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BACKGROUND: Complex regional pain syndrome (CRPS) is a debilitating and painful condition accompanied by sensory, autonomic, trophic, and/or motor abnormalities. Although CRPS is rare in the general population, the prevalence among individuals at higher risk, particularly posttraumatic and postsurgical patients, remains unknown. This study aims to provide a benchmark that quantifies CRPS prevalence in high-risk groups, and offers insights on potential predictors of developing CRPS. METHODS: We conducted a systematic review and meta-analysis to identify studies reporting prevalence of CRPS after an inciting event (eg, fracture, surgery), specifically 12-month and 24-month prevalence (primary outcomes), as well as 3-month and 6-month prevalence (secondary outcomes). Estimates from individual studies were transformed using double-arcsine transformation, and the resulting estimates with 95% confidence interval (CI) were pooled in a meta-analysis using a random-effects model. RESULTS: We included 214 articles with data from 2491,378 participants worldwide (35 countries), of which 16,873 had CRPS. The pooled 12-month and 24-month global prevalence was 3.04% (95% CI, 2.64–3.48) and 6.46% (95% CI, 5.46–7.53), respectively. Subgroup analysis and meta-regression were performed to understand the impact of population-dependent (mechanism of injury, type of CRPS), contextual-dependent (socioeconomic status), and methodological-dependent (study design, publication year) factors. The 12-month prevalence was higher in countries with a high human development index (HDI) compared to those with a medium or very high HDI, was higher in participants with a traumatic inciting injury only versus those with surgical injury only or traumatic/surgical injury, and was higher in prospective versus retrospective studies. Meta-regression analysis showed that publication year was a significant moderator, with more recent articles reporting lower 12-month prevalence. CONCLUSIONS: This study provides a benchmark of the global prevalence of CRPS, which anesthesiologists and pain specialists can use to prioritize early diagnosis and identify those at the highest risk for CRPS.

AbstractBackgroundAcute lymphoblastic leukemia (ALL) in adults is aggressive, with long‐term outcomes impacted by treatment resistance and toxicity. CD52 is expressed in most cases of B‐ and T‐lineage ALL. Alemtuzumab, a humanized immunoglobulin G1 monoclonal antibody that targets CD52, was identified as a potential agent to improve treatment efficacy without increasing toxicity.MethodsIn this phase 1/2 study (Cancer and Leukemia Group B [CALGB] 10102, NCT00061945), a course of single‐agent alemtuzumab was intercalated into CALGB 19802 backbone chemotherapy after the third course of intensive chemotherapy in those who were CD52+ at diagnosis. Phase 1 tested three dose levels of subcutaneous alemtuzumab (10, 20, and 30 mg 3 times weekly for 4 weeks/12 doses) and demonstrated that 30 mg was tolerable. Phase 2 established feasibility.ResultsThe study enrolled 295 evaluable patients (115 in phase 1, 180 in phase 2); 206 (69.8%) were CD52+. Among evaluable CD52+ patients, 43.7% (90/206) completed the first three treatment modules; 97.8% (88 of 90) were treated with alemtuzumab. Alemtuzumab was associated with cytomegalovirus viremia, which occurred in 23.3% (14 of 60) of patients during and 29.2% (19 of 65) after alemtuzumab treatment. With a median follow‐up of 101.2 months, median overall survival (OS) was 26.3 months (3‐year rate, 44%; 5‐year rate, 36%; 10‐year rate, 31%). Landmark analysis at the start of the fourth course of treatment demonstrated no difference in OS or disease‐free survival between patients who did and who did not receive alemtuzumab.ConclusionAlemtuzumab was feasible to administer in adults with ALL receiving intensive chemotherapy, but was without evidence of benefit.

INTRODUCTION: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aim of this study was to characterize the utilization of opioids and associations with clinical characteristics in adult patients with CP. METHODS: This cross-sectional analysis used baseline data from participants with definite CP enrolled in a cohort study in the United States (PROspective Evaluation of CP for EpidEmiologic and Translational StuDies). Data on demographics, pain medication use, healthcare utilization, disability, and pain patterns were systematically collected in case report forms while quality of life was assessed with patient-reported outcome instruments. Opioid use was classified according to strength (weak or strong) and frequency (scheduled or as-needed). RESULTS: A total of 681 participants (n = 364, 53% male) were included: 299 (44%) were current opioid users (22% only weak opioids and 22% at least 1 strong opioid). Increasing frequency and severity of pain was associated with increase of weak, strong, as-needed, or scheduled opioids. Neuromodulators were used by ∼40% of participants; increasing use was associated with increasing frequency and severity of pain. On multivariate analysis, independent predictors associated with strength and frequency of current opioid use were pain patterns (odds ratios [ORs] 1.84–8.32 and ORs 1.92–8.52, respectively, P < 0.001) and prior celiac plexus block (OR 3.54, 95% confidence intervals 1.82–6.87 and OR 3.42, 95% confidence intervals 1.76–6.64, respectively). Participants using opioids had higher prevalence of disability, healthcare utilization, and poorer quality of life. DISCUSSION: Opioid use in CP is common and associated with increased pain severity and constancy. These data provide foundational estimates for future trials that can elucidate the complex interactions between patient factors, pain, and interventions.

