Robotic Versus Open Hepatic Arterial Infusion Pump Placement for Unresectable Intrahepatic Cholangiocarcinoma.

BACKGROUND: Hepatic arterial infusion pump (HAIP) chemotherapy is an effective treatment for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). HAIP chemotherapy requires a catheter inserted in the gastroduodenal artery and a subcutaneous pump. The catheter can be placed using an open or robotic approach. OBJECTIVE: This study aimed to compare perioperative outcomes of robotic versus open HAIP placement in patients with unresectable iCCA. METHODS: We analyzed patients with unresectable iCCA included in the PUMP-II trial from January 2020 to September 2022 undergoing robotic or open HAIP placement at Amsterdam UMC, Erasmus MC, and UMC Utrecht. The primary outcome was time to functional recovery (TTFR). RESULTS: In total, 22 robotic and 28 open HAIP placements were performed. The median TTFR was 2 days after robotic placement versus 5 days after open HAIP placement (p < 0.001). One patient (4.5%) in the robotic group underwent a conversion to open because of a large bulky tumor leaning on the hilum immobilizing the liver. Postoperative complications were similar-36% (8/22) after robotic placement versus 39% (11/28) after open placement (p = 1.000). The median length of hospital stay was shorter in the robotic group-3 versus 5 days (p < 0.001). All 22 robotic patients initiated HAIP chemotherapy post-surgery, i.e. 93% (26/28) in the open group (p = 0.497). The median time to start HAIP chemotherapy was 14 versus 18 days (p = 0.153). CONCLUSION: Robotic HAIP placement in patients with unresectable iCCA is a safe and effective procedure and is associated with a significantly shorter TTFR and hospital stay than open HAIP placement.

Safety and Efficacy of High-Dose Memory CD45RO+ Donor Lymphocyte Infusion in Pediatric Recipients after Hematopoietic Stem Cell Transplantation.

Memory T selected cells (CD45RA-/RO+) as donor lymphocyte infusion are less capable of producing alloreactivity and graft versus host disease (GvHD) compared with naïve T cells. The objective of this study was to evaluate the safety and efficacy of high-dose memory (CD45RA-/RO+) donor lymphocyte infusion (mDLI) after allogeneic hematopoietic cell transplantation (HCT). Indications for mDLI were "as needed" and "as prophylactic regimen." Sixty-one children diagnosed with malignant (82%) and non-malignant diseases (18%) received 241 mDLIs. Patients received a median of three infusions (range 1‒13) of mDLI with a median infused dose of 1.35 × 107/kg CD45RO+ containing 8.96 × 106/kg CD3+CD45RO+ and 3.81 × 103/kg CD3+CD45RA+. De novo GvHD developed in 7 patients following 4% of the mDLI infusions. Among patients with GvHD before mDLI, this condition worsened following 6 infusions (11%) in the 3 patients with grade II-IV acute GvHD. A decrease in cytomegalovirus viral load followed 65% of mDLI infusions. Two-year overall survival (OS) for the total cohort was 64% (95% CI 57%‒72%). For patients receiving prophylactic mDLI, the two-year non-relapse mortality was 10% (95% CI 9%‒11%). In summary, high-dose mDLI is feasible and safe, with a relatively low risk of severe GvHD even in patients with active GvHD. Importantly, mDLI was associated with positive effects, including enhanced control of CMV viremia.

Delphi Process for Validation of Fluid Treatment Algorithm for Critically Ill Pediatric Trauma Patients.

