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.

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.

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.

Neurocognitive effects of repeated ketamine infusion treatments in patients with treatment resistant depression: a retrospective chart review.

BACKGROUND: Ketamine has emerged as a rapid-acting antidepressant in treatment-resistant depression (TRD) increasingly used in non-research, clinical settings. Few studies, however, have examined neurocognitive effects of repeated racemic ketamine infusion treatments in patients with TRD. In an effort to identify potential effects after serial infusions, we conducted a retrospective chart review to identify statistically significant changes in cognition in patient undergoing serial intravenous infusions; concomitantly, we examined baseline cognition as potential predictor of anti-depressant potential. METHODS: Twenty-two patients with TRD were examined after they finished the induction phase of 8-10 repeated intravenous ketamine infusions and completed the assessments of their depressive symptoms (measured by the 16-item Quick Inventory of Depressive Symptomatology-Self Report Scale: QIDS-SR16) and cognitive function (measured by the Montreal Cognitive Assessment: MoCA) before the first and the last ketamine treatments. RESULTS: Repeated ketamine infusions administered through an escalating dose protocol with 8-10 infusion sessions produced a 47.2% reduction response in depression; there was no evidence of impairment as reflected in MoCA testing. There was a moderate association between baseline cognition and antidepressant response with a Pearson correlation of 0.453. CONCLUSION: In this naturalistic sample of patients with TRD in our clinical service, repeated ketamine infusions significantly decreased depression symptoms without impairing cognitive performance. The baseline cognition may positively predict antidepressant responses of repeated ketamine treatment.

Rapid infusion of fish oil-based lipid emulsions: Is there a risk of fat overload syndrome? A case report of rapid administration.

WHAT IS KNOWN AND OBJECTIVES: Errors involving the delivery of IVFE containing soybean oil have known significant complications, including fat overload syndrome. However, little is known regarding the risks of fat overload syndrome with other types of lipid emulsions. CASE SUMMARY: We describe a medication administration error that resulted in rapid fish oil-base lipid emulsion (Omegaven) infusion in a five-month-old infant with parenteral nutrition associated liver disease (PNALD). The medication administration error resulted in bolus infusion of Omegaven over 12 min (5 g/kg/h) instead of 12 h (0.083 g/kg/h). WHAT IS NEW AND CONCLUSION: No adverse reactions were notes because of the rapid infusion, supporting conclusion that rapid infusion of fish oil will not result in fat overload syndrome.

The Effects of Intravenous Fluid Viscosity on the Accuracy of Intravenous Infusion Flow Regulators.

Intravenous infusion flow regulators (IIFRs) are widely used devices but it is unknown how much the difference between the IIFR scale and the actual flow rate depends on the viscosity of the intravenous (IV) fluid. This study evaluated the effects of viscosity on the flow rate of five IV fluids (0.9% normal saline, Hartmann's solution, plasma solution-A, 6% hetastarch, and 5% albumin) when using IIFRs. The viscosity of crystalloids was 1.07-1.12 mPa·s, and the viscosities of 6% hetastarch and 5% albumin were 2.59 times and 1.74 times that of normal saline, respectively. When the IIFR scales were preset to 20, 100, and 250 mL/hr, crystalloids were delivered at the preset flow rate within a difference of less than 10%, while 6% hetastarch was delivered at approximately 40% of the preset flow rates and 5% albumin was approximately 80% transmitted. When delivering colloids, IIFRs should be used with caution.

Unraveling the Mystery of Polyvalent Immunoglobulins in Belgium: Do We Have an Indication?

