Surgical interventions and short-term outcomes for preterm infants with post-haemorrhagic hydrocephalus: a multicentre cohort study.

OBJECTIVE: To (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH). DESIGN: Cohort study of the Children's Hospitals Neonatal Database from 2010 to 2022. SETTING: 41 referral neonatal intensive care units (NICUs) in North America. PATIENTS: Infants born before 32 weeks' gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage. INTERVENTIONS: (1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS). MAIN OUTCOME MEASURES: Mortality and meningitis. RESULTS: Of 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort. CONCLUSIONS: There was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%.

Obese patients with new onset atrial fibrillation/flutter have higher risk of hospitalization, cardioversions, and ablations.

Obesity significantly increases the risk of developing atrial fibrillation (AF) and atrial flutter (AFL) and evidence from randomized trials indicates that weight loss may reduce the burden of AF/AFL in obese patients; however, the relationship between obesity and healthcare resource utilization in AF/AFL patients is lacking. We sought to assess this relationship in patients with newly diagnosed AF/AFL in a nationally representative cohort of the United States by using the MarketScan® claims database. International Classification of Diseases, Tenth Revision [ICD 10] diagnosis codes were used to select individuals with a new diagnosis of AF/AFL in 2017 and 2018, adjudicate baseline variables and to classify them according to obesity status. Patients were followed for two years at which point all data was censored. The primary outcome of the study was hospitalizations due to AF/AFL. Cox proportional hazards regression models were used to assess the adjusted hazard ratio for obese versus non-obese patients. There were 55,271 patients with new onset AF/AFL, which included 43,314 (78.4 %) who were non-obese and 11,957 (21.6 %) who were obese. There were significantly more males than females among non-obese (65.3 % vs. 34.7 %) and obese individuals (62.3 % vs. 37.7 %). The average age (SD) was similar in the non-obese (54.5 (9.7)) and obese cohorts (54.7 (8.4)), respectively. The incidence of Emergency Department visits (4.0 % vs. 6.5 %), hospitalizations (5.5 % vs. 10.7 %), cardioversions (6.6 % vs. 12.7 %), and ablation procedures (5.3 % vs. 8.6 %) were significantly increased among obese patients.

Industry Payments to US Physicians by Specialty and Product Type.

This study examines the distribution of payments within and across specialties and the medical products associated with the largest total payments.

Prediction of short- and long-term outcomes using pre-operative ventricular size in infants with post-hemorrhagic ventricular dilation.

PURPOSE: Post-hemorrhagic ventricular dilation (PHVD) leads to developmental delays in premature infants, yet the optimal timing of neurosurgical interventions is unknown. Neuroimaging modalities have emerged to delineate injury and follow the progression of PHVD. Fronto-temporal horn ratio (FTHR) is used as a marker of ventricular dilation and can be a standardized tool to direct the timing of neurosurgical intervention. Our study determined a pre-operative FTHR measurement threshold to predict short- and long-term outcomes. METHODS: This is a retrospective cohort study of premature infants with severe intraventricular hemorrhage (IVH) who developed PHVD requiring neurosurgical intervention and were treated in a level IV NICU between 2012 and 2019. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were performed to evaluate the accuracy of pre-operative FTHR for predicting developmental delay. In-hospital outcomes and developmental assessments were analyzed. RESULTS: We reviewed 121 charts of infants with IVH and identified 43 infants with PHVD who required neurosurgical intervention. We found FTHR measurements were an excellent predictor of cognitive and motor delay with an AUC of 0.89 and 0.88, respectively. An average pre-operative FTHR of ≥ 0.67 was also associated with worse lung and feeding outcomes. There was excellent inter-observer reliability of individual components of FTHR measurements. CONCLUSIONS: Early intervention for PHVD is ideal but not always practical. Identification of ventricular size thresholds associated with better outcomes is needed to direct timing of neurosurgical intervention.

Re-Analyses of 8 Historical Trials in Cardiovascular Medicine Assessing Multimorbidity Burden and Its Association with Treatment Response.

