Inappropriate Use of Proton Pump Inhibitor Among Elderly Patients in British Columbia: What are the Long-term Adverse Events?

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most used classes of drugs. For most indications, PPIs are only recommended up to 8 weeks duration. However, PPI use continues to expand. Regular and prolonged use of PPIs should be avoided because of the risk of adverse events. OBJECTIVES: The main objective of this study was to (1) investigate the extent of PPI usage in people aged 65 or older in the province of British Columbia (BC), Canada, (2) provide an overview of the harms associated with the long-term use of PPIs. METHODS: We examined utilization trends of the PPIs in BC since the year 2009 using PharmaNet, BC's medication dispensing database where the information is accessible to community pharmacists. We performed a comprehensive literature search for relevant reviews reporting harms associated with long-term use of PPIs. A search was conducted from January 2014 to June 2022. RESULTS: Between 2000 and 2018 BC's population grew by 20%, but the use of PPIs escalated to 257%. Of these older British Columbians, 62% had a cumulative exposure exceeding 2 years and 42% exceeded 5 years. This is alarming because the recommended treatment duration is 4-12 weeks for common indications including reflux esophagitis, and duodenal and gastric ulcers. Only 13.5% were dispensed PPIs for 90 days or less. Patients on long-term PPI therapy should be reassessed. Adverse events of PPI use are common among older adults. We identified over 217 systematic reviews published during the last 8 years of specific harms associated with long-term daily usage of PPIs. These harms include increased risks of death, cardiovascular disease, acute renal injury, chronic kidney disease, dementia, fractures, hypomagnesemia, iron deficiency, vitamin B12 deficiency, enteric infection (including C. difficile), pneumonia, and neoplasia (gastric cancer, carcinoids, and colon cancer), and drug interactions. CONCLUSION: This study revealed a high prevalence of PPI use among elderly populations in BC, Canada. The overutilization of PPIs is often a result of failure to re-evaluate the need for continuation of therapy. Published studies identified signals of serious harm from long-term PPI exposure. Healthcare providers with patients can reverse the relentless expansion of long-term PPI exposure by discussing the expected benefits and potential harms.

Metastatic Breast Cancer to the Spine: Incidence of Somatic Gene Alterations and Association of Targeted Therapies With Overall Survival.

BACKGROUND: The increase in use of targeted systemic therapies in cancer treatments has catalyzed the importance of identifying patient- and tumor-specific somatic mutations, especially regarding metastatic disease. Mutations found to be most prevalent in patients with metastatic breast cancer include TP53, PI3K, and CDH1. OBJECTIVE: To determine the incidence of somatic mutations in patients with metastatic breast cancer to the spine (MBCS). To determine if a difference exists in overall survival (OS), progression-free survival, and progression of motor symptoms between patients who do or do not undergo targeted systemic therapy after treatment for MBCS. METHODS: This is a retrospective study of patients with MBCS. Review of gene sequencing reports was conducted to calculate the prevalence of various somatic gene mutations within this population. Those patients who then underwent treatment (surgery/radiation) for their diagnosis of MBCS between 2010 and 2020 were subcategorized. The use of targeted systemic therapy in the post-treatment period was identified, and post-treatment OS, progression-free survival, and progression of motor deficits were calculated for this subpopulation. RESULTS: A total of 131 patients were included in the final analysis with 56% of patients found to have a PI3K mutation. Patients who received targeted systemic therapies were found to have a significantly longer OS compared with those who did not receive targeted systemic therapies. CONCLUSION: The results of this study demonstrate that there is an increased prevalence of PI3K mutations in patients with MBCS and there are a significant survival benefit and delay in progression of motor symptoms associated with using targeted systemic therapies for adjuvant treatment.

Utilization of Vertebroplasty/Kyphoplasty in the Management of Compression Fractures: National Trends and Predictors of Vertebroplasty/Kyphoplasty.

