Peripheral nerve blocks (PNBs) are increasingly used as a component of multimodal analgesia and may be administered as a single injection (sPNB) or continuous infusion via a perineural catheter (cPNB). We undertook a qualitative review focusing on sPNB and cPNB with regard to benefits, risks, and opportunities for optimizing patient care. Meta-analyses of randomized controlled trials have shown superior pain control and reductions in opioid consumption in patients receiving PNB compared with those receiving intravenous opioids in a variety of upper and lower extremity surgical procedures. cPNB has also been associated with a reduction in time to discharge readiness compared with sPNB. Risks of PNB, regardless of technique or block location, include vascular puncture and bleeding, nerve damage, and local anesthetic systemic toxicity. Site-specific complications include quadriceps weakness in patients receiving femoral nerve block, and pleural puncture or neuraxial blockade in patients receiving interscalene block. The major limitation of sPNB is the short (12-24 hours) duration of action. cPNB may be complicated by catheter obstruction, migration, and leakage of local anesthetic as well as accidental removal of catheters. Potential infectious complications of catheters, although rare, include local inflammation and infection. Other considerations for ambulatory cPNB include appropriate patient selection, education, and need for 24/7 availability of a health care provider to address any complications. The ideal PNB technique would have a duration of action that is sufficiently long to address the most intense period of postsurgical pain; should be associated with minimal risk of infection, neurologic complications, bleeding, and local anesthetic systemic toxicity; and should be easy to perform, convenient for patients, and easy to manage in the postoperative period.

To evaluate the use of lipid emulsion for reversal of local anesthetic-induced toxicity. Literature was accessed through PubMed and OVID (1966-May 2007) using the search terms lipid emulsion and local anesthetic. Reference lists were consulted to identify additional publications. All articles published in English were evaluated for inclusion. Publications describing the use of lipid emulsion for reversal of local anesthetic in either humans or animals were included. It has been suggested that lipid emulsion (Intralipid) may reverse local anesthetic toxicity by extracting lipophilic local anesthetics from aqueous plasma or tissues or by counteracting local anesthetic inhibition of myocardial fatty acid oxygenation. Studies in rats and dogs have shown that lipid emulsion is effective in resuscitating animals who are asystolic after the administration of intravenous bupivacaine. Three case reports support the use of lipid emulsion to reverse systemic toxicity, including seizures, electrocardiogram abnormalities, and cardiac arrest, resulting from the administration of levobupivacaine, ropivacaine, bupivacaine, or mepivacaine. The regimens used in these cases consisted of bolus doses of 1.2-2 mL/kg followed by continuous infusions of 0.25-0.5 mL/kg/min. All of the patients recovered fully with no neurologic sequelae. Literature describing animal studies and human case reports suggests that lipid emulsion is effective in the reversal of local anesthetic toxicity. The potential risks of administering the relatively high doses of this agent are uncertain, and the optimal dose has not been established. In light of these uncertainties, it is appropriate to administer lipid emulsion only after advanced cardiac life support has failed and prior to cardiopulmonary bypass.

Summary: Background: Hepatorenal syndrome and acute kidney injury are common complications of decompensated cirrhosis, and terlipressin is recommended as first‐line vasoconstrictor therapy. However, data on its use outside of clinical trials are lacking.Aims: To assess practice patterns and outcomes around vasoconstrictor use for hepatorenal syndrome in UK hospitals.Methods: This was a multicentre chart review study. Data were extracted from medical records of patients diagnosed with hepatorenal syndrome and treated by vasoconstrictor drugs between January 2013 and December 2017 at 26 hospitals in the United Kingdom. The primary outcome was improvement of kidney function, defined as complete response (serum creatinine improved to ≤1.5 mg/dL), partial response (serum creatinine reduction of ≥20% but >1.5 mg/dL) and overall response (complete or partial response). Other outcomes included need for dialysis, mortality, liver transplantation and adverse events.Results: Of the 225 patients included in the analysis, 203 (90%) were treated with terlipressin (median duration, 6 days; range: 2‐24 days). Mean (±standard deviation) serum creatinine at vasopressor initiation was 3.25 ± 1.64 mg/dL. Terlipressin overall response rate was 73%. Overall response was higher in patients with mild acute kidney injury (baseline serum creatinine <2.25 mg/dL), compared to those with moderate (serum creatinine ≥2.25 mg/dL and <3.5 mg/dL) or severe (serum creatinine ≥3.5 mg/dL). Ninety‐day survival was 86% for all patients (93% for overall responders vs 66% for treatment nonresponders, P < 0.0001).Conclusion: Terlipressin is the most commonly prescribed vasoconstrictor for patients with hepatorenal syndrome in the United Kingdom. Treatment with terlipressin in patients with less severe acute kidney injury (serum creatinine <2.25 mg/dL) was associated with higher treatment responses, and 90‐day survival.

