the headache education group. Measured treatment credibility and integrity was high for both groups. CONCLUSIONS AND RELEVANCE: Among young persons with chronic migraine, the use of CBT plus amitriptyline resulted in greater reductions in days with headache and migraine-related disability compared with use of headache education plus amitriptyline. These findings support the efficacy of CBT in the treatment of chronic migraine in children and adolescents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00389038.

Quality of life and emotional functioning in youth with chronic migraine and juvenile fibromyalgia.

SUMMARY: Chronic pain in children is associated with significant negative impact on social, emotional, and school functioning. Previous studies on the impact of pain on children's functioning have primarily used mixed samples of pain conditions or single pain conditions (eg, headache and abdominal pain) with relatively small sample sizes. As a result, the similarities and differences in the impact of pain in subgroups of children with chronic pain have not been closely examined. OBJECTIVE: To compare pain characteristics, quality of life, and emotional functioning among youth with pediatric chronic migraine (CM) and juvenile fibromyalgia (JFM). METHODS: We combined data obtained during screening of patients for 2 relatively large intervention studies of youth (age range, 10 to 18 y) with CM (N=153) and JFM (N=151). Measures of pain intensity, quality of life (Pediatric Quality of Life; PedsQL, child and parent-proxy), depressive symptoms (Children's Depression Inventory), and anxiety symptoms (Adolescent Symptom Inventory-4-Anxiety subscale) were completed by youth and their parent. A multivariate analysis of covariance controlling for effects of age and sex was performed to examine differences in quality of life and emotional functioning between the CM and JFM groups. RESULTS: Youth with JFM had significantly higher anxiety and depressive symptoms, and lower quality of life in all domains. Among children with CM, overall functioning was higher but school functioning was a specific area of concern. DISCUSSION: Results indicate important differences in subgroups of pediatric pain patients and point to the need for more intensive multidisciplinary intervention for JFM patients.