OBJECTIVE: The purpose of this study is to examine the utilization of kyphoplasty/vertebroplasty procedures in the management of compression fractures. With the growing elderly population and the associated increase in rates of osteoporosis, vertebral compression fractures have become a daily encounter for spine surgeons. However, there remains a lack of consensus on the optimal management of this patient population. METHODS: A retrospective analysis of 91 million longitudinally followed patients from 2016 to 2019 was performed using the PearlDiver Patient Claims Database. Patients with compression fractures were identified using International Classification of Disease, 10th Revision codes, and a subset of patients who received kyphoplasty/vertebroplasty were identified using Common Procedural Terminology codes. Baseline demographic and clinical data between groups were acquired. Multivariable regression analysis was performed to determine predictors of receiving kyphoplasty/vertebroplasty. RESULTS: A total of 348,457 patients with compression fractures were identified with 9.2% of patients receiving kyphoplasty/vertebroplasty as their initial treatment. Of these patients, 43.5% underwent additional kyphoplasty/vertebroplasty 30 days after initial intervention. Patients receiving kyphoplasty/vertebroplasty were significantly older (72.2 vs. 67.9, p < 0.05), female, obese, had active smoking status and had higher Elixhauser Comorbidity Index scores. Multivariable analysis demonstrated that female sex, smoking status, and obesity were the 3 strongest predictors of receiving kyphoplasty/vertebroplasty (odds ratio, 1.27, 1.24, and 1.14, respectively). The annual rate of kyphoplasty/vertebroplasty did not change significantly (range, 8%-11%). CONCLUSION: The majority of vertebral compression fractures are managed nonoperatively. However, certain patient factors such as smoking status, obesity, female sex, older age, osteoporosis, and greater comorbidities are predictors of undergoing kyphoplasty/vertebroplasty.

Association between Vitamin D Status and Risk of Developing Severe COVID-19 Infection: A Meta-Analysis of Observational Studies.

OBJECTIVE: The relationship between 25-hydroxyvitamin D3 (25(OH)D), the surrogate marker for vitamin D3, serum concentration and COVID-19 has come to the forefront as a potential pathway to improve COVID-19 outcomes. The current evidence remains unclear on the impact of vitamin D status on the severity and outcomes of COVID-19 infection. To explore possible association between low 25(OH)D levels and risk of developing severe COVID-19 (i.e. need for invasive mechanical ventilation, the length of hospital stay, total deaths). We also aimed to understand the relationship between vitamin D insufficiency and elevated inflammatory and cardiac biomarkers. METHODS: We conducted a comprehensive electronic literature search for any original research study published up to March 30, 2021. For the purpose of this review, low vitamin D status was defined as a range of serum total 25(OH)D levels of <10 to <30 ng/ml. Two independent investigators assessed study eligibility, synthesized evidence, analyzed, critically examined, and interpreted herein. RESULTS: Twenty-four observational studies containing 3637 participants were included in the meta-analysis. The mean age of the patients was 61.1 years old; 56% were male. Low vitamin D status was statistically associated with higher risk of death (RR, 1.60 (95% CI, 1.10-2.32), higher risk of developing severe COVID-19 pneumonia (RR: 1.50; 95% CI, 1.10-2.05). COVID-19 patients with low vitamin D levels had a greater prevalence of hypertension and cardiovascular diseases, abnormally high serum troponin and peak D-dimer levels, as well as elevated interleukin-6 and C-reactive protein than those with serum 25(OH)D levels ≥30 ng/ml. CONCLUSIONS: In this meta-analysis, we found a potential increased risk of developing severe COVID-19 infection among patients with low vitamin D levels. There are plausible biological mechanisms supporting the role of vitamin D in COVID-19 severity. Randomized controlled trials are needed to test for potential beneficial effects of vitamin D in COVID-19 outcomes.

Effect of atorvastatin on testosterone levels.

BACKGROUND: Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial. OBJECTIVES: Primary objective To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment. Secondary objectives To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work. SELECTION CRITERIA: RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 µmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels. AUTHORS' CONCLUSIONS: We found no significant difference between atorvastatin and placebo on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.

Comparative Safety of Smoking Cessation Pharmacotherapies During a Government-Sponsored Reimbursement Program.