Background Our study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC. Methods This is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received two doses of 200 mg pembrolizumab, surgery, standard adjuvant chemotherapy, followed by four doses adjuvant pembrolizumab. The primary objective of this study was to determine surgical feasibility rate, and secondary objectives are pathological response rate, treatment adverse events, efficacy data, and exploratory analysis of biomarkers. Results 30 patients initiated perioperative pembrolizumab, and 25 completed tumor resection. At median follow-up of 59 months after surgical resection, seven patients had disease progression, while six had died representing. A 5-year progression-free survival (PFS) from time of surgery was 72.0% (56.4%–91.9%) and overall survival (OS) from time of surgery was 75.8% (60.7%–94.7%). Major pathological response (MPR) was found in seven tumors (28%) including two complete responses (4%). Across all treated patients, four receiving neoadjuvant and four receiving adjuvant pembrolizumab experienced treatment-related adverse events of grade 3 or higher with no grade 5 events. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased across our patient cohort over time from baseline until postsurgery and remained elevated at the end of treatment. There was a significant difference between mean plasma PCSK9 levels for patients with MPR versus all other patients on study when checked postoperatively. Conclusions Perioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS.

Summary: The development of clinical practice guidelines is an evolving field. In response to the need for consistent, evidence-based medical practice, the American Clinical Neurophysiology Society identified the need to update the Society's guideline development process. The American Clinical Neurophysiology Society Guidelines Committee created an action plan with the goal of improving transparency and rigor for future guidelines and bringing existing guidelines to current standards. This article provides an overview of the new American Clinical Neurophysiology Society standards for the creation of clinical guidance documents, including clinical guidelines, technical standards, and consensus statements. This process is rooted in the importance of clinical guidance documents and their significance in the context of current behests for updated standards for practicing clinical neurophysiology. The need and rationale for updating the guideline development process from its prior state were described. The updated American Clinical Neurophysiology Society categories for clinical guidance and recommendations were defined and compared. Finally, the new process is summarized, focusing on methodologies, authorship, and conflicts of interest.

Background: It is known that there are discrepancies between insurance status and access to care for a variety of health conditions. In addition, differences have been shown in initial in-hospital management of stroke as well as outcomes in the acute setting. We sought to examine the relationship between insurance status and risk of recurrent stroke, major bleeding or death following an incident cryptogenic stroke. Methods: Patients with cryptogenic stroke included in a multicenter (n=27 sites) retrospective observational cohort and complete insurance status were evaluated for a primary composite outcome of recurrent stroke, major bleeding, or death. Insurance providers were categorized by Private/Veterans Administration, Medicare, Other, and Medicaid/pending/None, with the primary carrier ranked in that order when multiple insurance carriers applied. Descriptive statistics and an adjusted Cox proportional hazards regression were used to associate the primary insurance provider with the composite outcome, and with each unique secondary outcome, adjusting for age, stroke severity, pre-stroke disability, atherosclerotic risk factors, and potential embolic sources (e.g., patent foramen ovale). Results: Of the 2201 patients, 2006 (91.1%) had reported insurance information and were followed for a median of 1.50 years (interquartile range [IQR 0.41 - 2.99y]). The majority of patients were primary Medicare beneficiaries (42.3%), followed by private insurance (36.7%), Medicaid/none (18.1%) and Other (2.9%). Although there were important differences in demographic and neurodiagnostic results across insurance groups, compared to Private/VA beneficiaries, beneficiaries for Medicaid/pending/none had a higher rate of the composite outcome in adjusted regression (adjusted hazard ratio [HR] 1.35, 95% confidence interval [CI], 1.07-1.69) which was driven largely by the higher rate of recurrent stroke (adjusted HR 1.33, 95%CI, 1.02-1.73) with no significant difference in rate of major bleeding or death (p>0.05 for both). Conclusions: Independent of age, race, pre-existing disability, and atherosclerotic risk factors, insurance status was independently predictive of recurrent stroke in this diverse cohort of cryptogenic stroke.