The optimal treatment of type II and III odontoid fractures in the elderly: an updated meta-analysis.

PURPOSE: Odontoid fractures are the most common cervical spine fractures in the elderly, with a controversial optimal treatment. The objective of this review was to compare the outcome of surgical and conservative treatments in elderly (≥ 65 years), by updating a systematic review published by the authors in 2013. METHODS: A comprehensive search was conducted in seven databases. Clinical outcome was the primary outcome. Fracture union- and stability were secondary outcomes. Pooled point estimates and their respective 95% confidence intervals (CIs) were derived using the random-effects model. A random-effects multivariable meta-regression model was used to correct for baseline co-variates when sufficiently reported. RESULTS: Forty-one studies met the inclusion criteria, of which forty were case series and one a cohort study. No clinical differences in outcomes including the Neck Disability Index (NDI, 700 patients), Visual Analogue Scale pain (VAS, 180 patients), and Smiley-Webster Scale (SWS, 231 patients) scores were identified between surgical and conservative treatments. However, fracture union was higher in surgically treated patients (pooled incidence 72.7%, 95% CI 66.1%, 78.5%, 31 studies, 988 patients) than in conservatively treated patients (40.2%, 95% CI 32.0%, 49.0%, 22 studies, 912 patients). This difference remained after correcting for age and fracture type. Fracture stability (41 studies, 1917 patients), although numerically favoring surgery, did not appear to differ between treatment groups. CONCLUSION: While surgically treated patients showed higher union rates than conservatively treated patients, no clinically relevant differences were observed in NDI, VAS pain, and SWS scores and stability rates. These results need to be further confirmed in well-designed comparative studies with proper adjustment for confounding, such as age, fracture characteristics, and osteoporosis degree.

Complications and cosmetic outcomes of materials used in cranioplasty following decompressive craniectomy-a systematic review, pairwise meta-analysis, and network meta-analysis.

BACKGROUND: Optimal reconstruction materials for cranioplasty following decompressive craniectomy (DC) remain unclear. This systematic review, pairwise meta-analysis, and network meta-analysis compares cosmetic outcomes and complications of autologous bone grafts and alloplasts used for cranioplasty following DC. METHOD: PubMed, Embase, and Cochrane were searched from inception until April 2021. A random-effects pairwise meta-analysis was used to compare pooled outcomes and 95% confidence intervals (CIs) of autologous bone to combined alloplasts. A frequentist network meta-analysis was subsequently conducted to compare multiple individual materials. RESULTS: Of 2033 articles screened, 30 studies were included, consisting of 29 observational studies and one randomized control trial. Overall complications were statistically significantly higher for autologous bone compared to combined alloplasts (RR = 1.56, 95%CI = 1.14-2.13), hydroxyapatite (RR = 2.60, 95%CI = 1.17-5.78), polymethylmethacrylate (RR = 1.50 95%CI = 1.08-2.08), and titanium (Ti) (RR = 1.56 95%CI = 1.03-2.37). Resorption occurred only in autologous bone (15.1%) and not in alloplasts (0.0%). When resorption was not considered, there was no difference in overall complications between autologous bone and combined alloplasts (RR = 1.00, 95%CI = 0.75-1.34), nor between any individual materials. Dehiscence was lower for autologous bone compared to combined alloplasts (RR = 0.39, 95%CI = 0.19-0.79) and Ti (RR = 0.34, 95%CI = 0.15-0.76). There was no difference between autologous bone and combined alloplasts with respect to infection (RR = 0.85, 95%CI = 0.56-1.30), migration (RR = 1.36, 95%CI = 0.63-2.93), hematoma (RR = 0.98, 95%CI = 0.53-1.79), seizures (RR = 0.83, 95%CI = 0.29-2.35), satisfactory cosmesis (RR = 0.88, 95%CI = 0.71-1.08), and reoperation (RR = 1.66, 95%CI = 0.90-3.08). CONCLUSIONS: Bone resorption is only a consideration in autologous cranioplasty compared to bone substitutes explaining higher complications for autologous bone. Dehiscence is higher in alloplasts, particularly in Ti, compared to autologous bone.

Comparison of Amitriptyline and US Food and Drug Administration-Approved Treatments for Fibromyalgia: A Systematic Review and Network Meta-analysis.