INTRODUCTION: The British Columbia Ministry of Health launched a Smoking Cessation Program on September 30, 2011, providing financial coverage for smoking cessation pharmacotherapies. Although pharmacotherapies have been shown to have a moderate short-term benefit as a quitting aid, substantial cardiovascular and neuropsychiatric safety concerns have been identified in adverse-reporting databases, leading to prescription label warnings by Health Canada and the U.S. Food and Drug Administration. However, recent studies indicate these warnings may be without merit. This study examined the comparative safety of medications commonly used to aid smoking cessation. AIMS AND METHODS: Population-based retrospective cohort study using B.C. administrative data to assess the relative safety between varenicline, bupropion, and nicotine replacement therapies (NRTs). The primary outcome was a composite of cardiovascular hospitalizations. Secondary outcomes included mortality, a composite of neuropsychiatric hospitalizations, and individual components of the primary outcome. Statistical analysis used propensity score-adjusted log-binomial regression models. A sensitivity analysis excluded patients with a history of cardiovascular disease. RESULTS: The study included 116 442 participants. Compared with NRT, varenicline was associated with a 10% 1-year relative risk decrease of cardiovascular hospitalization (adjusted risk ratio [RR] = 0.90, 95% confidence interval (CI): 0.82 to 1.00), a 20% 1-year relative risk decrease of neuropsychiatric hospitalization (RR: 0.80, CI: 0.7 to 0.89), and a 19% 1-year relative risk decrease of mortality (RR: 0.81, CI: 0.71 to 0.93). We found no significant association between NRT and bupropion for cardiovascular hospitalizations, neuropsychiatric hospitalizations, or mortality. CONCLUSIONS: Compared with NRT, varenicline is associated with fewer serious adverse events and bupropion the same number of serious adverse events. IMPLICATIONS: This study addresses the need for comparative safety evidence in a real-world setting of varenicline and bupropion against an active comparator. Compared with NRT, varenicline was associated with a decreased risk of mortality, serious cardiovascular events, and neuropsychiatric events during the treatment, or shortly after the treatment, in the general population of adults seeking pharmacotherapy to aid smoking cessation. These results provide support for the removal of the varenicline boxed warning for neuropsychiatric events and add substantively to the cardiovascular safety findings of previous observational studies and randomized clinical trials.

Back to the future: surgical rehearsal platform technology as a means to improve surgeon-patient alliance, patient satisfaction, and resident experience.

OBJECTIVE: Informed consent, when performed appropriately, serves many roles beyond simply obtaining the prerequisite medicolegal paperwork to perform a surgery. Prior studies have suggested that patient understanding is poor when verbal communication is the sole means of education. Virtual reality platforms have proven effective in enhancing medical education. No studies exist that have demonstrated the utility of virtual reality-facilitated informed consent (VR-IC) in improving the physician-patient alliance. The aim of this study was to determine the utility of VR-IC among patients providing consent for surgery and the impact of this educational and information technology-based strategy on enhancing the physician-patient alliance, patient satisfaction, and resident-physician perception of the consent process. METHODS: Prospective, single-site, pre- and postconsent surveys were administered to assess patient and resident perception of informed consent performed with the aid of VR-IC at a large tertiary academic medical center in the US. Participants were adult patients (n = 50) undergoing elective surgery for tumor resection and neurosurgical residents (n = 19) who obtained patient informed consent for these surgical procedures. Outcome measures included scores on the Patient-Doctor Relationship Questionnaire (PDRQ-9), the modified Satisfaction with Simulation Experience Scale, and the Maslach Burnout Inventory. Patient pre- and postconsent data were recorded in real time using a secure online research data platform (REDCap). RESULTS: A total of 48 patients and 2 family members provided consent using VR-IC and completed the surveys pre- and postconsent; 47.9% of patients were women. The mean patient age was 57.5 years. There was a statistically significant improvement from pre- to post-VR-IC consent in patient satisfaction scores. Measures of patient-physician alliance, trust, and understanding of their illness all increased. Among the 19 trainees, perceived comfort and preparedness with the informed consent process significantly improved. CONCLUSIONS: VR-IC led to improved patient satisfaction, patient-physician alliance, and patient understanding of their illness as measured by the PDRQ-9. Using VR-IC contributed to residents' increased comfort in the consent-gathering process and handling patient questions. In an era in which satisfaction scores are directly linked with hospital and service-line outcomes and reimbursement, positive results from VR-IC may augment physician and hospital satisfaction scores in addition to increasing measures of trust between physicians and patients.