INTRODUCTION: Worldwide, polyvalent immunoglobulin (Ig) use is rising. Together with the limited supply, this puts pressure on Ig availability. A clear overview on a country's usage pattern helps in forecasting future needs. This research aims to provide an overview of Ig use in Belgium on the different indications, including an estimation of off-label use. METHODS: Multiple data sources were used. Existing claims data were explored for reimbursed Ig use between 2010 and 2018. General 2018 sales data from the firms were compared to the reimbursed use to serve as a proxy for off-label use. Indication-specific information was retrieved via a proxy: diagnostic codes available during day-care and inpatient hospitalization. RESULTS: In 2018, 7,556 patients had reimbursed Ig. The most prevalent indication, both in terms of patient numbers and volume, was primary immunodeficiency (PID). In Belgian hospitals, the currently reimbursed indications represented 84.4% of patients (PID [≈35%], secondary immunodeficiency [SID] [≈21%], primary immune thrombocytopenia [≈10%], chronic inflammatory demyelinating neuropathy [CIDP] [≈8%], Guillain-Barre syndrome [≈6%], Kawasaki [≈2%], streptococcal toxic shock [≈2%] and multiple motor neuropathy [≈1%]), and 82.4% of Ig use (predominantly PID [≈33%] and CIDP [≈21%]). Although no direct data on off-label use were available, crude estimates derived from indirect sources showed a proportion of around 15.4%. CONCLUSION: Our research offers the first comprehensive overview on Ig use in Belgium, including a detailed description of reimbursed use, as well as approximations to off-label use. In view of increasing pressure on Ig availability, better understanding Ig needs and trends, would benefit from an effective indication-specific national registry system (ideally covering both reimbursed and nonreimbursed use).

Infiltration and extravasation of intravenous infusions in children-value of high-quality care on outcome.

OBJECTIVE: To study the value of high-quality care on the outcome of infiltration and extravasation of peripheral intravenous infusions in children. METHODS: The retrospective cohort study was conducted at the Third Affiliated Hospital of Zunyi Medical University, Guizhou, China, and comprised secondary-data analysis on children aged <3 years hospitalized between January 2013 and September 2019. The sample was divided into control group A and high-quality care group B. Outcomes noted were severity of infiltration and extravasation of intravenous infusions graded using the Infusion Nurses Society score. Data was analysed using SAS software version 9.4. RESULTS: Of the 16,268 subjects, 2147(13%) were in control group A and 14,121(87%)were in the high-quality care group B. Group B had lower severity of infiltration and extravasation compared to group A (odds ratio: 0.75; 95% confidence interval: 0.63-0.90). The causes of infiltration and extravasation included agents with high osmolarity, poor condition of veins, guardianship negligence and allergies to dressing materials (p<0.05). CONCLUSIONS: High-quality care was more effective than routine care in reducing the incidence and degree of infiltration and extravasation of peripheral intravenous infusions.

The Optimizing Background Infusion Mode Decreases Intravenous Patient-Controlled Analgesic Volume and Opioid Consumption Compared to Fixed-Rate Background Infusion in Patients Undergoing Laparoscopic Cholecystectomy: A Prospective, Randomized, Controlled, Double-Blind Study.

Background and objectives: The fixed-rate continuous background infusion mode with bolus dosing is a common modality for intravenous patient-controlled analgesia (PCA). However, some patients suffer from inadequate analgesia or opioid-related adverse effects due to the biphasic pattern of postoperative pain. Therefore, we investigated the postoperative analgesic efficacy of PCA using an optimizing background infusion mode (OBIM) where the background injection rate varies depending on the patient's bolus demand. Materials and Methods: We prospectively enrolled 204 patients who underwent laparoscopic cholecystectomy in a randomized, controlled, double-blind study. Patients were allocated to either the optimizing (group OBIM) or the traditional background infusion group (group TBIM). The numeric rating scale (NRS) score for pain was evaluated at admission to and discharge from the recovery room, as well as at the 6th, 24th, and 48th postoperative hours. Data on bolus demand count, total infused volume, and background infusion rate were downloaded from the PCA device at 30-min intervals until the 48th postoperative hour. Results: The NRS score was not significantly different between groups throughout the postoperative period (p = 0.621), decreasing with time in both groups (p < 0.001). The bolus demand count was not significantly different between groups throughout (p = 0.756). The mean total cumulative infused PCA volume was lower in group OBIM (84.0 (95% confidence interval: 78.9-89.1) mL) than in group TBIM (102 (97.8-106.0) mL; p < 0.001). The total cumulative opioid dose in fentanyl equivalents, after converting sufentanil to fentanyl using an equipotential dose ratio, was lower in group OBIM (714.1 (647.4-780.9) µg) than in group TBIM (963.7 (870.5-1056.9) µg); p < 0.001). The background infusion rate was significantly different between groups throughout the study period (p < 0.001); it was higher in group OBIM than in group TBIM before the 12th postoperative hour and lower from the 18th to the 48th postoperative hour. Conclusions: The OBIM combined with bolus dosing reduces the cumulative PCA volume and opioid consumption compared to the TBIM combined with bolus dosing, while yielding comparable postoperative analgesia and bolus demand in patients undergoing laparoscopic cholecystectomy.