Importance: Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological agents approved by the US Food and Drug Administration (FDA) to treat fibromyalgia. Objective: To investigate the comparative effectiveness and acceptability associated with pharmacological treatment options for fibromyalgia. Data Sources: Searches of PubMed/MEDLINE, Cochrane Library, Embase, and Clinicaltrials.gov were conducted on November 20, 2018, and updated on July 29, 2020. Study Selection: Randomized clinical trials (RCTs) comparing amitriptyline or any FDA-approved doses of investigated drugs. Data Extraction and Synthesis: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Four independent reviewers extracted data using a standardized data extraction sheet and assessed quality of RCTs. A random-effects bayesian network meta-analysis (NMA) was conducted. Data were analyzed from August 2020 to January 2021. Main Outcomes and Measures: Comparative effectiveness and acceptability (defined as discontinuation of treatment owing to adverse drug reactions) associated with amitriptyline (off-label), pregabalin, duloxetine, and milnacipran (on-label) in reducing fibromyalgia symptoms. The following doses were compared: 60-mg and 120-mg duloxetine; 150-mg, 300-mg, 450-mg, and 600-mg pregabalin; 100-mg and 200-mg milnacipran; and amitriptyline. Effect sizes are reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% credible intervals (95% CrIs). Findings were considered statistically significant when the 95% CrI did not include the null value (0 for SMD and 1 for OR). Relative treatment ranking using the surface under the cumulative ranking curve (SUCRA) was also evaluated. Results: A total of 36 studies (11 930 patients) were included. The mean (SD) age of patients was 48.4 (10.4) years, and 11 261 patients (94.4%) were women. Compared with placebo, amitriptyline was associated with reduced sleep disturbances (SMD, -0.97; 95% CrI, -1.10 to -0.83), fatigue (SMD, -0.64; 95% CrI, -0.75 to -0.53), and improved quality of life (SMD, -0.80; 95% CrI, -0.94 to -0.65). Duloxetine 120 mg was associated with the highest improvement in pain (SMD, -0.33; 95% CrI, -0.36 to -0.30) and depression (SMD, -0.25; 95% CrI, -0.32 to -0.17) vs placebo. All treatments were associated with inferior acceptability (higher dropout rate) than placebo, except amitriptyline (OR, 0.78; 95% CrI, 0.31 to 1.66). According to the SUCRA-based relative ranking of treatments, duloxetine 120 mg was associated with higher efficacy for treating pain and depression, while amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life. Conclusions and Relevance: These findings suggest that clinicians should consider how treatments could be tailored to individual symptoms, weighing the benefits and acceptability, when prescribing medications to patients with fibromyalgia.

Effects of the COVID-19 pandemic on stroke response times: a systematic review and meta-analysis.

OBJECTIVES: COVID-19 presents a risk for delays to stroke treatment. We examined how COVID-19 affected stroke response times. METHODS: A literature search was conducted to identify articles covering stroke during COVID-19 that included time metrics data pre- and post-pandemic. For each outcome, pooled relative change from baseline and 95% CI were calculated using random-effects models. Heterogeneity was explored through subgroup analyses comparing comprehensive stroke centers (CSCs) to non-CSCs. RESULTS: 38 included studies reported on 6109 patients during COVID-19 and 14 637 patients during the pre-COVID period. Pooled increases of 20.9% (95% CI 5.8% to 36.1%) in last-known-well (LKW) to arrival times, 1.2% (-2.9% to 5.3%) in door-to-imaging (DTI), 0.8% (-2.9% to 4.5%) in door-to-needle (DTN), 2.8% (-5.0% to 10.6%) in door-to-groin (DTG), and 19.7% (11.1% to 28.2%) in door-to-reperfusion (DTR) times were observed during COVID-19. At CSCs, LKW increased by 24.0% (-0.3% to 48.2%), DTI increased by 1.6% (-3.0% to 6.1%), DTN increased by 3.6% (1.2% to 6.0%), DTG increased by 4.6% (-5.9% to 15.1%), and DTR increased by 21.2% (12.3% to 30.1%). At non-CSCs, LKW increased by 12.4% (-1.0% to 25.7%), DTI increased by 0.2% (-2.0% to 2.4%), DTN decreased by -4.6% (-11.9% to 2.7%), DTG decreased by -0.6% (-8.3% to 7.1%), and DTR increased by 0.5% (-31.0% to 32.0%). The increases during COVID-19 in LKW (p=0.01) and DTR (p=0.00) were statistically significant, as was the difference in DTN delays between CSCs and non-CSCs (p=0.04). CONCLUSIONS: Factors during COVID-19 resulted in significantly delayed LKW and DTR, and mild delays in DTI, DTN, and DTG. CSCs experience more pronounced delays than non-CSCs.