OBJECTIVE: The purpose of this study was to examine the multimorbidity burden of clinical trial participants and assess its association with treatment response. METHODS: We conducted a reanalysis of patient level data. There were 29,954 participants from 8 clinical trials containing 11 comparisons between an intervention and control condition. Patients were classified by Charlson Comorbidity Index (CCI) score. The primary outcomes were the primary study endpoints as originally specified for each trial. A Cox model that included the CCI score groups, the randomized group, and their interaction, was used to compare the primary outcome between randomized groups. The interaction term between randomized group and comorbidity index allowed the treatment effect to differ by level of comorbidity index and comprised the primary effect of interest. Hazard ratios and risk differences were reported for all comparisons. RESULTS: The mean CCI scores of trial populations ranged from 2.1 to 3.9 points, and the percentage of patients with scores ≥5 from 3% to 39%. Tests of interaction terms in models yielded P values ≤ .10 for 4/11 comparisons and ≤ .05 for 2/11 comparisons. In 3 additional comparisons, potentially important treatment variation on an absolute scale was observed despite interaction tests with P values > .10 on the relative scale. CONCLUSIONS: These trials were mainly composed of patient populations with CCI scores ≤4. Despite this, biologically plausible treatment interactions were commonly suggested. These results are hypothesis generating; confirmation of results would require larger studies or studies targeted specifically toward patients with higher levels of multimorbidity.

What Counts as a Surrogate Decision?

When patients lose decision-making capacity, others must make surrogate decisions on their behalf. What counts as a surrogate decision might seem self-evident. But as clinician-researchers in the field of advance care planning, we have found that it is not always so clear-cut. In this paper, we describe how and why this is a matter of concern, a novel approach for assessing whether a surrogate decision occurred, and findings from this assessment.

Relationships Between Personality Traits and Perceived Stress in Surrogate Decision-Makers of Intensive Care Unit Patients.

INTRODUCTION: Personality traits, specifically neuroticism, are related to stress in surrogate decision-makers (SDMs) in outpatient settings. We hypothesized that intrinsic traits are related to SDM stress in the intensive care unit (ICU) to determine if personality considerations should be included in interventions to support SDMs. METHODS: Eligible participants (adult SDMs of non-capacitated ICU patients) completed validated questionnaires including stress (Impact of Events Scale-Revised, IES-R) and personality (Big Five Inventory, BFI) within 72 hours of ICU admission and again at 3 months post-ICU discharge (in addition to a qualitative interview). Bivariate Pearson correlations explored the relationship between BFI and IES-R at each time point (95% CI) and t-tests explored the relationship between stress and COVID-19. Mixed-methods analysis integrated qualitative and quantitative data. RESULTS: Of 32 SDMs, 71.9% were female, 93.8% white, and 97.0% were family members. Neuroticism was not significantly correlated to IES-R at 72 hours (r = 0.09; p = 0.64), but r increased 3 months post-discharge (r = 0.32; p = 0.07). Other BFI traits did not show similar patterns. Total stress was greater in surrogates of COVID-19-positive patients (COVID-19-positive: 60.6; COVID-19-negative: 49.8; p = 0.025). Mixed-methods analysis demonstrated that participants with high neuroticism scores had poorer emotional regulation than those with low neuroticism scores. CONCLUSIONS: This study supports that personality, particularly neuroticism, influences the stress of SDMs in the ICU. Further study of personality traits may identify surrogates who are at higher risk of stress-related disorders, which can guide future interventions.

Awake craniotomy for supratentorial tumors or epileptogenic lesions in pediatric patients: a 16-year retrospective cohort study.