BAY 81-8973 demonstrated efficacy, safety and joint status improvement in patients with severe haemophilia A in the LEOPOLD I extension for ≤2 years.

OBJECTIVES: BAY 81-8973 (Kovaltry® ), a full-length, unmodified, recombinant human factor VIII, provided excellent bleeding control for patients with haemophilia A in the pivotal 1-year LEOPOLD I trial. The LEOPOLD I extension evaluated long-term efficacy and safety of BAY 81-8973 prophylaxis. METHODS: After completing LEOPOLD I, patients continued receiving 20-50 IU/kg BAY 81-8973 two- or three-times weekly in the extension. Outcomes included annualised bleeding rate (ABR) and haemostasis during surgery. RESULTS: Fifty-five patients aged 12-65 years participated in the extension. Median (range) exposure days during the 2-year total study period was 309 (115-355). No patient switched regimens. Median (Q1; Q3) ABR for all bleeds was 2.0 (1.0; 6.1) during the pivotal study, 2.0 (0.0; 5.2) during the extension, and 2.0 (0.5; 5.5) combined. The proportion of joint bleeds affecting target joints decreased (pivotal study: 90.9%, extension: 60.0%). Haemostasis was assessed as excellent/good in all five major surgeries. One serious adverse event (myocardial infarction) occurred in a patient with cardiovascular risk factors. No patients developed inhibitors. CONCLUSIONS: BAY 81-8973 prophylaxis efficacy outcomes in the pivotal study were maintained or, in the case of joint protection, improved during the extension, with a safety and tolerability profile consistent with previous experience.

Choice of maintenance intravenous fluids among paediatric residents in Canada.

BACKGROUND: Recent literature and guidelines support routine use of isotonic intravenous (IV) fluids for maintenance therapy in hospitalized infants and children. Current prescribing practices are unknown. OBJECTIVE: To elicit paediatric residents' choice of maintenance IV fluids, particularly with regard to tonicity, in a variety of clinical scenarios and patient ages. We hypothesized that residents would choose isotonic fluids in most cases, but there would be substantially more variability in fluid choice in the neonatal age group. METHODS: An Internet-based survey was e-mailed to trainees in the 17 paediatric residency programs across Canada, via the Canadian Paediatric Program Directors. The survey instrument included questions related to training, followed by a series of questions eliciting choice of IV fluid in a variety of clinical situations. RESULTS: A total of 147 survey responses were submitted (22% response rate). Isotonic solutions were selected by >75% across all clinical scenarios involving infants and children. Very hypotonic fluids were seldom chosen. There was more variability in fluid choice in neonates, with evidence of significant differences in fluid tonicity based on senior versus junior resident status and geographical location. CONCLUSIONS: Results imply a predominance of isotonic fluid use in infants and children, suggesting that clinical practice has changed in response to risk of hyponatremia with hypotonic IV fluids. As hypothesized, there was more variability with respect to choice of maintenance fluids in neonates. This likely reflects a paucity of guidance in an age group with unique physiologic factors affecting fluid and electrolyte status.

BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results.

