Dose Omission Research Articles

Paediatric Emergency Nurses' Perception of Medication Errors: A Qualitative Study.

To explore paediatric emergency nurses' perceptions of medication administration errors. A qualitative, ethnomethodological, descriptive study. The participants were nurses working in the paediatric emergency department. Data were collected through in-depth individual interviews with paediatric emergency nurses. The study excluded nurses employed for less than six months. Ten individual interviews were carried out. All interviews were face-to-face and audio-recorded with the participant's consent. Interviews took between 52 min and 1 h 25 min. A questions guide was followed during the interviews. The analysis of the data was carried out according to the scheme proposed by Taylor and Bogdan. The participants' discourse revealed three main categories: Safety culture, transmitted by supervisors and safety groups. Teamwork, with good communication and a positive relationship. Error management, the lack of formal support and negative feelings despite an understanding of the multifactorial nature of errors. The study identifies several challenges in the healthcare system. Emphasis was placed on the perception of errors in terms of patient harm, while near misses or dose delays or omissions are not treated as errors. Although institutions have implemented safety culture strategies, nurses have not fully embraced them. There is a need to promote a positive safety culture and a safe working environment that encourages communication within the team. The hospital should provide training in safe management and patient safety and develop effective protocols. This study was not registered.

Comparative evaluation of adverse drug reactions for tenofovir alafenamide and tenofovir disoproxil fumarate using the FAERS Database: a disproportionality analysis.

Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are widely used nucleoside reverse transcriptase inhibitors (NRTIs), necessitating a thorough understanding of their safety profiles to ensure optimal patient care and treatment adherence. We employed statistical methods including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) to compare and evaluate the safety profiles of these NRTIs. TAF was significantly associated with weight increase (ROR: 6.43; 95% CI: 5.93-6.96) and specific psychiatric disorders. TDF showed a notable signal for renal disorders and product-related issues, including product dose omission (ROR: 3.53; 95% CI: 3.22-3.87). Additionally, the study highlighted differences in safety signals related to pregnancy outcomes, with TAF having a higher ROR for maternal exposure (ROR: 7.83; 95% CI: 7.06-8.69) and TDF for fetal exposure (ROR: 4.51; 95% CI: 3.93-5.18), underscoring the need for cautious use in pregnant women. The comparative analysis also identified signals for osteonecrosis (ROR: 108.81; 95% CI: 106.25-111.43) and bone loss (ROR: 714; 95% CI: 685.49-743.68) for TAF and TDF, respectively, highlighting the importance of bone health considerations in treatment plans. These findings underscore the importance of personalized antiviral therapy and patient safety.

Reduction in preventable time-critical dose omissions: impact of electronic medication management systems on in-patients

Background: The omission of time-critical medication doses may result in poor patient outcomes. There are few publications about the influence of electronic medication management (EMM) systems, including automated dispensing cabinets (ADC), on timely medication administration. The study aimed to evaluate the influence of EMM systems, including ADCs, on timely medication administration 6 and 30 months after EMM implementation, focussing on preventable time-critical medication dose omissions and documented reasons for not administering a dose. Methods: Data on doses of regular inpatient medications not administered were obtained from electronic medication records (EMR) over 1 week in March 2019 and 4 weeks in March 2021. An omission was a dose not administered before the next due dose. Time-critical medications were defined using the health service’s guidelines. Reasons for doses not being administered were obtained from nursing documentation in the EMR collated from digital health reports. Reasons for time-critical medication doses not given were defined as ‘valid’ or ‘preventable’. Results: In 2019 and 2021, 620 and 2524 patients with 44,756 and 146,940 scheduled medication doses were reviewed. Of these, 4385 (9.8%) and 19,610 (13.4%) doses were not administered. In 2019 and 2021, there were 593 (1.3%) and 1811 (1.2%), p < 0.0001, time-critical doses not administered. Preventable time-critical dose omissions decreased from 0.20% in 2019 to 0.15% (p = 0.015) in 2021. Wards with ADCs had a significantly lower rate of time-critical dose omissions compared to those without ADCs (1.1% vs 1.3%, p = 0.014). Conclusion: With the introduction of an EMM system, there was a decrease in the rate of time-critical medications not administered, including a reduced rate of preventable omissions over the 24-month period. Regular assessment of time-critical medication administration will help target patient safety improvements.

Using the Failure Mode and Effect Analysis Tool to Improve the Automatic Stop Order Process.