Outcomes and Clinical Characteristics of Intracranial Hemorrhage in Patients with Hematologic Malignancies: A Systematic Literature Review.

BACKGROUND: Many clinical and demographic factors can influence survival of patients with hematologic malignancies who have intracranial hemorrhages (ICHs). Understanding the influence of these factors on patient survival can guide treatment decisions and may inform prognostic discussions. We conducted a systematic literature review to determine survival of patients with intracranial hemorrhages and concomitant hematologic malignancy. METHODS: A systematic literature review was conducted and followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. PubMed/MEDLINE, Web of Science, Ovid, SCOPUS, and Embase databases were queried with the following terms: ("intracranial hemorrhages" OR "brain hemorrhage" OR "cerebral hemorrhage" OR "subdural hematoma" OR "epidural hematoma" OR "intraparenchymal hemorrhage") AND ("Hematologic Neoplasms" OR "Myeloproliferative Disorders" OR "Myelofibrosis" OR "Essential thrombocythemia" OR "Leukemia"). Abstracts and articles were screened according to inclusion and exclusion criteria that were determined a priori. RESULTS: Literature review yielded 975 abstracts from which a total of 68 full-text articles were reviewed. Twelve articles capturing 634 unique patients were included in the final qualitative analysis. Median overall survival for all patients ranged from 20 days to 1.5 months while median overall survival for the subset of patients having ICH within 10 days of diagnosis of hematologic malignancy was 5 days. Intraparenchymal hemorrhages, multiple foci of hemorrhage, transfusion-resistant low platelet counts, leukocytosis, low Glasgow Coma Scale scores at presentation, and ICH early in treatment course were associated with worse outcomes. CONCLUSIONS: Survival for patients with hematologic malignancies and concomitant ICHs remains poor. Early detection, recognition of poor prognostic factors, and correction of hematologic abnormalities essential to prevention and treatment of ICHs in this patient population.

Validation of five search filters for retrieval of clinical practice guidelines produced low precision.

OBJECTIVES: The aim of the study was to validate search filters for retrieval of clinical practice guidelines (CPGs) in MEDLINE, Embase, and PubMed. STUDY DESIGN AND SETTING: A search for filters for identifying CPGs was conducted in Google and the InterTASC Information Specialists Sub-Group Search Filter Resource. To retrieve a random sample of CPGs to test sensitivity and precision of the filters, we used the TRIP and Epistemonikos databases. The citations were screened independently by two researchers. The sensitivity and precision were calculated. RESULTS: Five search filters were retrieved: two from the Canadian Agency for Drugs and Technologies in Health (CADTH), two from the University of Texas, and one from the MD Anderson Cancer Center Library. A total of 478 records were screened to identify 109 CPGs, which comprised the sample for testing sensitivity and precision. The sensitivity ranged from 87% to 98% for the five search filters and very low precision (<1%) across all databases. CONCLUSION: Knowledge users who are interested in retrieving all relevant CPGs can use the CADTH broad filter with the highest sensitivity. However, our analysis shows that it remains difficult to efficiently identify CPGs because of low precision of five search filters. We recommend searching guideline-specific resources as a more time-efficient approach than searching bibliographic databases.

Concordance of angiography and cerebral biopsy results for suspected primary central nervous system vasculitis: A multi-center retrospective review.

OBJECTIVE: Primary CNS Vasculitis (PCNSV) is a rare disease that is often challenging to diagnose. Cerebral angiography and biopsy have been utilized in the diagnostic workup for several decades but limited literature reports on the concordance of findings of angiography and biopsy. The primary objective of this work was to examine how cerebral angiography corresponded with biopsy findings in patients with suspected PCNSV. PATIENTS AND METHODS: A total of 128 patients who underwent workup for PCNSV between years 2005-2016 were identified by query of existing neurological surgery and angiography databases at University Hospitals Cleveland Medical Center (UHCMC) and the Cleveland Clinic Foundation (CCF). The primary outcome was to examine the concordance of results between angiography and cerebral biopsy. Secondary outcomes included examining concordance between results of biopsy and other commonly performed tests for diagnosis of PCNSV including Magnetic Resonance Imaging (MRI), cerebrospinal fluid white blood cell count (CSF WBC), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP). RESULTS: 128 patients underwent cerebral biopsy for diagnosis of suspected PCNSV. 93 (73%) of these patients also underwent angiography. Of the 34 patients with positive biopsy findings, only 5 also had positive angiography. Positive angiography was not found to be correlated with positive biopsy in our analysis. The only test that was significantly associated with biopsy proven vasculitis was increased CSF WBC count (P = 0.0114). CONCLUSIONS: PCNSV is a rare disease and often requires multiple tests or procedures to obtain definitive diagnosis. These results suggest that cerebral angiography findings are not associated with biopsy findings and should be used cautiously in the diagnostic work-up of PCNSV.