INTRODUCTION: BAY 94-9027 is an extended-half-life, site-specifically PEGylated, B-domain-deleted recombinant factor VIII (FVIII). The PROTECT VIII main study demonstrated efficacy of bleed control using extended-interval prophylaxis with BAY 94-9027 for 36 weeks. AIM: To report long-term efficacy and safety of prophylaxis with BAY 94-9027 in a descriptive analysis of the ongoing PROTECT VIII extension with a total treatment time of up to >5 years. METHODS: Previously treated males aged 12-65 years with severe haemophilia A who completed the PROTECT VIII main study were eligible for the open-label extension. Patients received on-demand treatment or prophylaxis (30-40 IU/kg twice weekly, 45-60 IU/kg every 5 days, or 60 IU/kg every 7 days) and could switch regimens as needed. RESULTS: Patients (N = 121; on demand, n = 14; prophylaxis, n = 107) accumulated a median (range) of 3.9 years (297-1965 days) and 223 (23-563) total exposure days by 31 January 2018. During the extension, median (quartile [Q]1; Q3) annualized bleeding rates (ABRs) for total bleeds were 1.6 (0.3; 4.6) for patients receiving prophylaxis and 34.1 (20.3; 36.6) for patients receiving on-demand treatment. ABRs for twice-weekly (n = 23), every-5-days (n = 33), every-7-days (n = 23) and variable frequency (n = 28) treatments were 1.7, 1.2, 0.7 and 3.1, respectively. Of prophylaxis patients, 20.6% were bleed-free throughout the extension (median time, 3.2 years), and 44.5% were bleed-free during the last 6 months. No patients developed FVIII inhibitors. CONCLUSIONS: BAY 94-9027 prophylaxis was efficacious and well tolerated with dosing intervals up to every 7 days for a median (range) of 3.9 years (0.8-5.4 years).

A French observational study describing the use of human polyvalent immunoglobulins in hematological malignancy-associated secondary immunodeficiency.

OBJECTIVE: To describe the characteristics of patients suffering from secondary immunodeficiencies (SID) associated with hematological malignancies (HM), who started immunoglobulin replacement therapy (IgRT), physicians' expectations regarding IgRT, and IgRT modalities. METHODS: Non-interventional, prospective French cross-sectional study. RESULTS: The analysis included 231 patients (66 ± 12 years old) suffering from multiple myeloma (MM) (N = 64), chronic lymphoid leukemia (CLL) (N = 84), aggressive non-Hodgkin B-cell lymphoma (aNHL) (N = 32), indolent NHL (N = 39), acute leukemia (N = 6), and Hodgkin disease (N = 6). Of the HM, 47% were currently treated, 42% were relapsing or refractory, 23% of patients had received an autologous hematopoietic stem-cell transplant, and 1% had received an allograft. Serum immunoglobulin trough levels in 195 individuals were less than 5 g/L in 68.7% of cases. Most patients had a history of recurrent infections. Immunoglobulin dose was about 400 mg/kg/mo. Half of patients started with subcutaneous infusion. When starting IgRT, physicians mainly expected to prevent severe and moderate infections. They also anticipated improvement in quality of life and survival which is beyond evidence-based medicine. CONCLUSION: NHL is a frequent condition motivating IgRT besides well-recognized indications. Physicians mainly based the decision of starting IgRT on hypogammaglobulinemia and recurrence of infections but, irrespective of current recommendations, were also prepared to start IgRT prophylactically even in the absence of a history of infections.

Procedural and documentation variations in intravenous infusion administration: a mixed methods study of policy and practice across 16 hospital trusts in England.

BACKGROUND: Procedural and documentation deviations relating to intravenous (IV) infusion administration can have important safety consequences. However, research on such deviations is limited. To address this we investigated the prevalence of procedural and documentation deviations in IV infusion administration and explored variability in policy and practice across different hospital trusts. METHODS: We conducted a mixed methods study. This involved observations of deviations from local policy including quantitative and qualitative data, and focus groups with clinical staff to explore the causes and contexts of deviations. The observations were conducted across five clinical areas (general medicine, general surgery, critical care, paediatrics and oncology day care) in 16 National Health Service (NHS) trusts in England. All infusions being administered at the time of data collection were included. Deviation rates for procedural and documentation requirements were compared between trusts. Local data collectors and other relevant stakeholders attended focus groups at each trust. Policy details and reasons for deviations were discussed. RESULTS: At least one procedural or documentation deviation was observed in 961 of 2008 IV infusions (deviation rate 47.9%; 95% confidence interval 45.5-49.8%). Deviation rates at individual trusts ranged from 9.9 to 100% of infusions, with considerable variation in the prevalence of different types of deviation. Focus groups revealed lack of policy awareness, ambiguous policies, safety and practicality concerns, different organisational priorities, and wide variation in policies and practice relating to prescribing and administration of IV flushes and double-checking. CONCLUSIONS: Deviation rates and procedural and documentation requirements varied considerably between hospital trusts. Our findings reveal areas where local policy and practice do not align. Some policies may be impractical and lack utility. We suggest clearer evidence-based standardisation and local procedures that are contextually practical to address these issues.

