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Out-of-hospital cardiac arrest is a leading cause of death worldwide. Establishing vascular access is critical for administering guideline-recommended drugs during cardiopulmonary resuscitation. Both the intraosseous route and the intravenous route are used routinely, but their comparative effectiveness remains unclear. We conducted a randomized clinical trial to compare the effectiveness of initial attempts at intraosseous or intravenous vascular access in adults who had nontraumatic out-of-hospital cardiac arrest. The primary outcome was a sustained return of spontaneous circulation. Key secondary outcomes were survival at 30 days and survival at 30 days with a favorable neurologic outcome, defined by a score of 0 to 3 on the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability). Among 1506 patients who underwent randomization, 1479 were included in the primary analysis (731 in the intraosseous-access group and 748 in the intravenous-access group). The successful establishment of vascular access within two attempts occurred in 669 patients (92%) assigned to the intraosseous-access group and in 595 patients (80%) assigned to the intravenous-access group. Sustained return of spontaneous circulation occurred in 221 patients (30%) in the intraosseous-access group and in 214 patients (29%) in the intravenous-access group (risk ratio, 1.06; 95% confidence interval [CI], 0.90 to 1.24; P = 0.49). At 30 days, 85 patients (12%) in the intraosseous-access group and 75 patients (10%) in the intravenous-access group were alive (risk ratio, 1.16; 95% CI, 0.87 to 1.56); a favorable neurologic outcome at 30 days occurred in 67 patients (9%) and 59 patients (8%), respectively (risk ratio, 1.16; 95% CI, 0.83 to 1.62). Prespecified adverse events were uncommon. There was no significant difference in sustained return of spontaneous circulation between initial intraosseous and intravenous vascular access in adults who had out-of-hospital cardiac arrest. (Funded by the Novo Nordisk Foundation and others; IVIO EU Clinical Trials Register number, 2022-500744-38-00; ClinicalTrials.gov number, NCT05205031.).

Get the support you need to safely extend dating of parenteral drugs beyond the usual 24-hour limit--minimizing waste, lowering medication costs, and enabling optimal patient administration schedules at alternate infusion sites. The new seventh edition features the inclusion of monographs expanded beyond home infusion to be inclusive of all clinical settings where parenteral drugs are stored or compounded.

Levodopa is the most effective therapy for Parkinson's disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube. In our 12-week, randomised, double-blind, double-dummy, double-titration trial, we enrolled adults (aged ≥30 years) with advanced Parkinson's disease and motor complications at 26 centres in Germany, New Zealand, and the USA. Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube, and were then randomly allocated (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo. Randomisation was stratified by site, with a mixed block size of 2 or 4. The primary endpoint was change from baseline to final visit in motor off-time. We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome. We assessed efficacy in a full-analysis set of participants with data for baseline and at least one post-baseline assessment, and imputed missing data with the last observation carried forward approach. We assessed safety in randomly allocated patients who underwent the percutaneous gastrojejunostomy procedure. This study is registered with ClinicalTrials.gov, numbers NCT00660387 and NCT0357994. From baseline to 12 weeks in the full-analysis set, mean off-time decreased by 4·04 h (SE 0·65) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2·14 h (0·66) for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference −1·91 h [95% CI −3·05 to −0·76]; p=0·0015). Mean on-time without troublesome dyskinesia increased by 4·11 h (SE 0·75) in the intestinal gel group and 2·24 h (0·76) in the immediate-release oral group (difference 1·86 [95% CI 0·56 to 3·17]; p=0·0059). In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (five [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (seven [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube. Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson's disease with motor complications. Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date, and our study is, to our knowledge, the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study. AbbVie.

Hereditary transthyretin amyloidosis is caused by the deposition of misfolded transthyretin proteins in peripheral nerves and other tissues. This phase 3 trial tested patisiran, a small interfering RNA targeting transthyretin messenger RNA, to treat the disease.

In this cluster-randomized, crossover trial, hospital-wide use of lactated Ringer’s solution as compared with normal saline did not alter the incidence of death or hospital readmission within 90 days.

