What Is the Risk of Postoperative Neurologic Symptoms After Regional Anesthesia in Upper Extremity Surgery? A Systematic Review and Meta-analysis of Randomized Trials.

BACKGROUND: The risk of neurologic symptoms after regional anesthesia in orthopaedic surgery is estimated to approach 3%, with long-term deficits affecting 2 to 4 per 10,000 patients. However, current estimates are derived from large retrospective or observational studies that are subject to important systemic biases. Therefore, to harness the highest quality data and overcome the challenge of small numbers of participants in individual randomized trials, we undertook this systematic review and meta-analysis of contemporary randomized trials. QUESTIONS/PURPOSES: In this systematic review and meta-analysis of randomized trials we asked: (1) What is the aggregate pessimistic and optimistic risk of postoperative neurologic symptoms after regional anesthesia in upper extremity surgery? (2) What block locations have the highest and lowest risk of postoperative neurologic symptoms? (3) What is the timing of occurrence of postoperative neurologic symptoms (in days) after surgery? METHODS: We searched Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Web of Science, Scopus, and PubMed for randomized controlled trials (RCTs) published between 2008 and 2019 that prospectively evaluated postoperative neurologic symptoms after peripheral nerve blocks in operative procedures. Based on the Grading of Recommendations, Assessment, Development, and Evaluation guidance for using the Risk of Bias in Non-Randomized Studies of Interventions tool, most trials registered a global rating of a low-to-intermediate risk of bias. A total of 12,532 participants in 143 trials were analyzed. Data were pooled and interpreted using two approaches to calculate the aggregate risk of postoperative neurologic symptoms: first according to the occurrence of each neurologic symptom, such that all reported symptoms were considered mutually exclusive (pessimistic estimate), and second according to the occurrence of any neurologic symptom for each participant, such that all reported symptoms were considered mutually inclusive (optimistic estimate). RESULTS: At any time postoperatively, the aggregate pessimistic and optimistic risks of postoperative neurologic symptoms were 7% (915 of 12,532 [95% CI 7% to 8%]) and 6% (775 of 12,532 [95% CI 6% to 7%]), respectively. Interscalene block was associated with the highest risk (13% [661 of 5101] [95% CI 12% to 14%]) and axillary block the lowest (3% [88 of 3026] [95% CI 2% to 4%]). Of all symptom occurrences, 73% (724 of 998) were reported between 0 and 7 days, 24% (243 of 998) between 7 and 90 days, and 3% (30 of 998) between 90 and 180 days. Among the 31 occurrences reported at 90 days or beyond, all involved sensory deficits and four involved motor deficits, three of which ultimately resolved. CONCLUSION: When assessed prospectively in randomized trials, the aggregate risk of postoperative neurologic symptoms associated with peripheral nerve block in upper extremity surgery was approximately 7%, which is greater than previous estimates described in large retrospective and observational trials. Most occurrences were reported within the first week and were associated with an interscalene block. Few occurrences were reported after 90 days, and they primarily involved sensory deficits. Although these findings cannot inform causation, they can help inform risk discussions and clinical decisions, as well as bolster our understanding of the evolution of postoperative neurologic symptoms after regional anesthesia in upper extremity surgery. Future prospective trials examining the risks of neurologic symptoms should aim to standardize descriptions of symptoms, timing of evaluation, classification of severity, and diagnostic methods. LEVEL OF EVIDENCE: Level I, therapeutic study.

Persistent High Non-High-Density Lipoprotein Cholesterol in Early Childhood: A Latent Class Growth Model Analysis.

OBJECTIVES: To examine patterns of non-high-density lipoprotein (HDL) cholesterol in early childhood and identify factors associated with persistent high non-HDL cholesterol in healthy urban children. STUDY DESIGN: We identified all children enrolled in a primary care practice-based research network called TARGet Kids! (The Applied Research Group for Kids) with ≥3 laboratory measurements of non-HDL cholesterol. Latent class growth model analysis was performed to identify distinct trajectory groups for non-HDL cholesterol. Trajectory groups were then categorized into "normal" vs "persistent-high" non-HDL cholesterol based on guideline cut-off values and logistic regression was completed to examine the association between trajectory group and the presence of anthropometric and cardiometabolic risk factors. RESULTS: A total of 608 children met inclusion criteria for the trajectory analysis (median age at enrolment = 18.3, IQR = 27.9 months). Four trajectory groups were identified with 2 groups (n = 451) categorized as normal non-HDL cholesterol and 2 groups (n = 157) as persistent high non-HDL cholesterol. Family history of high cholesterol (OR 2.04, 95% CI 1.27-3.28) was associated significantly with persistent high non-HDL cholesterol, whereas East/Southeast Asian vs European ethnicity (OR 0.33, 95% CI 0.14-0.78), longer breastfeeding duration (OR 0.96, 95% CI 0.93-1.00), and greater birth weight (OR 0.69, 95% CI 0.48-1.00) were associated with lower odds of persistent high non-HDL cholesterol. CONCLUSIONS: Patterns of non-HDL cholesterol are identified during early childhood, and family history of high cholesterol was associated most strongly with persistent high non-HDL cholesterol. Future research should inform the development of a clinical prediction tool for lipids in early childhood to identify children who may benefit from interventions to promote cardiovascular health.

Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis.

OBJECTIVES: Heterozygous familial hypercholesterolaemia (FH) confers a significant risk for premature cardiovascular disease (CVD). However, the estimated prevalence of FH varies substantially among studies. We aimed to provide a summary estimate of FH prevalence in the general population and assess variations in frequency across different sociodemographic characteristics. SETTING, PARTICIPANTS AND OUTCOME MEASURES: We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO and PubMed for peer-reviewed literature using validated strategies. Results were limited to studies published in English between January 1990 and January 2017. Studies were eligible if they determined FH prevalence using clinical criteria or DNA-based analyses. We determined a pooled point prevalence of FH in adults and children and assessed the variation of the pooled frequency by age, sex, geographical location, diagnostic method, study quality and year of publication. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were investigated through subgroups, meta-regression and sensitivity analyses. RESULTS: The pooled prevalence of FH from 19 studies including 2 458 456 unique individuals was 0.40% (95% CI 0.29% to 0.52%) which corresponds to a frequency of 1 in 250 individuals. FH prevalence was found to vary by age and geographical location but not by any other covariates. Results were consistent in sensitivity analyses. CONCLUSIONS: Our systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals. These findings underscore the need for early detection and management to decrease CVD risk.

Patterns of use for brand-name versus generic oral bisphosphonate drugs in Ontario over a 13-year period: a descriptive study.

BACKGROUND: Bisphosphonates are the first-line therapy for the treatment of osteoporosis. In the province of Ontario, the Ontario Drug Benefit Program funds medications for patients aged 65 years and older. The Ontario Drug Benefit Program has a generic substitution policy that requires lower-cost generic drugs to be dispensed when they are available. However, there is controversy surrounding the efficacy and tolerability of generic bisphosphonates. The objective of this study was to describe patterns in the use of brand-name versus generic formulations when dispensing oral bisphosphonate over a 13-year period. METHODS: We identified all osteoporotic preparations for alendronate and risedronate that were dispensed through the Ontario Drug Benefit Program from 2001 to 2014. We stratified our sample into community-dwelling residents and residents in long-term care facilities. The number of prescriptions dispensed per month were plotted to illustrate trends over time. RESULTS: We found a rapid switch from brand-name to generic bisphosphonate equivalents immediately after the generic became available on the Ontario Drug Benefit formulary, with generics accounting for > 88% of dispensed drug within 2 months. We also observed a reduction in the number of generic drugs dispensed each time a new brand-name alternative (e.g., monthly risedronate, weekly alendronate plus vitamin D) was introduced to the formulary. The dispensing trends were similar in the community and long-term care settings. INTERPRETATION: The Ontario Drug Benefit Program generic substitution policy resulted in rapid uptake of generic oral bisphosphonates among seniors in Ontario. However, there was a switch away from generic medications to new brand-name alternatives whenever they were introduced to the formulary. Therefore, some patients continued to use brand-name bisphosphonate despite the availability of generic options.

Osteoporosis management among chronic glucocorticoid users: a systematic review.

BACKGROUND: Clinical practice guidelines recommend that all patients starting chronic oral glucocorticoid (GC) therapy receive bone mineral density (BMD) testing and osteoporosis pharmacotherapy. OBJECTIVE: We completed a systematic review of observational studies to examine the proportion of patients on chronic oral GC therapy who receive osteoporosis management. METHODS: Two independent reviewers completed a systematic search of Ovid MEDLINE® and EMBASE® to identify all English language articles that examined the prevalence of osteoporosis management among chronic oral GC users. Clinical trials, abstracts, reviews, commentaries, and letters to the editor were excluded. Study methods and results (use of BMD testing and osteoporosis pharmacotherapy) were abstracted and summarized by year and region. RESULTS: We identified 29 eligible studies published between 1999 and October 2013: 17 were conducted in North America, 5 in Europe, and 7 in other regions. Heterogeneity between patient populations and methods used to define chronic GC use precluded the direct comparison of results between regions, or over time. Over 80% of studies identified that < 40% of chronic oral GC users received BMD testing or osteoporosis pharmacotherapy. When results of these studies were plotted by year, there was little evidence of improvement in osteoporosis management over time. CONCLUSIONS: Despite consistent recommendations to target osteoporosis prevention at the onset of chronic oral GC therapy, osteoporosis is undermanaged among chronic oral GC users. Targeted interventions are needed to help reduce the burden of fracture-related morbidity associated with GC-induced osteoporosis.