Intraoperative Magnetic Resonance Imaging for Low-Grade and High-Grade Gliomas: What Is the Evidence? A Meta-Analysis.

BACKGROUND: The benefit of intraoperative magnetic resonance imaging (iMRI) in gliomas remains unclear. We performed a meta-analysis of outcomes with iMRI-guided surgery in high-grade gliomas (HGGs) and low-grade gliomas (LGGs). METHODS: Databases were searched until November 29, 2018 for randomized controlled trials (RCTs) and observational studies (OBS) comparing iMRI use with conventional neurosurgery. Pooled risk ratios (RRs) or hazard ratios were evaluated with the random-effects model. Outcomes included extent of resection (EOR), gross total resection (GTR), progression-free survival (PFS), overall survival (OS), and length of surgery (LOS), stratified by study design and glioma grade. RESULTS: Fifteen articles (3 RCTs and 12 OBS) were included. In RCTs, GTR was higher in iMRI compared with conventional neurosurgery (RR, 1.42; 95% confidence interval [CI], 1.17-1.73; I2, 7%) overall, for LGGs (1.91; 95% CI, 1.19-3.06), but not HGGs (1.24; 95% CI, 0.89-1.73), with no difference in EOR, PFS, OS, and LOS. For OBS, GTR was higher (RR, 1.65; 95% CI, 1.43-1.90; I2, 4%) overall, and for LGGs (1.63; 95% CI, 1.17-2.28; I2, 0%) and HGGs (1.62; 95% CI, 1.36-1.92; I2, 19%). EOR was greater with iMRI (6%; 95% CI, 4%-8%; I2, 44%) overall, in LGGs (5%; 95% CI, 2%-8%; I2, 37%) and HGGs (7%; 95% CI, 4%-10%; I2, 13%). There was no difference in PFS, OS, and LOS with iMRI. CONCLUSIONS: IMRI use improved GTR in gliomas, including LGGs. However, no PFS and OS benefit was shown in the meta-analysis.

The prevalence of complications associated with lumbar and thoracic spinal deformity surgery in the elderly population: a meta-analysis.

BACKGROUND: The prevalence of spinal deformities increases with age, affecting between 30% and 68% of the elderly population (ages ≥65). The reported prevalence of complications associated with surgery for spinal deformities in this population ranges between 37% and 71%. Given the wide range of reported complication rates, the decision to perform surgery remains controversial. METHODS: A comprehensive search was conducted using PubMed, Embase, and Cochrane to identify studies reporting complications for spinal deformity surgery in the elderly population. Pooled prevalence estimates for individual complication types were calculated using the random-effects model. RESULTS: Of 5,586 articles, 14 met inclusion criteria. Fourteen complication types were reported, with at least 2 studies for each complication with the following pooled prevalence: reoperation (prevalence 19%; 95% CI, 9-36%; 107 patients); hardware failure (11%; 95% CI, 5-25%; 52 patients); infection (7%; 95% CI, 4-12%; 262 patients); pseudarthrosis (6%; 95% CI, 3-12%; 149 patients); radiculopathy (6%; 95% CI, 1-33%; 116 patients); cardiovascular event (5%; 95% CI, 1-32%; 121 patients); neurological deficit (5%; 95% CI, 2-15%; 248 patients); deep vein thrombosis (3%; 95% CI, 1-7%; 230 patients); pulmonary embolism (3%; 95% CI, 1-7%; 210 patients); pneumonia (3%; 95% CI, 1-11%; 210 patients); cerebrovascular or stroke event (2%; 95% CI, 0-9%; 85 patients); death (2%; 95% CI, 1-9%; 113 patients); myocardial infarction (2%; 95% CI, 1-6%; 210 patients); and postoperative hemorrhage (1%; 95% CI, 0-10%; 85 patients). CONCLUSIONS: Most complication types following spinal deformity surgery in the elderly had prevalence point estimates of <6%, while all were at least ≤19%. Additional studies are needed to further explore composite prevalence estimates and prevalence associated with traditional surgical approaches as compared to minimally-invasive procedures in the elderly.