Automatic stop orders (ASOs) in computerized prescription order entry (CPOE) systems predefine the length of treatment. This can improve resource use for select therapies (e.g., empirical antibiotics). However, root cause analysis of dose omission errors identified inappropriate ASO-directed termination of medications without prescriber notification. This quality improvement initiative aimed to identify potential failures of the medication ASO processes to develop a new workflow and anticipate issues that may arise after implementation. A failure mode and effect analysis (FMEA) was conducted following Institute of Healthcare Improvement guidance. A multidisciplinary ASO-FMEA team reviewed the existing workflow. Failure modes, risk priority numbers (RPNs), and interventions were identified and assessed. The RPNs calculated for the proposed new workflow (assuming all recommendations were implemented) were compared with those of the existing workflow. Eight failure modes, 17 effects, and 31 causes were identified in the five workflow steps (mean RPN 365.4; median 280). Specific, measurable, achievable, realistic, and time-bound interventions were proposed. Assuming successful implementation of all recommendations, the RPNs of the proposed workflow (mean 117.6; median 112) were significantly lower (p < 0.05). When modifying existing CPOE systems, FMEA may identify possible failures that can be addressed before the implementation of a new process. This may prevent errors, improving medication safety. Regardless, continuous audit and monitoring are required to ensure the effectiveness of implemented changes.

Exploring Novel Adverse Events of Nefecon

BackgroundNefecon, the first innovative drug approved by both the US FDA and European EMA for IgA nephropathy, lacked comprehensive real-world assessments of its adverse events (AEs). MethodsWe leveraged post-marketing data of Nefecon from the US FDA Adverse Event Reporting System, employing disproportionate analysis to detect positive signals at the system organ class (SOCs) and preferred terms (PTs) levels. Duplicate AEs related to budesonide and those previously reported in studies were excluded through the use of the Medical Dictionary of Regulatory Activities. Our analysis encompassed time to onset (TTO), Weibull shape parameter (WSP) evaluation, cumulative incidence, clinical prioritization evaluation and subgroup analysis based on gender and age. ResultsA total of 1515 individuals with IgA nephropathy were included. Eight positive SOC signals and 23 positive PT signals were identified, including four PTs (asthenia, malaise, product dose omission issue, and anxiety) representing novel AEs newly identified in this study. None of the positive PTs were classified as high clinical priority, with only acne, hypertension, swelling face, and weight increased considered as moderate clinical priority events. The median time to TTO was 31 days. All WSP test results indicated an early failure type profile. Lastly, subgroup analysis provided further insights into the relative risk of specific AEs. ConclusionsNefecon demonstrates a favorable safety profile, with no high-priority clinical events identified. The identification of novel AEs and subgroup-specific high-risk events fills a gap in existing studies and offers valuable insights for early clinical vigilance.

Association between Vitamin D Deficiency and Serologic Response to Hepatitis B Virus Vaccination among Heavy Industry Workers.

Hepatitis B virus (HBV) vaccination has decreased the overall incidence of HBV infection; however, approximately 5 to 10% of people are non-responders to the vaccination. This study investigated the factors associated with non-response to HBV vaccination, with an emphasis on vitamin D deficiency (VDD). This retrospective observational study focused on adult workers in a single heavy industry. Individuals with negative initial hepatitis B surface antibody (anti-HBs) levels prior to vaccination and who then received a two- or three-dose series of HBV vaccinations were enrolled. The study endpoint was failure to achieve a seroprotective antibody response, defined as an anti-HBs titer less than 10 mIU/mL. Propensity score matching (PSM) and binary logistic regression models were used to adjust the outcomes for other clinical characteristics. Among 760 workers, 566 (74.5%) exhibited VDD. The non-response rates to HBV vaccination were 13.4% (76/566) and 5.7% (11/194) among workers with and without VDD, respectively (p = 0.005). Even after adjustment using PSM, VDD was still associated with a higher rate of response failure (adjusted odds ratio 2.74; 95% confidence interval 1.40-5.38, p = 0.003). The binary logistic regression model showed that VDD, older age, omission of the third vaccine dose, lower initial anti-HBs titer, and current smoking were associated with response failure. Our study suggests that VDD may impair the serologic response following HBV vaccination. Further research is needed to evaluate the effectiveness of vitamin D supplementation in increasing the response to HBV vaccination.

Postmarketing Reports of Incomplete Dosing-Related Complications with Self-Injected PCSK9 Inhibitors: A Descriptive Study and Disproportionality Analysis.