INTRODUCTION: While intravenous fluid therapy is essential to re-establishing volume status in children who have experienced trauma, aggressive resuscitation can lead to various complications. There remains a lack of consensus on whether pediatric trauma patients will benefit from a liberal or restrictive crystalloid resuscitation approach and how to optimally identify and transition between fluid phases. METHODS: A panel was comprised of physicians with expertise in pediatric trauma, critical care, and emergency medicine. A three-round Delphi process was conducted via an online survey, with each round being followed by a live video conference. Experts agreed or disagreed with each aspect of the proposed fluid management algorithm on a five-level Likert scale. The group opinion level defined an algorithm parameter's acceptance or rejection with greater than 75% agreement resulting in acceptance and greater than 50% disagreement resulting in rejection. The remaining were discussed and re-presented in the next round. RESULTS: Fourteen experts from five Level 1 pediatric trauma centers representing three subspecialties were included. Responses were received from 13/14 participants (93%). In round 1, 64% of the parameters were accepted, while the remaining 36% were discussed and re-presented. In round 2, 90% of the parameters were accepted. Following round 3, there was 100% acceptance by all the experts on the revised and final version of the algorithm. CONCLUSIONS: We present a validated algorithm for intavenous fluid management in pediatric trauma patients that focuses on the de-escalation of fluids. Focusing on this time point of fluid therapy will help minimize iatrogenic complications of crystalloid fluids within this patient population.

Safety and Effectiveness of a Standardized Intravenous Insulin Infusion Order Set for Managing Uncontrolled Hyperglycemia Outside the Intensive Care Unit.

BACKGROUND: Few studies have evaluated the administration of intravenous (IV) insulin infusions for uncontrolled hyperglycemia in non-intensive care unit (ICU) patients, and there is inadequate data to guide how to appropriately administer IV insulin infusions to this patient population. OBJECTIVE: Determine the effectiveness and safety of our institution's non-critical care IV insulin infusion order set. METHODS: This retrospective study was conducted at 2 institutions within a health care system. The primary outcome was the number of individuals who achieved a glucose level ≤180 mg/dL. For those meeting this endpoint, the time to achieving this outcome and the percentage of glucose checks within the goal range were determined. The primary safety endpoint was the number of individuals who experienced hypoglycemia (glucose level <70 mg/dL). Patients were included if they were ≥18 years of age and received the non-critical care IV insulin infusion order set outside of the ICU. RESULTS: Twenty-one (84%) patients achieved a glucose level ≤180 mg/dL. The median (inter-quartile range [IQR]) time to achieving the primary outcome was 5.7 h (3.9-8.3). In patients who achieved the primary outcome, 41.8% of the glucose readings obtained after achieving this outcome were within goal range. Two (8%) patients experienced hypoglycemia. Both of these events occurred within 8 hours of therapy initiation and neither patient received prior doses of subcutaneous insulin. Of the 4 patients who did not achieve a glucose level ≤180 mg/dL, 2 received high-dose corticosteroids, and 3 achieved a glucose level between 181 and 200 mg/dL. CONCLUSION AND RELEVANCE: Our findings support the safe administration of IV insulin infusions to non-ICU patients when targeting a glucose range of 140 to 180 mg/dL and limiting the infusion duration.

Transitioning patients from intravenous to subcutaneous infliximab and vedolizumab for inflammatory bowel disease: what is the opportunity cost of improving access to healthcare?

BACKGROUND: Biologic drugs are highly effective for inflammatory bowel disease (IBD) management but are key drivers of costs of care especially when administered intravenously (i.v.). Availability of subcutaneous (SC) formulations has increased convenience for patients and improved access to care, but at the cost of revenue to health services. AIMS: To evaluate the economic impact of transitioning a tertiary centre IBD cohort from i.v. to SC biologic administration and assess the implications for key stakeholders. METHODS: A retrospective analysis of all patients who received i.v. infliximab or vedolizumab in the outpatient infusion centre of a tertiary IBD centre between July 2019 and June 2021 was undertaken. Data were collated from electronic medical records, pharmacy dispensing systems and the hospital business intelligence unit. An economic analysis and theoretical financial/capacity impact analysis of a transition to an SC model were estimated under two scenarios using a random 10% and 30% of the patient cohort. RESULTS: Transitioning our IBD cohort from i.v. to SC administration would result in a loss to our health service of AU$2 732 123.75, composed of AU$1 463 003.75 in Weighted Inlier Equivalent Separation (WIES) and AU$1 269 120 in drug procurement revenue. However, it would ease capacity in the infusion centre by up to 5256 h. CONCLUSIONS: Transitioning patients to SC administration results in improved access to infusion centres and substantial savings to state governments; however, switching results in a loss of i.v. biologic-generated WIES to health services. Alternative funding models are required to achieve sustainability in IBD care and reduce reliance on i.v. biologic-generated income.

