Blood pressure elevation in erenumab-treated patients with migraine: A retrospective real-world experience.

BACKGROUND: Erenumab is a monoclonal antibody that targets the calcitonin gene-related peptide (CGRP) receptor and is approved for the preventative treatment of migraine in adults. CGRP is involved in the regulation of vasomotor tone under physiologic and pathologic conditions, including hypertension. While there has not been evidence of hypertension in preclinical models or clinical trials, post-marketing data suggest erenumab may be associated with hypertension. This led to a warning in the United States Food and Drug Administration prescribing information for erenumab. OBJECTIVE: To determine the frequency of worsening blood pressure (BP) after initiation of erenumab in patients with migraine and how this is associated with hypertension. METHODS: This is an observational retrospective cohort study evaluating patients at a tertiary headache or neurology department. Systolic and diastolic BPs were compared between the initial visit prior to initiation of erenumab, and follow-up visit while on erenumab. Worsening BP was defined as moving from a lower stage to a higher stage of BP, as defined by the American Heart Association. Serious adverse vascular events were also recorded. RESULTS: A total of 335 patients were included in the final analysis (mean [SD] age of 45.7 [14.40] years, 83.9% [281/335] female). At baseline, 20.9% (70/335) of patients had a prior diagnosis of hypertension. The median (interquartile range) time to follow-up appointment from initial appointment was 20.5 (13.3-35.3) weeks. The mean (SD) BP at baseline was systolic 124.7 (15) mmHg and diastolic 77 (11) mmHg, and at follow-up was systolic 124.0 (15) mmHg and diastolic 77.8 (9) mmHg. Overall, 23.3% (78/335) of all patients had worsening BP, whereas 13/225 (3.9%) patients had improvement in their BP. Patients with atrial fibrillation were more likely to develop worsening BP (odds ratio, 4.9, 95% confidence interval 1.12-21.4; p = 0.035). There was no association between worsening BP and pre-existing hypertension, sex, body mass index, or age. One patient had non-ST elevation myocardial infarction attributed to a hypertensive emergency while on erenumab. CONCLUSION: We found that 23.3% of patients initiated on erenumab may have developed worsening BP, suggesting the need for BP monitoring in patients initiated on erenumab.

Evaluating the Need for Simultaneous Carpal Tunnel Release With Forearm Fasciotomy.

PURPOSE: The need to include simultaneous carpal tunnel release (sCTR) with forearm fasciotomy for acute compartment syndrome (ACS) or after vascular repair is unclear. We hypothesized that sCTR is more common when: 1) fasciotomies are performed by orthopedic or plastic surgeons, rather than general or vascular surgeons; 2) ACS occurred because of crush, blunt trauma, or fractures rather than vascular/reperfusion injuries; 3) elevated compartment pressures were documented. We also sought to determine the incidence of delayed CTR when not performed simultaneously. METHODS: Retrospective chart review identified patients who underwent forearm fasciotomy for ACS or vascular injury over a period of 10 years. Patient demographics, mechanism of ACS or indication for fasciotomy, surgeon subspecialty, compartment pressure measurements, inclusion of sCTR, complications, reoperations, and timing and method of definitive closure were analyzed. Logistic regression modeling was used to analyze predictors associated with delayed CTR. RESULTS: Fasciotomies were performed in 166 patients by orthopedic (63%), plastic (28%), and general/vascular (9%) surgeons. Orthopedic and plastic surgeons more frequently performed sCTR (67% and 63%, respectively). A total of 107 (65%) patients had sCTR. Fasciotomies for vascular/reperfusion injury were more likely to include sCTR (44%) compared with other mechanisms. If not performed simultaneously, 11 (19%) required delayed CTR at a median of 42 days. ACS secondary to fracture had the highest rate of delayed CTR (35%), and the necessity of late CTR for fractures was not supported by the logistic regression model. Residual hand paresthesias were less frequent in the sCTR group (6.5% vs 20%). Overall complication rates were similar in both groups (63% sCTR vs 70% without sCTR). CONCLUSION: When sCTR is excluded during forearm fasciotomy, 19% of patients required delayed CTR. This rate was higher (35%) when ACS was associated with fractures. Simultaneous CTR with forearm fasciotomy may decrease the incidence of residual hand paresthesias and the need for a delayed CTR. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognosis IV.