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose.

BACKGROUND: Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. METHODS: A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion. RESULTS: Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml-1 (-6.7 to -2.3) for the first infusion, +0.2 mg ml-1 (-0.9 to +0.4) for the second infusion and -0.3 mg ml-1 (-0.6 to +0.2) for third and fourth infusions. CONCLUSION: There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors.

Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression.

AIM: Treatment-resistant depression patients are more likely to suffer from comorbid physical and mental disorders, experience marked and protracted functional impairment, and incur higher health-care costs than non-affected individuals. Magnesium sulfate is a treatment option that may offer great potential for patients with treatment-resistant depression based on prior work in animals and humans. METHODS: Twelve subjects with mild or moderate treatment-resistant depression were randomized into a double-blind crossover trial to receive an infusion of 4 g of magnesium sulfate in 5% dextrose or placebo infusion of 5% dextrose with a 5-day washout in between the 8-day intervention period. Subjects were assessed before and after the intervention for serum and urine magnesium, lipid panel, the Hamilton Rating Scale for Depression, and the Patient Health Questionnaire-9. RESULTS: We found a difference in serum magnesium from day 2 to 8 (pre-infusion) (P < 0.002) and from baseline to day 8 (P < 0.02). No changes were noted on the Hamilton Rating Scale for Depression or the Patient Health Questionnaire-9 24 h post-treatment, but as serum magnesium increased from baseline to day 7, the Patient Health Questionnaire-9 decreased from baseline to day 7 (P = 0.02). CONCLUSION: Magnesium sulfate did not significantly affect depression 24 h post-infusion, but other results were consistent with the literature. The association between changes in serum magnesium and the Patient Health Questionnaire-9 supports the idea that magnesium sulfate may be used to address treatment-resistant depression, an ongoing medical challenge.

Delays during the administration of acetylcysteine for the treatment of paracetamol overdose.

BACKGROUND: The licensed intravenous acetylcysteine regimen for treating paracetamol overdose in most countries uses three separate infusions over 21 h. This complex regimen, requiring different infusion concentrations and rates, has been associated with administration errors. The aim of the present study was to assess the extent of administration delays occurring during this acetylcysteine regimen. METHOD: A 6-month retrospective observational study was conducted at three English teaching hospitals with clinical toxicology services from October 2014. Patients aged 16 years and over, treated with intravenous acetylcysteine for paracetamol overdose, were included. The start times for infusions were recorded and the delays compared with the prescribed infusion times were calculated. Anaphylactoid reactions, intravenous cannula problems, overdose intent and smoking status were recorded to assess their contribution to delays. RESULTS: From 263 cases identified, 198 met the study inclusion criteria. The median time between the start of infusions 1 and 3 was delayed from the intended 5 h by a median (interquartile range) of 90 (50-163) min, with 135 (68%) cases delayed by more than 1 h. Significantly longer delays were observed in patients with anaphylactoid reactions [median delay 267 (217-413) min, n = 8] and accidental/supratherapeutic overdose [median delay 170 (95-260) min, n = 29]. There were no significant differences between smokers and nonsmokers, or for patients with intravenous cannula problems. CONCLUSION: Long delays were identified during the three-infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge.

Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain.