Rechallenges without desensitization following platinum-based chemotherapy reactions.

BACKGROUND: There is increasing interest in non-desensitization protocols as a potential way to reintroduce chemotherapy following hypersensitivity reactions (HSR). OBJECTIVE: To provide insight into the potential utility of non-desensitization reintroduction, particularly at institutions where allergy consultation may not be available. METHODS: For 70 patients with platinum HSR who underwent rechallenge with standard (≤2 hours), extended (1-bag, 1-step, 4-6 hours), or titrated (4-to-5-bag and -step, 6-7.5 hours) infusions between 1/2014 and 7/2019, demographics and clinical characteristics were reviewed and initial and breakthrough reactions (BTR) were graded using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Tolerance (no BTR) and completion (dose completed despite BTR) were compared using Fisher's exact test. RESULTS: Patients (mean [standard deviation] age 57 [13] years, initial HSR grade 2 [1]), were rechallenged with standard (n = 8), extended (n = 23), or titrated (n = 22) infusions after oxaliplatin HSR; and standard (n = 5) or titrated (n = 12) after carboplatin HSR. Tolerance and completion were higher for extended versus (vs) standard (tolerance-87%-vs-8%, p < 0.005; completion-96%-vs-38%, p < 0.005) and titrated versus standard (tolerance-76%-vs-8%, p < 0.005; completion-79%-vs-38%, p < 0.05) infusions. CONCLUSIONS: Extended and titrated infusions may increase reintroduction safety compared to standard infusions. Further investigation into extended infusions may provide a safe alternative to standard infusions in patients who may not have access to desensitization at their institution.

Carboplatin desensitization - simplified 4-step 2-bag method.

INTRODUCTION: Our cancer program adopted a method for carboplatin desensitization (4-step 2-bag method) that administers the same intensity of drug exposure with a simplified approach to product management in comparison to a published protocol (4-step 4-bag method). METHODS: The intensity of carboplatin administration for 1:1,000, 1:100, 1:10, and 1:1 dilutions and concomitant fluid administration were compared for the 4-step 2-bag (bags A, B) and 4-step 4-bag (bags 1, 2, 3, 4) methods. Pharmacy preparation of bags A and B is described. A succinct overview of the desensitization procedure is provided. Important considerations germane to pharmacy practice are presented. Chart review of patients who underwent carboplatin desensitization with the 4-step 2-bag method between 7/13/2021 and 11/22/2023 was performed to demonstrate institutional use. RESULTS: The 4-step 2-bag method delivers similar rates of drug intensity from start of desensitization to completion of the planned dose as the previously published 4-step 4-bag method. Accuracy of regimen-based dose administration is assured by infusion of bag B contents irrespective of infusion interruptions or rate changes necessitated by patient tolerance. Bag A provides the 1:1000 dilution in a pharmaceutically elegant manner using administration rates and volumes compatible with clinical practice. CONCLUSION: The 4-step 2-bag method for carboplatin desensitization administers controlled drug titration corresponding to 1:1000, 1:100, 1:10, and 1:1 dilutions for dose administration using two compounded admixture bags. Inaugural clinical use of the 4-step 2-bag method for carboplatin desensitization at our healthcare facility has proceeded with expected patient tolerance.

Extraction Optimization and Qualitative/Quantitative Determination of Bioactive Abietane-Type Diterpenes from Three Salvia Species (Common Sage, Greek Sage and Rosemary) by 1H-qNMR.