The Safety and Efficacy of Tranexamic Acid in Adult Spinal Deformity Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: Major spinal corrective surgeries can be associated with critical intra-operative blood loss. The objective of this systematic review and meta-analysis was to assess the safety and efficacy of tranexamic acid (TXA), a commonly used antifibrinolytic agent, in adult spinal deformity (ASD) surgery, defined as fusion of five or more levels. METHODS: Articles from PubMed, Embase, Cochrane, and clinicaltrials.gov were screened using PRISMA guidelines through December 2018. Thromboembolic events, blood loss, and transfusion levels were primary outcomes of interest. Randomized controlled trials (RCTs) and observational studies (OBSs) with adult patients (≥ 18 years) were included. Continuous variables were analyzed using mean difference (MD) and categorical variables were analyzed using Peto odds ratio (OR), via random effects models. RESULTS: Of the 604 articles screened, seven studies (two RCTs and five cohort studies) were included. Incidence of thromboembolic events was not statistically significantly different between TXA (1 event/19) and placebo (0 events/13) in the RCT (Peto OR = 1.41, 95% CI 0.05-37.2; 32 patients; 1 study) and in the OBSs (TXA [2 events/135] vs control [0 events/72]; Peto OR = 1.09, 95% CI 0.16-7.61; p-heterogeneity = 0.85; 207 patients; 3 studies). Data from OBSs showed that the pooled MD was statistically significantly lower in the TXA group compared with the control group for intraoperative blood loss (MD: - 620.2 mL, 95% CI - 1066.6 to - 173.7; p-heterogeneity = 0.14; 228 patients; 4 studies) and total transfusion volume (MD: - 958.2 mL, 95% CI - 1867.5 to - 49.0; p-heterogeneity = 0.23; 93 patients; 2 studies). CONCLUSION: In this meta-analysis, TXA was not significantly associated with increased risk of thromboembolic events but was associated with lower intraoperative blood loss and lower total transfusion volumes in ASD surgery.

Fertility after transsphenoidal surgery in patients with prolactinomas: A meta-analysis.

Pituitary prolactinomas in women often lead to amenorrhea, galactorrhea, or infertility. The purpose of this study was to evaluate the effectiveness of transsphenoidal surgery (TSS) in restoring fertility in women with proloactinomas. A systematic search of the literature was conducted in accordance with PRISMA guidelines through 6/13/2017. PubMed, Embase, and Cochrane databases were utilized to select studies reporting on patients with pituitary prolactinomas removed via TSS. Outcomes extracted included pre- and post-operative rates of menses, lactation, and fertility. Pooled effect estimates were calculated using random-effects. After removal of duplicates, 900 articles remained, of which 14 were meta-analyzed. The mean difference between pre- and post-operative prolactin level was 186.9 (95% CI = 133.7, 240.1; I2 = 69.9%; P-heterogeneity<0.01; 7 studies). The pooled prevalence of pre-operative amenorrhea was 96% (95% CI = 92%, 98%; I2 = 45.8%; P-heterogeneity = 0.09; 11 studies) and significantly larger than post-operative amenorrhea of 40% (95% CI = 27%, 55%; P- I2 = 85%; heterogeneity<0.01; 11 studies); (P-interaction comparing the 2 groups <0.01). The pooled prevalence of pre-operative galactorrhea was 84% (95% CI = 74%, 90%; I2 = 66.9%; P-heterogeneity<0.01; 10 studies) and significantly larger than post-operative galactorrhea of 29% (95% CI = 17%, 44%; I2 = 76.5%; P-heterogeneity<0.01; 7 studies) (P-interaction<0.01). Univariate meta-regression on age, continent, publication year, study design, quality, duration, or timing revealed these covariates were not effect modifiers for any of the 3 outcomes (all P > 0.05). No evidence of publication bias was seen using Begg's and Egger's tests (all P > 0.05). Transsphenoidal surgery appeared to improve fertility measures in women with pituitary prolactinomas.

Headache Resolution After Rathke Cleft Cyst Resection: A Meta-Analysis.

OBJECTIVE: Rathke cleft cysts (RCC) are benign lesions of the sella that often present with headache. It is not currently well established whether surgical resection of RCC results in resolution of headache. We conducted a meta-analysis to examine the effect of RCC resection on headache resolution. METHODS: PubMed, EMBASE, and Cochrane databases were searched through June 2017 for articles that evaluated the effect of RCC resection on headache resolution. Pooled effect estimates were calculated using fixed-effects and random-effects models. RESULTS: Ten case series with 276 patients were included. Transsphenoidal surgery (TSS) was used to resect RCC in all of the studies. Only 1 patient in 1 study underwent transcranial surgery. Using the fixed effect model, the overall headache resolution prevalence was 71.7% (95% confidence interval [CI] 65.3%, 77.3%) among patients who underwent resection of RCC (I2 = 76.9%; P-heterogeneity < 0.01). Subgroup analysis based on center (P-interaction < 0.01) and continent (P < 0.01) showed a higher resolution in studies conducted in a single center (79.8%; 95% CI 73.7%, 84.8%) than in multiple centers (40.0%; 95% CI 26.9%, 54.8%) and a higher resolution in studies conducted in Asia (85.0%) than in Europe (61.5%) or North America (65.7%). Metaregression analysis was significant on mean follow-up time (slope = 0.03; P = 0.02), percentage of women (slope -0.05; P < 0.01), journal impact factor (slope 0.73; P < 0.01), and study quality (slope -0.99; P < 0.01) but not on mean age (P = 0.10). None of the above-mentioned results were significant when the random effects model was used. No evidence of publication bias was observed. CONCLUSION: This meta-analysis demonstrates that the resection of RCC in patients presenting with headache is associated with headache resolution.