Influence of opioid prescribing standards on drug use among patients with long-term opioid use: a longitudinal cohort study.

BACKGROUND: In mid-2016, the College of Physicians and Surgeons of British Columbia (CPSBC) issued prescribing standards and guidelines relating to opioid drugs. We evaluated the impact of these regulatory standards and guidelines on prescription drug use among patients in the province with long-term opioid use. METHODS: We conducted a cohort study with monthly repeated measures using administrative health data in British Columbia. Patients with long-term prescription opioid use were followed for a 12-month prepolicy period and 10-month postpolicy period, and were compared with a historical control cohort. We excluded patients with a history of long-term care, palliative care or cancer. We estimated changes in use of opioids, high-dose opioids (> 90 mg of morphine equivalents/d), opioids with sedatives/hypnotics, and opioid discontinuation. RESULTS: The study population included 68 113 patients in the policy cohort and 68 429 patients in the historical control cohort. Following the introduction of the standards and guidelines, the average monthly use of opioids declined (adjusted difference -57 mg of morphine equivalents, 95% confidence interval [CI] -74 to -39) and discontinuation of opioids increased (odds ratio [OR] 1.24, 95% CI 1.16 to 1.32). Among patients prescribed high-dose opioids, switching to lower-dose opioids increased (OR 1.88, 95% CI 1.63 to 2.17), but discontinuation did not change significantly (OR 1.21, 95% CI 0.91 to 1.59). INTERPRETATION: The CPSBC's regulatory standards and guidelines were associated with modestly reduced opioid use and increased switching from high-dose to lower-dose opioids among patients with long-term use of prescribed opioids. Assessment of the potential impacts on health outcomes will be necessary for understanding the implications of the standards and guidelines.

Survival in Patients with High-Grade Spinal Meningioma: An Analysis of the National Cancer Database.

OBJECTIVE: To report baseline demographics and examine for differences in survival for patients with World Health Organization (WHO) grade II and III spinal meningioma. METHODS: The National Cancer Database was queried for patients diagnosed with WHO grade II or grade III spinal meningioma between 2004 and 2015. Cases with histopathological confirmation were included. Descriptive statistics were calculated and stratified by tumor type. Facility type, 30-day readmission, and 90-day mortality were also examined. Crude and adjusted Cox proportional hazards regression models were used to evaluate for differences in survival. RESULTS: A total of 287 patients with WHO grade II or grade III spinal meningioma (white, n = 237; black, n = 32; Asian and Pacific Islander, n = 11; unknown race, n = 7) were identified. The mean patient age was 56.4 years, and the majority were female (70%; n = 201). Almost one-half of the patients were treated in an academic/research program (45.3%; n = 130,). Those with WHO grade III lesions received the earliest treatment, at a mean of 10.8 days following diagnosis. The proportion of patients with unplanned 30-day readmission following surgery was 4.2% (n = 12). Two patients died within 90 days of surgery. Multivariable analysis demonstrated no differences in survival for patients with WHO grade II or grade III lesions (hazard ratio, 2.01; 95% confidence interval, 0.89-4.52; P = 0.09). CONCLUSIONS: No difference in overall survival was identified between patients with WHO grade II or III spinal meningioma, although a trend was seen toward worse survival for patients with WHO grade III lesions.

Racial/ethnic differences in survival for patients with gliosarcoma: an analysis of the National cancer database.