The objective of this study was the optimization of the extraction process and the qualitative and quantitative determination of the bioactive metabolites: 12-O-methylcarnosic acid (12MCA), carnosic acid (CA), carnosol (CS), 7-O-methyl-epi-rosmanol (7MER) and rosmanol (RO) in infusions, decoctions, turbulent flow extracts, tinctures and oleolites from three Salvia species: Salvia officinalis L. (common sage, SO), Salvia fruticosa Mill. (Greek sage, SF) and Salvia rosmarinus Spenn (syn Rosmarinus officinalis L.) (rosemary, SR), using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (1H-qNMR). Regarding the aqueous extracts, decoctions appeared to be richer sources of the studied metabolites than infusions among the three plants. For SR, the turbulent flow extraction under heating was the most efficient one. The optimum time for the preparation of decoctions was found to be 5 min for SF and SO and 15 min for SR. It is noteworthy that SR tinctures were not stable in time due to decomposition of the abietane-type diterpenes CA and CS because of the polar solvent used for their preparation. Contrary to this finding, the oleolites of SR appeared to be very stable. Olive oil as a solvent for extraction was very protective for the contained abietane-type diterpenes. A preliminary stability study on the effect of the storage time of the SF on the abietane-type diterpenes content showed that the total quantity of abietanes decreased by 16.51% and 40.79% after 12 and 36 months, respectively. The results of this investigation also demonstrated that 1H-qNMR is very useful for the analysis of sensitive metabolites, like abietane-type diterpenes, that can be influenced by solvents used in chromatographic analysis.

Artificial Intelligence Sensing: Effective Flavor Blueprinting of Tea Infusions for a Quality Control Perspective.

Tea infusions are the most consumed beverages in the world after water; their pleasant yet peculiar flavor profile drives consumer choice and acceptance and becomes a fundamental benchmark for the industry. Any qualification method capable of objectifying the product's sensory features effectively supports industrial quality control laboratories in guaranteeing high sample throughputs even without human panel intervention. The current study presents an integrated analytical strategy acting as an Artificial Intelligence decision tool for black tea infusion aroma and taste blueprinting. Key markers validated by sensomics are accurately quantified in a wide dynamic range of concentrations. Thirteen key aromas are quantitatively assessed by standard addition with in-solution solid-phase microextraction sampling followed by GC-MS. On the other hand, nineteen key taste and quality markers are quantified by external standard calibration and LC-UV/DAD. The large dynamic range of concentration for sensory markers is reflected in the selection of seven high-quality teas from different geographical areas (Ceylon, Darjeeling Testa Valley and Castleton, Assam, Yunnan, Azores, and Kenya). The strategy as a sensomics-based expert system predicts teas' sensory features and acts as an AI smelling and taste machine suitable for quality controls.

Examining the effect of training with a teaching for understanding framework on intravenous therapy administration's knowledge, performance, and satisfaction of nursing students: a non-randomized controlled study.

BACKGROUND: Nursing students require improvement in their intravenous infusion therapy management skills, yet traditional training models possess deficiencies. The Teaching for Understanding (TfU) Framework can enhance the teaching-learning process and support quality education. Therefore, utilizing TfU framework for training may promote the performance of nurses. METHODS: Utilizing a non-synchronized design, 102 nurses were recruited using a convenience sampling method. Fifty-one student nurses from August 2019 to January 2021 were designated as the control group, and 51 student nurses from February 2021 to July 2022 were included as the intervention group. The control group received traditional teaching methods, while the intervention group was trained based on TfU framework. The impact was gauged through medical education environment perception, theory and practice assessments, and learning satisfaction surveys. RESULTS: After the training, there was no significant difference between the control group and the intervention group in the theory assessment. However, the practice assessment scores of the intervention group were significantly higher than those of the control group. Compared with the control group, the learning satisfaction scores of the trained nurses in the intervention group were significantly higher, exhibiting significant differences, particularly in communication ability, teamwork cooperation, summing up capability, and interest in learning improvement. Furthermore, the scores of the learning perceptions, atmosphere, social self-perceptions, and total scores of the intervention group were significantly higher. CONCLUSION: Training using TfU framework can heighten students' understanding and command over knowledge and skills, fuel their learning fervor, and enhance their communication and collaboration abilities. TfU framework should be disseminated in medical education to improve the quality of education.

Development of a model to predict vancomycin serum concentration during continuous infusion of vancomycin in critically ill pediatric patients.