OBJECTIVE: Awake craniotomy with intraoperative mapping is the widely accepted procedure for adult patients undergoing supratentorial tumor or epileptogenic focus resection near eloquent cortex. In children, awake craniotomies are notably less common due to concerns for compliance and emotional or psychological repercussions. Despite this, successfully tolerated awake craniotomies have been reported in patients as young as 8 years of age, with success rates comparable to those of adults. The authors sought to describe their experience with pediatric awake craniotomies, including insight regarding feasibility and outcomes. METHODS: A retrospective review was completed for all pediatric (age < 18 years) patients at Children's Wisconsin for whom an awake craniotomy was attempted from January 2004 until March 2020. Institutional review board approval was granted. RESULTS: Candidate patients had intact verbal ability, cognitive profile, and no considerable anxiety concerns during neuropsychology assessment. Nine patients presented with seizure. Five patients were diagnosed with tumor and secondary epilepsy, 3 with tumor only, and 3 with epilepsy only. All patients who underwent preoperative functional MRI successfully completed and tolerated testing paradigms. A total of 12 awake craniotomies were attempted in 11 patients, with 1 procedure aborted due to intraoperative bleeding. One patient had a repeat procedure. The mean patient age was 15.5 years (range 11.5-17.9 years). All patients returned to or maintained baseline motor and speech functions by the latest follow-up (range 14-130 months). Temporary deficits included transient speech errors, mild decline in visuospatial reasoning, leg numbness, and expected hemiparesis. Of the 8 patients with a diagnosis of epilepsy prior to surgery, 7 patients achieved Engel class I designation at the 1-year follow-up, 6 of whom remained in class I at the latest follow-up. CONCLUSIONS: This study analyzes one of the largest cohorts of pediatric patients who underwent awake craniotomy for maximal safe resection of tumor or epileptogenic lesions. For candidate patients, awake craniotomy is safe, feasible, and effective in carefully selected children.

Controversies in Hypertension V: Resistant and Refractory Hypertension.

Apparent resistant hypertension, defined as uncontrolled office blood pressure despite ≥ 3 antihypertensive medications including a diuretic or use of ≥ 4 medications regardless of blood pressure, occurs in ≤ 15% of treated hypertensives. Apparent refractory hypertension, defined as uncontrolled office pressure despite use of 5 or more medications including a diuretic, occurs in ≤ 10% of resistant cases. Both are associated with increased comorbidity and enhanced cardiovascular risk. To rule out pseudo-resistant or pseudo-refractory hypertension, employ guideline-based methodology for obtaining pressure, maximize the regimen, rule out white-coat effect, and assess adherence. True resistant hypertension is characterized by volume overload and aldosterone excess, refractory by enhanced sympathetic tone. Spironolactone is the preferred agent for resistance, with lower doses. Spironolactone, potassium binders, or both, are preferred if the estimated glomerular filtration rate is below 45. If significant albuminuria, finerenone is indicated. The optimal treatment of refractory hypertension is unclear, but sympathetic inhibition (α-ß blockade, centrally acting sympathoinhibitors, or both) seems reasonable. Renal denervation has shown minimal benefit for resistance, but its role in refractory hypertension remains to be defined.

Student Perceptions of a New Course Using Argumentation in Medical Education.

Purpose: Critical thinking and the ability to engage with others of differing views in a civil manner is essential to the practice of medicine. A new format for medical student education ("Argue-to-Learn") that uses staged debates followed by small group discussions was introduced into the curriculum of first year medical school at the Penn State College of Medicine. The goal was to create a structured environment for spirited, civil discourse, and to encourage students to think critically about clinically controversial topics. This manuscript describes the development of the program, and presents comparative data on student perceptions of the first two mandatory sessions that focused on the treatment of post-menopausal osteoporosis and on COVID-19 vaccine mandates. Methods: Quantitative results were gathered from standardized post-block student surveys for each session and compared to cumulative results of all other courses included in the learning block. Post-block surveys of students include four session-evaluation questions scored on a 5 point Likert scale. Scores were compared using Student's t-test. Thematic analysis of qualitative data was performed on a single open-ended response from the same survey. Results: Compared to all other courses in the learning block, scores on each of the four questions were either the same or numerically higher for the Argue-to-Learn sessions, but none reached statistical significance. Two important qualitative themes were identified. First, students enjoyed the format, found it interesting and engaging and want more similar sessions. Second, students appreciated hearing opposing viewpoints and presenting their own viewpoints in a safe and supportive environment. Conclusion: These findings support evidence from educational scholarship outside of medicine showing argumentation as a learning tool is well received by students. Further work is needed to determine whether it improves critical thinking skills and enhances learning in medical education.

Prophylactic Spinal Cord Untethering in Children with Spinal Dysraphism Undergoing Thoracolumbar Fusion for Scoliosis.