Purpose To determine the effects of the sodium content of maintenance fluid therapy on cumulative fluid balance and electrolyte disorders. Methods We performed a randomized controlled trial of adults undergoing major thoracic surgery, randomly assigned (1:1) to receive maintenance fluids containing 154 mmol/L (Na154) or 54 mmol/L (Na54) of sodium from the start of surgery until their discharge from the ICU, the occurrence of a serious adverse event or the third postoperative day at the latest. Investigators, caregivers and patients were blinded to the treatment. Primary outcome was cumulative fluid balance. Electrolyte disturbances were assessed as secondary endpoints, different adverse events and physiological markers as safety and exploratory endpoints. Findings We randomly assigned 70 patients; primary outcome data were available for 33 and 34 patients in the Na54 and Na154 treatment arms, respectively. Estimated cumulative fluid balance at 72 h was 1369 mL (95% CI 601–2137) more positive in the Na154 arm ( p  < 0.001), despite comparable non-study fluid sources. Hyponatremia < 135 mmol/L was encountered in four patients (11.8%) under Na54 compared to none under Na154 ( p  = 0.04), but there was no significantly more hyponatremia < 130 mmol/L (1 versus 0; p  = 0.31). There was more hyperchloremia > 109 mmol/L under Na154 (24/35 patients, 68.6%) than under Na54 (4/34 patients, 11.8%) ( p  < 0.001). The treating clinicians discontinued the study due to clinical or radiographic fluid overload in six patients receiving Na154 compared to one patient under Na54 (excess risk 14.2%; 95% CI − 0.2–30.4%, p  = 0.05). Conclusions In adult surgical patients, sodium-rich maintenance solutions were associated with a more positive cumulative fluid balance and hyperchloremia; hypotonic fluids were associated with mild and asymptomatic hyponatremia.

In a trial involving adults with out-of-hospital cardiac arrest, an intraosseous-first strategy for vascular access did not result in a higher incidence of 30-day survival than an intravenous-first strategy.

Background Indications for intra-osseous (IO) infusion are increasing in adults requiring administration of fluids and medications during initial resuscitation. However, this route is rarely used nowadays due to a lack of knowlegde and training. We reviewed the current evidence for its use in adults requiring resuscitative procedures, the contraindications of the technique, and modalities for catheter implementation and skill acquisition. Methods A PubMed search for all articles published up to December 2015 was performed by using the terms “Intra-osseous” AND “Adult”. Additional articles were included by using the “related citations” feature of PubMed or checking references of selected articles. Editorials, comments and case reports were excluded. Abstracts of all the articles that the search yielded were independently screened for eligibility by two authors and included in the analysis after mutual consensus. In total, 84 full-text articles were reviewed and 49 of these were useful for answering the following question “when, how, and for which population should an IO infusion be used in adults” were selected to prepare independent drafts. Once this step had been completed, all authors met, reviewed the drafts together, resolved disagreements by consensus with all the authors, and decided on the final version. Results IO infusion should be implemented in all critical situations when peripheral venous access is not easily obtainable. Contraindications are few and complications are uncommon, most of the time bound to prolonged use. The IO infusion allows for blood sampling and administration of virtually all types of fluids and medications including vasopressors, with a bioavailability close to the intravenous route. Unfortunately, IO infusion remains underused in adults even though learning the technique is rapid and easy. Conclusions Indications for IO infusion use in adults requiring urgent parenteral access and having difficult intravenous access are increasing. Physicians working in emergency departments or intensive care units should learn the procedures for catheter insertion and maintenance, the contraindications of the technique, and the possibilities this access offers.

In-line filtration is increasingly used in critically-ill infants but its benefits, by preventing micro-particle infusion in very preterm neonates, remain to be demonstrated. We conducted a randomized controlled trial among very preterm infants allocated to receive either in-line filtration of all the intra-venous lines or standard care without filters. The primary outcome was differences greater than 20% in the median changes in pro-inflammatory cytokine serum concentrations measured at day 3 and day 8 (+/−1) using a Luminex multianalytic profiling technique. Major neonatal complications were analyzed as secondary predefined outcomes. We randomized 146 infants, assigned to filter (n = 73) or control (n = 73) group. Difference over 20% in pro-inflammatory cytokine concentration between day 3 and day 8 was not found statistically different between the two groups, both in intent-to-treat (with imputation) and per protocol (without imputation) analyses. The incidences of most of neonatal complications were found to be similar. Hence, this trial did not evidence a beneficial effect of in-line filtration in very preterm infants on the inflammatory response syndrome and neonatal morbidities. These data should be interpreted according to local standards in infusion preparation and central line management.

Background Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. Methods This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4–12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone. Discussion If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival. Trial registration The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.