Vancomycin is a frequently used antibiotic in intensive care units, and the patient's renal clearance affects the pharmacokinetic characteristics of vancomycin. Several advantages have been reported for vancomycin continuous intravenous infusion, but studies on continuous dosing regimens based on patients' renal clearance are insufficient. The aim of this study was to develop a vancomycin serum concentration prediction model by factoring in a patient's renal clearance. Children admitted to our institution between July 1, 2021, and July 31, 2022 with records of continuous infusion of vancomycin were included in the study. Sex, age, height, weight, vancomycin dose by weight, interval from the start of vancomycin administration to the time of therapeutic drug monitoring sampling, and vancomycin serum concentrations were analyzed with the linear regression analysis of the mixed effect model. Univariable regression analysis was performed using the vancomycin serum concentration as a dependent variable. It showed that vancomycin dose (p < 0.001) and serum creatinine (p = 0.007) were factors that had the most impact on vancomycin serum concentration. Vancomycin serum concentration was affected by vancomycin dose (p < 0.001) and serum creatinine (p = 0.001) with statistical significance, and a multivariable regression model was obtained as follows: Vancomycin serum concentration (mg/l) = -1.296 + 0.281 × vancomycin dose (mg/kg) + 20.458 × serum creatinine (mg/dl) (adjusted coefficient of determination, R2 = 0.66). This prediction model is expected to contribute to establishing an optimal continuous infusion regimen for vancomycin.

Subcutaneous infusion of high-dose benzathine penicillin G is safe, tolerable, and suitable for less-frequent dosing for rheumatic heart disease secondary prophylaxis: a phase 1 open-label population pharmacokinetic study.

Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal. It has previously been demonstrated that BPG delivered subcutaneously at a standard dose is safe and tolerable and has favorable pharmacokinetics, setting the scene for improved regimens with less frequent administration. The safety, tolerability, and pharmacokinetics of subcutaneous infusions of high-dose BPG were assessed in 24 healthy adult volunteers assigned to receive either 3.6, 7.2, or 10.8 MU (three, six, and nine times the standard dose, respectively) as a single subcutaneous infusion. The delivery of the BPG to the subcutaneous tissue was confirmed with ultrasonography. Safety assessments, pain scores, and penicillin concentrations were measured for 16 weeks post-dose. Subcutaneous infusion of penicillin (SCIP) was generally well tolerated with all participants experiencing transient, mild infusion-site reactions. Prolonged elevated penicillin concentrations were described using a combined zero-order (44 days) and first-order (t1/2 = 12 days) absorption pharmacokinetic model. In simulations, time above the conventionally accepted target concentration of 20 ng/mL (0.02 µg/mL) was 57 days for 10.8 MU delivered by subcutaneous infusion every 13 weeks compared with 9 days of every 4-weekly dosing interval for the standard 1.2 MU intramuscular dose (i.e., 63% and 32% of the dosing interval, respectively). High-dose SCIP (BPG) is safe, has acceptable tolerability, and may be suitable for up to 3 monthly dosing intervals for secondary prophylaxis of RHD.

Consumption of herbal infusions/decoctions and tea in Greece: a Planeterranean perspective on the results of Hydria survey.

BACKGROUND: The consumption of various herbal infusions was and is common in the traditional Mediterranean diet, and apparently are used in many other regions of the world outside of the Mediterranean region. The present study aimed to investigate the consumption of herbal infusions/decoctions and tea in a nationally representative sample of Greece, considering also their Planetary use. METHODS: 3951 adult participants of the HYDRIA Survey (2013-2014) were included from the 13 regions of Greece. The diet of participants was assessed by two 24-h dietary recalls (24-HDR) and the Food Propensity Questionnaire (FPQ). All food items were analyzed through the HYDRIA Food Composition Tables. Information on socio-demographics, lifestyle, and health characteristics during the baseline was also provided. RESULTS: 26.9% of herbal infusions and decoctions consumers are ≥ 75 years old, pensioners with a low level of education, and residents of urban areas. However, 22.2% of tea consumers belong to the 18-34-year age group, being employed with an intermediate level of education and living in an urban area. Elderly men and women use more herbal infusions/decoctions (55.4%; 40.6%) compared to tea (41.8%; 25.2%). According to FPQ, 7.1% of men and 9.7% of women use herbal infusions and decoctions four times or more per week, while 7.1 and 10.9% of men and women, respectively, consume tea at the same frequency. Green tea, mountain tea (Sideritis spp.), and black tea are reported most frequently. In addition, mountain tea (61.2%), black tea (60.3%), mixed herbal infusions/decoctions (58.4%), and sage (59.4%) are consumed mostly at breakfast, while chamomile was reported mainly at dinner or during the night (42.4%). CONCLUSIONS: Based on the FPQ results, the moderate and high consumption of herbal infusions/decoctions and tea is low in Greece, especially among adults (18-64 years). Thus, our results indicate the existence of a generation gap to the attachment to the traditional Med Diet and the consumption of herbal infusions. The present study could encourage future research to focus on herbal infusions and decoctions consumption by other populations for cross-cultural comparison, as well as on emphasizing the value of consuming locally available herbs in a Planeterranean perspective.