Physiologic Growth Hormone-Replacement Therapy and Craniopharyngioma Recurrence in Pediatric Patients: A Meta-Analysis.

OBJECTIVE: A systematic review and meta-analysis were conducted to examine the effect of growth hormone-replacement therapy (GHRT) on the recurrence of craniopharyngioma in children. METHODS: PubMed, Embase, and Cochrane databases were searched through April 2017 for studies that evaluated the effect of GHRT on the recurrence of pediatric craniopharyngioma. Pooled effect estimates were calculated with fixed- and random-effects models. RESULTS: Ten studies (n = 3487 patients) met all inclusion criteria, including 2 retrospective cohorts and 8 case series. Overall, 3436 pediatric patients were treated with GHRT after surgery and 51 were not. Using the fixed effect model, we found that the overall craniopharyngioma recurrence rate was lower among children who were treated by GHRT (10.9%; 95% confidence interval 9.80%-12.1%; I2 = 89.1%; P for heterogeneity <0.01; n = 10 groups) compared with those who were not (35.2%; 95% confidence interval 23.1%-49.6%; I2 = 61.7%; P for heterogeneity = 0.11; n = 3); the P value comparing the 2 groups was <0.01. Among patients who were treated with GHRT, subgroup analysis revealed that there was a greater prevalence of craniopharyngioma recurrence among studies conducted outside the United States (P < 0.01), single-center studies (P < 0.01), lower impact factor studies (P = 0.03), or studies with a lower quality rating (P = 0.01). Using the random-effects model, we found that the results were not materially different except for when stratifying by GHRT, impact factor, or study quality; this led to nonsignificant differences. Both Begg's rank correlation test (P = 0.7) and Egger's linear regression test (P = 0.06) indicated no publication bias. CONCLUSIONS: This meta-analysis demonstrated a lower recurrence rate of craniopharyngioma among children treated with GHRT than those who were not.

Efficacy of transsphenoidal surgery in achieving biochemical cure of growth hormone-secreting pituitary adenomas among patients with cavernous sinus invasion: a systematic review and meta-analysis.

OBJECTIVES: Growth hormone-secreting pituitary adenomas in adults can result in severe craniofacial disfigurement and potentially fatal medical complications. Surgical resection leading to remission of the disease is dependent on complete surgical resection of the tumor. Lesions that invade the cavernous sinus may not be safely accessible via an endonasal transsphenoidal surgery (TSS), and the rates of biochemical remission of patients with residual disease vary widely in the literature. We conducted a meta-analysis to examine the prevalence of biochemical remission after TSS among patients with growth hormone-secreting pituitary adenomas with and without cavernous sinus invasion. METHODS: Embase, PubMed, and Cochrane Library databases were searched for relevant publications. Fourteen studies with 972 patients with biochemically confirmed growth hormone-secreting pituitary adenomas were included in the meta-analysis. RESULTS: The overall remission prevalence under a fixed-effect model was 47.6% (95% CI = 40.8-54.4%) for patients with invasive macroadenomas (I2 = 74.6%, p < 0.01); 76.4% (95% CI = 72.2-80.1%) for patients with non-invasive macroadenomas (I2 = 59.6%, p = 0.03); and 74.2% (95% CI = 66.3-80.7%) for patients with non-invasive microadenomas (I2 = 36.4, p = 0.10). The significant difference among the three groups resulted from the difference between patients with or without cavernous sinus invasion (p = 0.01) and not from the size of adenomas among those without cavernous sinus invasion (p = 0.66). DISCUSSION: The prevalence of biochemical remission in patients with cavernous sinus invasion was lower than in patients without cavernous sinus invasion after TSS for acromegaly.