PURPOSE: Gliosarcoma is characterized by the World Health Organization as a Grade IV malignant neoplasm and a variant of glioblastoma. The association of race and ethnicity with survival has been established for numerous CNS malignancies, however, no epidemiological studies have reported these findings for patients with gliosarcoma. The aim of this study was to examine differences by race and ethnicity in overall survival, 30-day mortality, 90-day mortality, and 30-day readmission. METHODS: Data were obtained by query of the National Cancer Database (NCDB) for years 2004-2014. Patients with gliosarcoma were identified by International Classification of Diseases for Oncology, Third Edition (ICD-O-3)-Oncology morphologic code 9442/3 and topographical codes C71.0-C71.9. Differences in survival by race/ethnicity were examined using univariable and multivariable Cox proportional hazards models. Readmission and mortality outcomes were examined with univariable and multivariable logistic regression. RESULTS: A total of 1988 patients diagnosed with gliosarcoma were identified (White Non-Hispanic n = 1,682, Black Non-Hispanic n = 165, Asian n = 40, Hispanic n = 101). There were no differences in overall survival, 30- and 90-day mortality, or 30-day readmission between the races and ethnicities examined. Median survival was 10.4 months for White Non-Hispanics (95% CI 9.8, 11.2), 10.2 months for Black Non-Hispanics (95% CI 8.6, 13.1), 9.0 months for Asian Non-Hispanics (95% CI 5.1, 18.2), and 10.6 months for Hispanics (95% CI 8.3,16.2). 7.3% of all patients examined had an unplanned readmission within 30 days. CONCLUSION: Race/ethnicity are not associated with differences in overall survival, 30-day mortality, 90-day mortality, or 30-day readmission following surgical intervention for gliosarcoma.

Impact of Dual-Layer Duraplasty During Hemicraniectomy on Morbidity and Operative Metrics of Cranioplasty: A Retrospective Case-Control Study Comparing a Single-Layer with a Dual-Layer Technique.

BACKGROUND: Dural substitutes used during hemicraniectomy provide a barrier and dissection plane during subsequent cranioplasty. A recent review by our group showed that use of dural substitutes in hemicraniectomy is associated with reduction in estimated blood loss (EBL) and operative time (OT). In our experience, the use of a dual-layer technique facilitates a dissection plane with minimal adhesions. We hypothesized that use of this dual-layer technique would show decreased OT and EBL in patients undergoing cranioplasty. METHODS: We conducted a retrospective case-control study comparing use of single-layer versus dual-layer duraplasty on cranioplasty operative outcomes. Data on dual-layer cases were collected from patients who underwent cranioplasty from 2013 to 2017. These data were matched to controls from 2008 to 2012. Patients were identified by query of a neurosurgical database of all procedures performed at our institution. Patients were included if they had complete surgical records for cranioplasty. Cases and controls were compared with a Student t test, χ2 test, or Fisher exact test. RESULTS: A total of 78 controls and 45 cases met inclusion criteria. All baseline characteristics between cohorts were similar except for surgical indication. Mean OT (102.97 minutes vs. 102.18 minutes) and mean EBL were not significantly different (204.66 mL vs. 190 mL) between cohorts. CONCLUSIONS: In this study, we did not detect any significant difference between EBL and OT with use of single-layer versus dual-layer duraplasty. Mean EBL was slightly higher in the controls compared with cases but this difference was not statistically or clinically significant. This concept would benefit from a prospective randomized study.

Effect of Dural Substitute and Technique on Cranioplasty Operative Metrics: A Systematic Literature Review.

BACKGROUND: Cranioplasty after decompressive craniectomy can be associated with significant morbidity. Dural substitutes during the initial decompression could improve outcomes. METHODS: We performed a systematic literature review of online peer-reviewed databases to determine the effect of dural substitutes during decompressive craniectomy on operative metrics and outcomes after subsequent cranioplasty. RESULTS: Nine studies from 2006 to 2018 had reported the results from 922 patients undergoing autologous cranioplasty. Seven types of dural substitute were described, including biologic and synthetic materials. Compared with no graft, the use of dural substitutes was associated with significantly decreased operative times and surgical blood loss during subsequent cranioplasty. One study evaluated dual-layer substitutes and documented superior results compared with single layer. The most commonly reported complications were infection and cerebrospinal fluid leak; however, a significant reduction in complications was seen in only 1 study. CONCLUSIONS: The use of dural substitutes was associated with superior operative metrics, complication rates, and long-term outcomes.