Design of an algorithm for the detection of intravenous fluid contamination in clinical laboratory samples.

OBJECTIVES: Contamination of blood samples from patients receiving intravenous fluids is a common error with potential risk to the patient. Algorithms based on the presence of aberrant results have been described but have the limitation that not all infusion fluids have the same composition. Our objective is to develop an algorithm based on the detection of the dilution observed on the analytes not usually included in infusion fluids. METHODS: A group of 89 cases was selected from samples flagged as contaminated. Contamination was confirmed by reviewing the clinical history and comparing the results with previous and subsequent samples. A control group with similar characteristics was selected. Eleven common biochemical parameters not usually included in infusion fluids and with low intraindividual variability were selected. The dilution in relation to the immediate previous results was calculated for each analyte and a global indicator, defined as the percentage of analytes with significant dilution, was calculated. ROC curves were used to define the cut-off points. RESULTS: A cut-off point of 20 % of dilutional effect requiring also a 60 % dilutional ratio achieved a high specificity (95 % CI 91-98 %) with an adequate sensitivity (64 % CI 54-74 %). The Area Under Curve obtained was 0.867 (95 % CI 0.819-0.915). CONCLUSIONS: Our algorithm based on the global dilutional effect presents a similar sensitivity but greater specificity than the systems based on alarming results. The implementation of this algorithm in the laboratory information systems may facilitate the automated detection of contaminated samples.

Acute Management of Hypertriglyceridemia With a Disease-Specific Intravenous Insulin Infusion Order Set.

BACKGROUND: Hypertriglyceridemia-associated acute pancreatitis is a disease lacking a standardized management approach. OBJECTIVE: The main objective of this study was to evaluate the safety and efficacy of a continuous intravenous insulin infusion order set specifically designed for managing hypertriglyceridemia. METHODS: This study compared the safety and efficacy of a standardized (postintervention) approach to managing hypertriglyceridemia to a nonstandardized (preintervention) approach. The primary efficacy outcome was the percentage of patients who achieved a triglyceride level less than 500 mg/dL. Additional outcomes included the time to achieving a triglyceride level less than 500 mg/dL and the percent reduction in triglyceride levels. The primary safety outcome was the number of patients who experienced hypoglycemia (glucose less than 70 mg/dL). RESULTS: Twenty patients were included in both the preintervention and postintervention groups. There was a significantly greater reduction in triglyceride levels observed in the postintervention group. The number of patients who achieved a triglyceride level less than 500 mg/dL in the preintervention and postintervention groups were 10 (50%) and 17 (85%), respectively, P = 0.018. Within the postintervention group, the time to achieving a triglyceride level less than 500 mg/dL in those with and without diabetes was 56.8 hours (38.2-64.0) versus 27.6 hours (19.7-45.0), respectively, P = 0.028. CONCLUSION AND RELEVANCE: Our findings demonstrate that insulin infusions are safe and effective when therapy is standardized and accounts for nursing to patient ratios. Our results provide the medical community with a standardized approach to acutely managing hypertriglyceridemia.