Evolocumab and alirocumab are self-injected proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors indicated for low-density lipoprotein cholesterol reduction. Complications in the use or functionality of self-injection devices may precipitate incomplete dosing. This study sought to characterize postmarketing dosing failure reports involving self-injected PCSK9 inhibitors. US Food and Drug Administration Adverse Event Reporting System (FAERS) [2016-second quarter of 2023] data were utilized for a disproportionality analysis. Eight self-injected comparator medications served as referents. Medical Dictionary for Regulatory Activities preferred terms indicating explicit or probable failure to administer a complete dose classified cases. Proportional reporting ratios (PRRs) > 2.0 and lower 95% confidence intervals (CIs) > 1.0 indicated disproportionality signals. US FDA Manufacturer and User Facility Device Experience (MAUDE) [2013-2023] data underwent a narrative review. During the study period, 194,781 (evolocumab, n = 152,831; alirocumab, n = 41,950) drug-event pairs and 43,725 (evolocumab, n = 38,489; alirocumab, n = 5236) cases reported to FAERS identified PCSK9 inhibitors. MAUDE contained six evolocumab reports, half describing dose omission, and no alirocumab reports. A potential dosing failure signal was detected for evolocumab (PRR 2.01; 95% CI 1.98-2.03), but not alirocumab (PRR 0.99; 95% CI 0.97-1.02), relative to pooled comparator reports. Across three case term subcategories, incomplete dosing disproportionality signals were further identified for evolocumab patient usage complication terms (PRR 3.44; 95% CI 3.38-3.50) and alirocumab device malfunction terms (PRR 2.09; 95% CI 1.98-2.22). Proprotein convertase subtilisin kexin type 9 inhibitor incomplete dosing-related complications are frequently reported in the postmarketing setting. Systematic efforts to understand the incidence and mechanisms of dosing failure and associated patient burdens are needed.

Comparative analysis of Keynote522 treatment outcomes in Hispanic versus non-Hispanic patients with breast cancer: A single tertiary center experience.

e12661 Background: The addition of pembrolizumab to neoadjuvant chemotherapy on the Keynote522 (KN522) clinical trial, changed the standard of care for early stage triple negative breast cancer (TNBC). This regimen demonstrated longer event free survival and higher percentage of patients with pathologic complete responses (pCR). However, limited data exist on the comparative outcomes between Hispanic and non-Hispanic patients in real-world settings as this patient population was likely underrepresented on the original trial. Methods: We conducted a retrospective analysis of patients with early stage TNBC treated on KN522 regimen and undergoing surgery at a single tertiary center from July 2021 to present. Patients were stratified into Hispanic and non-Hispanic ethnicity cohorts. The primary endpoint was pCR rate, and secondary endpoints was incidence of adverse effects (AEs). Results: Among a cohort of 41 patients identified, 26 (63%) were of Hispanic and 15 (37%) were non-Hispanic. The pCR rate was 50% among Hispanic and 53% among non-Hispanic patients (p=0.83). Hispanic patients experienced higher rates of anemia (88% vs. 67%, p=0.06), fatigue (85% vs. 60%, p=0.07), skin rash (46% vs. 27%, p=0.21), and endocrine toxicities (23% vs. 13%, p=0.21). However, Hispanic patient also had fewer hospitalizations (35% vs. 47%, p=0.44), dose-modifications (12% vs. 40%, p=0.53), dose omissions (19% vs. 33%, p=0.31), and showed higher KN522 completion rates (81% vs. 53%, p=0.06). Conclusions: Our findings indicate a comparable pCR rate between Hispanic and non-Hispanic patients with early-stage TNBC receiving KN522 therapy. While Hispanic patients exhibited higher incidences of certain adverse effects, they demonstrated lower rates of hospitalizations, dose modifications, and omissions, alongside a notably higher completion rate of the KN522 regimen. These trends may be attributed to various factors such as genetic predispositions, and potentially differential physiological responses to therapy within this ethnic group. These findings underscore the importance of including minorities, such as Hispanic patients, in clinical trial populations to ensure that treatment outcomes are representative of diverse patient demographics. [Table: see text]

Treatment modifications and mortality among female patients with subsequent breast cancer: A report from the Childhood Cancer Survivor Study (CCSS).