Stereotactic Body Proton Therapy Versus Conventionally Fractionated Proton Therapy for Early Prostate Cancer: A Randomized, Controlled, Phase 3 Trial.

PURPOSE: We aimed to determine if ultra-hypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is non-inferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. MATERIALS AND METHODS: This study was a multicenter, randomized, controlled, non-inferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, PSA <10 ng/mL, and clinical stage T1-2a N0 M0 according to AJCC 7th ed. Eligible participants were randomly assigned initially at a 1:1 ratio and later at a 2:1 ratio to SBPT (38 Gy in 5 fractions) or CFPT (79.2 Gy in 44 fractions). The primary endpoint was freedom from failure (FFF) at 2 years from the date of randomization. Non-inferiority for FFF was determined based on one-sided confidence intervals. Toxicities were compared at different time points using Fisher's Exact test. Health-related quality-of-life (HRQoL) was analyzed at different time points using a mixed-effects linear model. This trial is registered with ClinicalTrials.gov, NCT01230866, and is closed to accrual. RESULTS: Between December 10, 2010, and September 29, 2020, 144 patients were enrolled and 135 were randomly assigned (90 to the SBPT group and 45 to the CFPT group). The median follow-up was 5 years (IQR 3.9-5.2). The 2-year FFF was 100% for both groups, with the one-sided 5-year risk difference in FFF between groups reported as 2.63% (90% CI: -1.70%-6.96%), favoring the SBRT arm, thus fulfilling the pre-specified criteria for non-inferiority of SBPT compared to CFPT. Rates of gastrointestinal (GI) and genitourinary (GU) G2 and G3 toxicities did not differ significantly between groups but the the study was not powered to detect significant toxicity differences. Also, HRQoL metrics did not differ significantly between groups over the study median follow up. CONCLUSIONS: SBPT is non-inferior to CFPT regarding FFF, with similar long-term GU and GI toxicity rates and minimal impact in patient reported HRQoL over time.

No difference in COVID-19 treatment outcomes among current methamphetamine, cannabis and alcohol users.

BACKGROUND: Poor outcomes of COVID-19 have been reported in older males with medical comorbidities including substance use disorder. However, it is unknown whether there is a difference in COVID-19 treatment outcomes between patients who are current cannabis users, excessive alcohol drinkers and those who use a known hazardous stimulant such as methamphetamine (METH). METHODS: Electronic medical records (EMR) of COVID-19 patients with current METH (n = 32), cannabis (n = 46), and heavy alcohol use (n = 44) were reviewed. COVID-19 infection was confirmed by positive SARS-CoV-2 PCR test, current drug use was confirmed by positive urine drug testing, and alcohol use was identified by a blood alcohol concentration greater than 11 mg/dl. Multivariate linear regression models as well as the firth logistic regression models were used to examine the effect of substance use group (METH, cannabis, or alcohol) on treatment outcome measures. RESULTS: A total of 122 patients were included in this analysis. There were no significant differences found between drug groups in regards to key SARS-CoV-2 outcomes of interest including ICU admission, length of stay, interval between SARS-CoV-2 positive test and hospital discharge, delirium, intubation and mortality after adjusting for covariates. About one-fifth (21.9% in METH users, 15.2% in cannabis users, and 20.5% in alcohol users) of all patients required ICU admission. As many as 37.5% of METH users, 23.9% of cannabis users, and 29.5% of alcohol users developed delirium (P = 0.4). There were no significant differences between drug groups in COVID-19 specific medication requirements. Eight patients in total died within 10 months of positive SARS-CoV-2 PCR test. Two patients from the METH group (6.3%), two patients from the cannabis group (4.3%), and four patients from the alcohol group (9.1%) died. DISCUSSION: The study outcomes may have been affected by several limitations. These included the methodology of its retrospective design, relatively small sample size, and the absence of a COVID-19 negative control group. In addition, there was no quantification of substance use and many covariates relied on clinical documentation or patient self-report. Finally, it was difficult to control for all potential confounders particularly given the small sample size. CONCLUSION: Despite these limitations, our results show that current METH, cannabis, and heavy alcohol users in this study have similar treatment outcomes and suffer from high morbidity including in-hospital delirium and high mortality rates within the first-year post COVID-19. The extent to which co-morbid tobacco smoking contributed to the negative outcomes in METH, cannabis, and alcohol users remains to be investigated.