OBJECTIVE: Use of low-dose ketamine infusions in the emergency department (ED) has not previously been described, despite routine use in perioperative and other settings. Our hypothesis was that a low-dose ketamine bolus followed by continuous infusion would 1) provide clinically significant and sustained pain relief; 2) be well tolerated; and 3) be feasible in the ED. METHODS: We prospectively administered 15 mg intravenous ketamine followed immediately by continuous ketamine infusion at 20 mg/h for 1 hour. Optional morphine (4 mg) was offered at 20, 40, and 60 minutes. Pain intensity, vitals signs, level of sedation, and adverse reactions were assessed for 120 minutes. RESULTS: A total of 38 patients were included with a median initial numerical rating scale (NRS) pain score of 9. At 10 minutes, the median reduction in pain score was 4, with 7 patients reporting a score of 0. At 60 and 120 minutes, 25 and 26 patients, respectively, reported clinically significant pain reduction (decrease NRS score > 3). Heart rate, blood pressure, respiratory rate, and oxygen saturation remained stable. Mild or moderate side effects including dizziness, fatigue, and headache were common. Patient satisfaction was high; 85% reported they would have this medication again for similar pain. CONCLUSION: A low-dose ketamine infusion protocol provided significant pain relief with mostly mild side effects and no severe adverse events.

Oral cyclosporine A treatment is feasible after myeloablative conditioning in allogeneic hematopoietic stem cell transplantation.

WHAT IS KNOWN AND OBJECTIVE: The target level and route of administration of cyclosporine A (CsA) differ between transplantation centres. It is unclear whether oral CsA is sufficient to maintain target level of CsA. CASE SUMMARY: We retrospectively analysed data from 48 adult patients, who underwent myeloablative hematopoietic stem cell transplantation. Twenty-one patients (44%) tolerated CsA orally throughout the transplantation period without increased incidence of acute graft versus host disease(aGVHD). Low concentration of CsA in week 2 was associated with increased incidence of aGVHD. WHAT IS NEW AND CONCLUSION: Oral administration of CsA is safe, less time-consuming and economically advantageous. Close monitoring of CsA concentration is important.

The impact of a computerized physician order entry system on medical errors with antineoplastic drugs 5 years after its implementation.

WHAT IS KNOWN AND OBJECTIVE: Computerized physician order entry (CPOE) systems reduce medical errors (MEs). Nevertheless, a CPOE system may also lead to new types of errors, especially when it is first implemented. The objectives of this study were to determine the impact of a CPOE on the number of MEs and to identify the types of MEs in prescriptions issued by the Haematology Department 5 years after the implementation of the CPOE system. METHODS: We conducted a prospective analytical study on the implementation of a CPOE system at the Pharmacy Department of the Hospital Ramon y Cajal (Madrid, Spain). The study comprised three phases: a pre-implementation phase, an implementation phase conducted in the Haematology Department and a post-implementation phase, which was conducted 5 years after the implementation of the CPOE system. One hundred and fifty prescriptions per pre- and post-implementation phase were consecutively included in the study. A previously described classification scheme was used to detect and classify MEs. RESULTS AND DISCUSSION: The implementation of a CPOE system was associated with a large reduction in MEs. One hundred and fourteen patients (pre-implementation phase) were compared to 82 patients (post-implementation phase). The total number of MEs per 100 patients decreased from 236·8 (95% CI: 212·1-261·3) to 10·9 (95% CI: 5·8-19·6), with an absolute risk reduction of 36·2 (95% CI: 32·6-39·9). The percentage of prescriptions with an ME decreased from 37·5% to 1·2% (P < 0.001). In the pre-implementation phase, the drugs most frequently associated with MEs were rituximab (35·9%), cyclophosphamide (13%) and methotrexate (7%). In the post-implementation phase, 44·4% of prescription errors involved methotrexate. Five years after the implementation of the CPOE system, the majority of MEs were eliminated, the number of remaining errors (quantity, concentration and ambiguous prescription errors) decreased, and no new types of ME were detected. WHAT IS NEW AND CONCLUSION: The CPOE system almost completely eliminated MEs with antineoplastic drugs in the Haematology Department. No new types of MEs were observed once physicians had become accustomed to using the system. However, some MEs were not eliminated. Constant diligence is needed to analyse and evaluate MEs associated with the CPOE system and their causes, such that the limitations of CPOE can be identified and overcome and the medication-use process associated with antineoplastic agents improved.