More time in a community setting: A service evaluation of the impact of intrathecal drug delivery systems on place of care of patients with cancer pain.

BACKGROUND: Intrathecal Drug Delivery Systems are underutilised in the management of refractory cancer pain despite evidence of their efficacy. Not all patients who are offered this treatment modality accept it. There is no current evidence that indicates if the use of intrathecal drug delivery systems impacts on place of care for patients with cancer related pain. AIMS: This service evaluation compared place of care, place of death and morphine equivalent daily dose at end of life for patients in whom Intrathecal Drug Delivery was successfully established versus those who chose comprehensive medical management. SETTING/PARTICIPANTS: A retrospective longitudinal cohort study of 45 patients with cancer pain comparing those who had ongoing analgesia successfully delivered via an implanted Intrathecal Drug Delivery System (n = 28) with those who continued to receive comprehensive medical management (n = 17). RESULTS: There was a markedly greater time spent in the community in the intrathecal group than the medical management group (median 126.5vs 25.5 days; p = 0.002) and a lower morphine equivalent daily dose at end of life (median 127.5vs 440.0 p = 0.022). CONCLUSION: In patients with advanced cancer, the successful establishment of intrathecal analgesia is associated with more time in the community and a lower morphine equivalent daily dose at end of life. The study has low numbers, and the sample was retrospectively selected. Nevertheless, these findings suggest the initial investment of time in an inpatient setting may be beneficial. Further research is required, using larger, prospective studies of patient outcomes in this setting.

Evaluation of nurses' knowledge and performance regarding preparation and injection of intravenous drugs in pediatric wards in Iran.

BACKGROUND: A error in intravenous injection in pediatric wards can cause irreparable injuries. This study aimed to determine the level of knowledge and performance of nurses in terms of preparation and injection of intravenous drugs in pediatric wards of hospitals affiliated to Isfahan University of Medical Sciences. METHODS: This cross-sectional study was conducted in 2022 on 156 nurses working in pediatric wards. The data was collected with demographic information questionnaire and the knowledge and performance of the participants were determined using a researcher-made questionnaire, including the five rights of medication administration (preparation and injection, medication error, drug side effects, family empowerment, and documentation) using self-reporting and observation methods. Formal and content validity was calculated using the opinions of 10 experts and Cronbach's alpha with 40 samples. RESULTS: The mean and standard deviation of total nurses' knowledge and performance scores were 58.31 + 10.1 and 66.1 + 14.4, respectively. Moreover, the mean and standard deviation of nurses' knowledge scores were 63.55 + 14.3 for documentation, 46.1 + 7.9 for preparation and injection, 73.9 + 12.3 for drug side effects, 58.4 + 10.2 for medication error, and 69.4 + 9.4 for family empowerment. Besides, the mean performance was 69.1 + 17.6 for documentation, 61.3 ± 9.9 for preparation and injection, 78.21 + 12 for drug side effects, 58.6 + 15 for medication error, and 65.4 + 17.7 for family empowerment. CONCLUSION: The results showed that the mean knowledge and pharmacological performance of nurses working in pediatric wards in different areas of the principles of medicine were not at the desired level, and this can affect children adversely.

Examining safety and efficacy of a fixed concentration heparin dosing strategy for anticoagulation in neonatal extracorporeal membrane oxygenation.

OBJECTIVES: The paediatric intensive care unit changed heparin infusion dosing from a variable weight-based concentration to a fixed concentration strategy, when smart pump-based drug library was introduced. This change meant significantly lower rates of infusion were needed for the same dose of heparin in the neonatal population. We performed a safety and efficacy assessment of this change. METHODS: We performed a retrospective single-centre evaluation based on data from respiratory VA-extracorporeal membrane oxygenation (ECMO) patients weighing ≤5 kg, pre and post the change to fixed strength heparin infusion. Efficacy was analysed by distribution of activated clotting times (ACT) and heparin dose requirements between the groups. Safety was analysed using thrombotic and haemorrhagic event rates. Continuous variables were reported as median, interquartile ranges, and non-parametric tests were used. Generalised estimating equations (GEE) were used to analyse associations of heparin dosing strategy with ACT and heparin dose requirements in the first 24 h of ECMO. Incidence rate ratios of circuit related thrombotic and haemorrhagic events between groups were analysed using Poisson regression with offset for run hours. RESULTS: 33 infants (20 variable weight-based, 13 fixed concentration) were analysed. Distribution of ACT ranges and heparin dose requirements were similar between the two groups during the ECMO run and this was confirmed by GEE. Incidence rate ratios of thrombotic (fixed v weight-based) (1.9 [0.5-8], p = .37), and haemorrhagic events (0.9 [0.1-4.9], p = .95) did not show statistically significant differences. CONCLUSIONS: Fixed concentration dosing of heparin was at least equally effective and safe compared to a weight-based dosing.