BACKGROUND: It remains unclear whether spinal cord untethering is necessary to reduce the chances of neurologic decline in children with myelomeningocele and complex closed spinal dysraphism who undergo thoracolumbar fusion for scoliosis. We sought to determine the neurologic and functional outcomes of children with spinal dysraphism undergoing spinal fusion for scoliosis with and without prophylactic spinal cord untethering. METHODS: Retrospective, single-center review of patients with spinal dysraphism treated with thoracolumbar fusion over the last 10 years (2009-2019) with or without prophylactic spinal cord untethering. RESULTS: Seventeen patients with myelomeningocele and complex closed spinal dysraphism underwent spinal fusion for scoliosis. Mean age at time of surgery was 13.9 years. Prophylactic spinal cord untethering was performed in 8 of 17 (47%) patients. The change in Cobb angle after surgery was similar between the 2 groups (19.4° untethered vs. 19.9° no untethering). The ambulatory status was similar between the groups, with 37% of the untethered cohort and 44% of the non-untethered cohort being community or household ambulators. There were no changes in intraoperative motor or sensory evoked potentials in any patient during fusion surgery. No patient had a change in motor level or ambulatory status after scoliosis surgery. CONCLUSIONS: Our data suggest that prophylactic spinal cord untethering in children with spinal dysraphism undergoing thoracolumbar fusion for scoliosis may not be necessary in patients with moderate curvatures. Our conclusions are limited by the small sample size. A larger review of registry data may yield more powerful conclusions on the necessity of prophylactic spinal cord untethering in this patient population.

Controversies in Hypertension IV: Renal Denervation.

Renal denervation is not a cure for hypertension. Although more recent sham-controlled trials were positive, a significant minority of patients in each trial were unresponsive. The optimal patient or patients need to be defined. Combined systolic/diastolic hypertension appears more responsive than isolated systolic hypertension. It remains uncertain whether patients with comorbidities associated with higher adrenergic tone should be targeted, including obesity, diabetes, sleep apnea, and chronic kidney disease. No biomarker can adequately predict response. A key to a successful response is the adequacy of denervation, which currently cannot be assessed in real time. It is uncertain what is the optimal denervation methodology: radiofrequency, ultrasound, or ethanol injection. Radiofrequency requires targeting the distal main renal artery plus major branches and accessory arteries. Although denervation appears to be safe, conclusive data on quality of life, improved target organ damage, and reduced cardiovascular events/mortality are required before denervation can be generally recommended.

A systematic review and meta-analysis of all sham and placebo controlled trials for resistant hypertension.

INTRODUCTION: There is a lack of consensus regarding the best add on therapy for treatment of resistant hypertension (RH). This is likely secondary to a paucity of data on the comparative effectiveness of proposed therapies for RH. METHODS: Placebo-controlled and sham-controlled randomized clinical trials testing therapies for the treatment of RH were included in this meta-analysis. Therapies with two or more studies were included as subgroups in this meta-analysis. The primary outcomes being tested were 24-hr systolic blood pressure (SBP) and office SBP. RESULTS: Eight studies were identified that tested mineralocorticoid receptor antagonist (MRA) including 1,414 participants. The raw mean difference (RMD) between MRA and placebo control was statistically significant for 24-hour SBP (-10.56 mmHg; 95% confidence interval (CI) -12.82 to -8.30), 24-hour diastolic (DBP) (-5.48 mmHg; 95% CI -8.48 to -2.58), office SBP (-11.97 mmHg; 95% CI -16.41 to -7.54), and office DBP (-4.14 mmHg; 95% CI -5.62 to -2.65). Six studies were identified that tested renal denervation (RD) including 989 participants. The RMD between RD and sham control was not statistically significant for 24-hour SBP (-1.84 mmHg; 95% CI -3.92 to 0.24), 24-hour DBP (-0.66 mmHg; 95% CI -1.85 to 0.54), office SBP (-1.57 mmHg; 95% CI -6.04 to 2.89), and office DBP (-1.49 mmHg; 95% CI -3.52 to 0.55). Four studies were identified that tested endothelin receptor antagonists (ERA) including 1,193 participants. The raw mean difference (RMD) between ERA and placebo control was statistically significant for 24-hr systolic (SBP) (-7.02 mmHg; 95% CI -9.15 to -4.90, 24-hr diastolic (DBP) (-6.22 mmHg; 95% CI -7.61 to -4.82), office SBP (-5.84 mmHg; 95% CI -10.08 to -1.60), and office DBP (-3.73 mmHg; 95% CI -5.87 to -1.59). DISCUSSION: MRA lowers BP in patients with RH more than RD, which seems to have little to no effect in RH. ERAs lead to a statistically significant reduction in BP but the confidence in efficacy is limited due to the low number of studies and differences in trial population. Individual factors and their impact on treatment response in RH should be investigated in future research.