A novel use of the NeuroBlate SideFire probe for minimally invasive disconnection of a hypothalamic hamartoma in a child with gelastic seizures.

The authors describe the case of a 22-month-old boy who presented with gelastic seizures and developmental delay. Magnetic resonance imaging and video-electroencephalography monitoring revealed a primarily intraventricular hypothalamic hamartoma and gelastic seizures occurring 20-30 times daily. The patient was treated with various regimens of antiepileptic medications for 16 months, but the seizures remained medically intractable. At 3 years of age, he underwent stereotactic laser ablation with an aim of disconnection of the lesion. The procedure was performed with the NeuroBlate SideFire probe. To the authors' knowledge, this is the first reported use of this technology for this procedure and serves as proof of concept. There were no perioperative complications, and 2 years postprocedure, the patient remains seizure free with marked behavioral and cognitive improvements.

Correction: Heterogeneity in Comparisons of Discontinuation of Tumor Necrosis Factor Antagonists in Rheumatoid Arthritis-A Meta-Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0168005.].

Heterogeneity in Comparisons of Discontinuation of Tumor Necrosis Factor Antagonists in Rheumatoid Arthritis - A Meta-Analysis.

OBJECTIVE: We did a systematic review of studies comparing discontinuation of tumor necrosis factor alpha (TNF) antagonists in rheumatoid arthritis (RA) patients, pooled hazard ratios and assessed clinical and methodological heterogeneity. METHODS: We searched MEDLINE and EMBASE until June 2015 for pairwise hazard ratios for discontinuing infliximab, etanercept, and adalimumab from cohorts of RA patients. Hazard ratios were pooled using inverse variance weighting and random effects estimates of the combined hazard ratio were obtained. Clinical and methodological heterogeneity was assessed using the between-subgroup I-square statistics and meta-regression. RESULTS: Twenty-four unique studies were eligible and large heterogeneity (I-square statistics > 50%) was observed in all comparisons. Type of data, location, and order of treatment (first or second line) modified the magnitude and direction of discontinuation comparing infliximab with either adalimumab or etanercept; however, some heterogeneity remained. No effect modifier was identified when adalimumab and etanercept were compared. CONCLUSION: Heterogeneity in studies comparing discontinuation of TNF antagonists in RA is partially explained by type of data, location, and order of treatment. Pooling hazard ratios for discontinuing TNF antagonists is inappropriate because largely unexplained heterogeneity was demonstrated when random effect estimates were calculated.

Prescriber preference for a particular tumour necrosis factor antagonist drug and treatment discontinuation: population-based cohort.

OBJECTIVE: To assess the effect of physician preference for a particular tumour necrosis factor α (TNF) antagonist on the risk of treatment discontinuation in rheumatoid arthritis. DESIGN: Population-based cohort study. SETTING: British Columbia administrative health data (inpatients, outpatients and pharmacy). PARTICIPANTS: 2742 British Columbia residents who initiated a first course of a TNF antagonist between 2001 and December 2008, had been diagnosed with rheumatoid arthritis, and were treated by 1 of 58 medium-volume to high-volume prescribers. INDEPENDENT VARIABLE: A level of physician preference for the drug (higher or lower) was assigned based on preceding prescribing records of the care-providing physician. Higher preference was defined as at least 60% of TNF antagonist courses initiated in the preceding year. Sensitivity analysis was conducted with different thresholds for higher preference. MAIN OUTCOME MEASURE: Drug discontinuation was defined as a drug-free interval of 180 days or switching to another TNF antagonist, anakinra, rituximab or abatacept. The risk of discontinuation was compared between different levels of physician preference using survival analysis. RESULTS: Higher preference for the prescribed TNF antagonist was associated with improved persistence with the drug (4.28 years (95% CI 3.70 to 4.90) vs 3.27 (2.84 to 3.84), with log rank test p value of 0.017). The adjusted HR for discontinuation was significantly lower in courses of drugs with higher preference (0.85 (0.76 to 0.96)). The results were robust in a sensitivity analysis. CONCLUSIONS: Higher physician preference was associated with decreased risk of discontinuing TNF antagonists in patients with rheumatoid arthritis. This finding suggests that physicians who strongly prefer a specific treatment help their patients to stay on treatment for a longer duration. Similar research on other treatments is warranted.