Patient-related (demographic/disease) and treatment-related (drug/clinician/hospital) characteristics were evaluated as potential predictors of healthcare resource use and opportunities for early switch (ES) from intravenous (IV)-to-oral methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotic therapy and early hospital discharge (ED). This retrospective observational medical chart study analyzed patients (across 12 European countries) with microbiologically confirmed MRSA complicated skin and soft tissue infections (cSSTI), ≥3 days of IV anti-MRSA antibiotics during hospitalization (July 1, 2010-June 30, 2011), and discharged alive by July 31, 2011. Logistic/linear regression models evaluated characteristics potentially associated with actual resource use (length of IV therapy, length of hospital stay [LOS], IV-to-oral antibiotic switch), and ES and ED (using literature-based and expert-verified criteria) outcomes. 1542 patients (mean ± SD age 60.8 ± 16.5 years; 61.5% males) were assessed with 81.0% hospitalized for MRSA cSSTI as the primary reason. Several patient demographic, infection, complication, treatment, and hospital characteristics were predictive of length of IV therapy, LOS, IV-to-oral antibiotic switch, or ES and ED opportunities. Outcomes and ES and ED opportunities varied across countries. Length of IV therapy and LOS (r = 0.66, p < 0.0001) and eligibilities for ES and ED (r = 0.44, p < 0.0001) showed relatively strong correlations. IV-to-oral antibiotic switch patients had significantly shorter length of IV therapy (−5.19 days, p < 0.001) and non-significantly shorter LOS (−1.86 days, p > 0.05). Certain patient and treatment characteristics were associated with increased odds of ES (healthcare-associated/ hospital-acquired infection) and ED (patient living arrangements, healthcare-associated/ hospital-acquired infection, initiating MRSA-active treatment 1–2 days post cSSTI index date, existing ED protocol), while other factors decreased the odds of ES (no documented MRSA culture, ≥4 days from admission to cSSTI index date, IV-to-oral switch, IV line infection) and ED (dementia, no documented MRSA culture, initiating MRSA-active treatment ≥3 days post cSSTI index date, existing ES protocol). Practice patterns and opportunity for further ES and ED were affected by several infection, treatment, hospital, and geographical characteristics, which should be considered in identifying ES and ED opportunities and designing interventions for MRSA cSSTI to reduce IV days and LOS while maintaining the quality of care.

Recent data suggest significant underutilization of hypomethylating agents (HMAs) that are recommended treatments for patients with myelodysplastic syndromes (MDS) with refractory anemia with excess blasts (RAEB). The study objective was to assess the degree of HMA use and predictors of HMA underuse in this population. This was a retrospective study including patients diagnosed with the RAEB form of MDS between January 2011 and December 2015 using the Surveillance, Epidemiology, and End Results-Medicare linked database. Patients were excluded if they had < 1 year of continuous enrollment before diagnosis or received stem cell transplant or lenalidomide during the follow-up period. HMA non-peristence was defined as use of < 4 cycles (3-10 HMA days/28 days) of HMAs or a gap of ≥ 90 days between consecutive cycles. Patients were characterized as HMA never-users, HMA-persistent users, and HMA-non-persistent users. Descriptive statistics were used to summarize patient characteristics. Multivariable logistic regression was used to assess predictors of HMA underuse and persistence. Of the 1190 patients, 526 (44%) were never-users, 295 (25%) were non-persistent users, and 369 (31%) were persistent users. Age at diagnosis (eg, 66-70 years vs. ≥ 80 years; odds ratio [OR], 2.36; 95% confidence interval [CI], 1.56-3.56), marital status (single vs. married; OR, 0.67; 95% CI, 0.51-0.89), National Cancer Institute comorbidity index (≥ 3 vs. 0-1; OR, 0.62; 95% CI, 0.46-0.83), and performance status (poor vs. good; OR, 0.67; 95% CI, 0.51-0.87) were significantly associated with HMA underuse. Several demographic and clinical factors were associated with underuse of HMAs. There is need for a better understanding of suboptimal HMA use and its relationship with clinical response.

Microsatellite instability-high (MSI-H) and deficient DNA mismatch repair (dMMR) status have emerged as actionable biomarkers for advanced endometrial cancer (aEC). The objective of this study was to assess clinical outcomes and treatment patterns among MSI-H/dMMR aEC patients who had disease progression following prior systemic therapy (FPST) in the US. Endometrial Cancer Health Outcomes (ECHO) was a retrospective, medical chart review study of patients with MSI-H/dMMR aEC who had disease progression between 07/01/2016 and 12/31/2018 FPST and were not candidates for curative surgery. Data on patient demographics, clinical and treatment characteristics, and clinical outcomes were collected. Kaplan-Meier analyses were performed to estimate real-world progression-free survival (rwPFS) and overall survival (OS), stratified by drug class. A total of 124 eligible patients who initiated second-line chemotherapy ± bevacizumab or immunotherapy were included. Mean age was 61.4 years at aEC diagnosis and 86.3% of patients were stage IIIB-IV. Median rwPFS and OS were 4.0 months (95% CI: 2.0-9.0) and 7.0 months (95% CI: 5.0-18.0), respectively, among 21 patients who received chemotherapy ± bevacizumab, and 29.0 months (95% CI: 18.0-NE) and not reached (95% CI: 30.0-NA), respectively, among 103 patients who received immunotherapy. Most patients (n = 92) received pembrolizumab; among these patients, rwPFS and OS were 29.0 months (95% CI: 18.0-NE) and 30 months (95% CI: 30.0-NA), respectively. Real-world evidence suggests that pembrolizumab monotherapy provides considerable clinical benefits and has become the standard of care for MSI-H/dMMR aEC patients FPST who are not candidates for curative surgery in real-world settings.