Variability in neurosurgical management and associated comorbidities and complications among preterm patients with posthemorrhagic hydrocephalus in the United States.

OBJECTIVE: Posthemorrhagic hydrocephalus (PHH) remains a major morbidity of premature birth resulting from intraventricular hemorrhage (IVH). National consensus guidelines for the timing of surgical interventions are lacking, which leads to considerable variations in management among neonatal intensive care units (NICUs). Early intervention (EI) has been shown to improve outcomes, but the authors hypothesized that the timing from IVH to intervention affects the comorbidities and complications associated with PHH management. The authors used a large national inpatient care data set to characterize comorbidities and complications associated with PHH management in premature infants. METHODS: The authors used hospital discharge data from the 2006-2019 Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) to conduct a retrospective cohort study of premature pediatric patients (weight < 1500 g) with PHH. The predictor variable was the timing of the PHH intervention (EI ≤ 28 days vs late intervention [LI] > 28 days). Hospital stay data included hospital region, gestational age, birth weight (BW), length of stay (LOS), PHH treatment procedures, comorbidities, surgical complications, and death. Statistical analysis included chi-square and Wilcoxon rank-sum tests, Cox proportional hazards regression, logistic regression, and a generalized linear model with Poisson and gamma distributions. Analysis was adjusted for demographic characteristics, comorbidities, and death. RESULTS: Of the 1853 patients diagnosed with PHH, 488 (26%) had documented timing of surgical interventions during their hospital stay. More patients had LI than EI (75%). The patients in the LI group of patients had younger gestational age and lower BW. There were significant regional differences in the timing of treatment: hospitals in the West performed EI, whereas hospitals in the South performed LI, even after adjustment for gestational age and BW. The LI group was associated with longer median LOS and more total hospital charges compared with the EI group. More temporary CSF diversion procedures occurred in the EI group, whereas more permanent CSF-diverting shunts were placed in the LI group. Shunt/device replacement and complications did not differ between the two groups. The LI group had 2.5-fold higher odds of sepsis (p < 0.001) and almost 2-fold higher odds of retinopathy of prematurity (p < 0.05) than the EI group. CONCLUSIONS: The timing of PHH interventions differs by region in the United States, whereas the association of potential benefits with treatment timing suggests the importance of national consensus guidelines. Development of these guidelines can be informed by data regarding treatment timing and patient outcomes available in large national data sets, which provide insights into comorbidities and complications of PHH interventions.

HOPE and DREAM: A Two-Clinic NICU Follow-up Model.

OBJECTIVE: The natural extension of inpatient-focused neonatal neurocritical care (NNCC) programs is the evaluation of long-term neurodevelopmental outcomes in the same patient population. CLINICAL DESIGN: A dedicated and collaborative team of neonatologists, neonatal neurologists, neuropsychologists, neurosurgeons, physical medicine and rehabilitation physicians, and psychologists are necessary to provide personalized medicine, developmental assessments, and parental education for NNCC graduates. To achieve this goal, we devised a two-clinic follow-up model at Children's Wisconsin: HOPE (Healthy Outcomes Post-ICU Engagement) and DREAM: Developmentally Ready: Engagement for Achievement of Milestones) clinics. Those infants with significant neurologic diagnoses attend DREAM clinic, while all other high-risk neonatal intensive care unit (NICU) infants are seen in the HOPE clinic. CONCLUSION: These clinic models allow for a targeted approach to post-NICU care, which has improved family engagement and perceptions of value. KEY POINTS: · Infants with neurologic compromise are a specialized population with increasing survival.. · Interdisciplinary NICU follow-up brings together previously separated outpatient service lines.. · Our novel clinic model allows for specialized developmental assessments..

Controversies in Hypertension III: Dipping, Nocturnal Hypertension, and the Morning Surge.