Interaction of Angiotensin II AT1 Receptors with Purinergic P2X Receptors in Regulating Renal Afferent Arterioles in Angiotensin II-Dependent Hypertension.

In angiotensin II (Ang II)-dependent hypertension, Ang II activates angiotensin II type 1 receptors (AT1R) on renal vascular smooth muscle cells, leading to renal vasoconstriction with eventual glomerular and tubular injury and interstitial inflammation. While afferent arteriolar vasoconstriction is initiated by the increased intrarenal levels of Ang II activating AT1R, the progressive increases in arterial pressure stimulate the paracrine secretion of adenosine triphosphate (ATP), leading to the purinergic P2X receptor (P2XR)-mediated constriction of afferent arterioles. Thus, the afferent arteriolar tone is maintained by two powerful systems eliciting the co-existing activation of P2XR and AT1R. This raises the conundrum of how the AT1R and P2XR can both be responsible for most of the increased renal afferent vascular resistance existing in angiotensin-dependent hypertension. Its resolution implies that AT1R and P2XR share common receptor or post receptor signaling mechanisms which converge to maintain renal vasoconstriction in Ang II-dependent hypertension. In this review, we briefly discuss (1) the regulation of renal afferent arterioles in Ang II-dependent hypertension, (2) the interaction of AT1R and P2XR activation in regulating renal afferent arterioles in a setting of hypertension, (3) mechanisms regulating ATP release and effect of angiotensin II on ATP release, and (4) the possible intracellular pathways involved in AT1R and P2XR interactions. Emerging evidence supports the hypothesis that P2X1R, P2X7R, and AT1R actions converge at receptor or post-receptor signaling pathways but that P2XR exerts a dominant influence abrogating the actions of AT1R on renal afferent arterioles in Ang II-dependent hypertension. This finding raises clinical implications for the design of therapeutic interventions that will prevent the impairment of kidney function and subsequent tissue injury.

Pyrrolizidine Alkaloids in Food on the Italian Market.

Pyrrolizidine alkaloids (PAs) are secondary metabolites produced by over 6000 plant species worldwide. PAs enter the food chain through accidental co-harvesting of PA-containing weeds and through soil transfer from the living plant to surrounding acceptor plants. In animal studies, 1,2-unsaturated PAs have proven to be genotoxic carcinogens. According to the scientific opinion expressed by the 2017 EFSA, the foods with the highest levels of PA contamination were honey, tea, herbal infusions, and food supplements. Following the EFSA's recommendations, data on the presence of PAs in relevant food were monitored and collected. On 1 July 2022, the Commission Regulation (EU) 2020/2040 came into force, repealed by Commission Regulation (EU) 2023/915, setting maximum levels for the sum of pyrrolizidine alkaloids in certain food. A total of 602 food samples were collected from the Italian market between 2019 and 2022 and were classified as honey, pollen, dried tea, dried herbal infusions, dried herbs, and fresh borage leaves. The food samples were analyzed for their PA content via an in-house LC-MS/MS method that can detect PAs according to Regulation 2023/915. Overall, 42% of the analyzed samples were PA-contaminated, 14% exceeded the EU limits, and the items most frequently contaminated included dried herbs and tea. In conclusion, the number of food items containing considerable amounts of PAs may cause concern because they may contribute to human exposure, especially considering vulnerable populations-most importantly, children and pregnant women.