A comprehensive approach to hypertension requires out-of-office determinations by home or ambulatory monitoring. The 4 phenotypes comparing office and out-of-office pressures in treated and untreated patients include normotension, hypertension, white-coat phenomena, and masked phenomena. Components of out-of-office pressure may be equally as important as mean values. Nighttime pressures are normally 10%-20% lower than daytime (normal "dipping") pressures. Abnormalities include dipping more than 20% (extreme dippers), less than 10 % (nondippers), or rising above daytime (risers) and have been associated with elevated cardiovascular risk. Nighttime pressure may be elevated (nocturnal hypertension) in isolation or together with daytime hypertension. Isolated nocturnal hypertension theoretically changes white-coat hypertension to true hypertension and normotension to masked hypertension. Pressure normally peaks in the morning hours ("morning surge") when cardiovascular events are most common. Morning hypertension may result from residual nocturnal hypertension or an exaggerated surge and has been associated with enhanced cardiovascular risk, especially in Asian populations. Randomized trials are needed to determine whether altering therapy based solely on either abnormal dipping, isolated nocturnal hypertension, or an abnormal surge is justified.

A Subgroup Meta-Analysis Comparing the Renal Denervation Sham-Controlled Randomized Trials Among Those With Resistant and Nonresistant Hypertension.

Renal denervation (RD) has been investigated as an invasive blood pressure (BP) lowering treatment for hypertension (HTN). Resistant HTN (RHTN) has been defined as uncontrolled BP despite use of 3 antihypertensive medications of different classes, including a diuretic, at maximum tolerated doses. The impact of RD on RHTN remains under investigation. Ten sham-controlled trials testing RD were included in this trial-level analysis. A prespecified subgroup analysis was conducted to test whether efficacy of RD differed in patients with and without RHTN. The primary end points were change in 24-hour ambulatory systolic (SBP) and diastolic (DBP) using raw mean difference (RMD) between sham control and RD. Ten studies (6 RHTN and 4 nonresistant HTN) were identified that included 1,544 participants (1,001 RHTN and 543 essential HTN) with cumulative mean age (±SD) of 57 years (±3). Cochran risk of bias assessment showed 69% of the domains to be at low risk of bias. The RMD for 24-hour SBP between RD and sham control was statistically significant for nonresistant HTN trials (-4.19 mm Hg; 95% confidence interval [CI] -6.07 to -2.30) but was not statistically significant for RHTN trials (-1.86 mm Hg; 95% CI - 3.89 to 0.16). Despite the numerical difference in the subgroups, the interaction between subgroups failed to reach statistical significance (p = 0.10). The RMD for 24-hour DBP between RD and sham control was statistically significant for nonresistant HTN trials (-2.60 mm Hg; 95% CI -3.79 to -1.42) but was not statistically significant for RHTN trials (-0.67 mm Hg; 95% CI -1.84 to 0.50). The interaction between subgroups was statistically significant (p = 0.02). Our analysis indicates RD is a less effective intervention for patients with RHTN. These data may be beneficial for clinicians to consider when assessing patients with RHTN for RD.

Denosumab versus Bisphosphonates for Reducing Fractures in Postmenopausal Women with Osteoporosis: A Meta-Analysis.

BACKGROUND: There are multiple classes of pharmacologic agents approved for treatment of osteoporosis, but their costs vary widely, and systematic data on their efficacy compared with the traditional standard, bisphosphonates, for reducing fractures in postmenopausal women are lacking. The objective was to perform a systematic review and meta-analysis assessing the efficacy of denosumab compared with bisphosphonates. METHODS: Researchers selected randomized controlled trials (RCTs) comparing denosumab to bisphosphonates that included information on clinical and/or osteoporotic fracture events over the follow-up period. Each clinical outcome was meta-analyzed using a fixed-effects analysis, with clinical and osteoporotic fractures as the outcomes of interest. A meta-regression was performed using change in bone mineral density (BMD) as the moderator variable. RESULTS: Seven RCTs were included. Denosumab was not associated with a reduction in clinical or osteoporotic fractures compared with bisphosphonates. There was no association between the change in BMD with denosumab and bisphosphonates and denosumab's effect on both osteoporotic and clinical fractures. DISCUSSION: Existing data do not support the use of the more expensive denosumab as a first-line agent over bisphosphonates for reduction of fractures in postmenopausal women with osteoporosis. One limitation in this study was each RCT was not individually powered for fracture incidences.