10026 Background: Childhood cancer survivors are at high risk for developing subsequent breast cancer with higher mortality than females in the general population with primary breast cancer. Whether therapeutic tradeoffs in treating primary versus subsequent breast cancer alter survival is unknown. Methods: Breast cancer treatment data were abstracted from medical records for female survivors from the CCSS and a multi-institutional sample of females with primary breast cancer matched one-to-one by demographics, diagnosis age/year, and breast cancer characteristics. Survivors’ excess mortality risk was evaluated as hazard ratios (HRs), adjusting for receipt of historically-appropriate guideline-concordant treatment established for primary breast cancer. Results: Subsequent breast cancers were diagnosed between 1981-2016 among 431 survivors, with a median diagnosis age of 40 years (IQR: 35-44). Most subsequent breast cancers were invasive (77%), with hormone receptor profiles similar to the general population (78% ER-positive; 26% HER2-positive). Guideline-concordant breast cancer treatment did not differ between survivors and controls (N = 688; 94% versus 93%), but treatment selection differed, reflecting survivors’ complex clinical history and guidelines’ multiple treatment options. Anthracyclines were used in 47% of survivors (controls 66%), mastectomy in 81% of survivors (controls 60%), and radiotherapy in 18% of survivors (controls 61%). In the subgroup treated with surgery and chemotherapy (survivors 31%, controls 26%), survivors did not have greater likelihood of dose reductions or omissions, treatment delays, or hospitalization for fever and neutropenia, but they were more likely to experience hematological toxicities (21% vs. 9%, p = 0.033) and other organ system-specific toxicities (36% vs. 11%, p &lt; 0.001). Over one-third (38%) of survivors died during follow-up (median follow-up 9 years, IQR 6-14) after breast cancer. Strikingly higher all-cause mortality was observed among survivors than controls (HR = 3.5, 95% CI 2.2-5.6), especially after in situ disease (HR = 9.9, 95% CI 2.2-44.2). Among survivors with invasive disease, breast cancer accounted for most deaths (51%), followed by other subsequent malignancies (15%) and cardiovascular diseases (15%). Other health conditions accounted for 67% of deaths following in situ disease. Conclusions: Childhood cancer survivors with subsequent breast cancer generally receive guideline-concordant breast cancer treatment. While the treatments survivors receive differ from females with primary breast cancer, they do not experience higher rates of on-therapy treatment modifications. Despite this, they face excess mortality, primarily driven by other health conditions. Managing comorbidities is critical to enhancing long-term survival for this high-risk population.

A prospective audit on adult thromboprophylaxis and therapeutic anticoagulation prescribing and administration practices in Galway University Hospitals

Abstract Introduction Anticoagulants are high-alert medications that can cause significant patient harm if used inappropriately.[1] These preparations have been identified as a significant medication safety concern in Galway University Hospitals and are one of the most frequently reported medication incidents in Ireland.[2] A key performance indicator agreed by the local Medication Safety Subgroup and Drugs and Therapeutics Committee was to conduct an anticoagulation audit against local guidelines to identify patterns and develop quality improvements. Methods A prospective audit was conducted over six weeks from September to November 2022 by five interprofessional data collectors using a data collection tool and accessing drug records and clinical notes. Development of the tool was guided by national[1] and local guidelines as well as design input from local expert specialist doctors and pharmacists. Adult inpatients on all wards receiving thromboprophylaxis (after 24 hours of admission) or therapeutic anticoagulation were included. Paediatrics and psychiatry were excluded. The protocol and tool were approved by the local Clinical Audit Committee, piloted with three inpatients, and communicated to all data collectors prior to commencement. Generated data were anonymous and securely stored. Data analysis was carried out by two independent researchers to confirm reliability of results. Results A total of 242 inpatients were audited on 26 wards: -Patients prescribed thromboprophylaxis (52%; 126/242). -Patients prescribed therapeutic anticoagulation (26%; 63/242) -Patients not prescribed anticoagulants (22%; 54/242) Most patients (92%; 216/234) did not have a thromboprophylaxis risk assessment form completed/signed. Nineteen patients (35%; n=54) not prescribed thromboprophylaxis or therapeutic anticoagulation should have been prescribed anticoagulation. High compliance with guidelines (&amp;gt;80%) included: i) anticoagulants prescribed in correct section of drug record, ii) appropriate agents prescribed, iii) correct dose and frequency, iv) few dose delays and omissions, and v) indication mostly documented. Low compliance with guidelines (&amp;lt;35%) included: -Patient height and weight not documented: unable to calculate creatinine clearance to determine accurate dose. -Incorrect administration times for once daily therapeutic dosing (should be in morning to facilitate surgery next day) and twice daily dosing (mostly 8am and 10pm = gap of 14 hours and 10 hours). Conclusion Results have identified varying levels of compliance with local anticoagulation guidelines. To date, there has been continuous targeted education and training on appropriate anticoagulation use for doctors, nurses, and pharmacy staff inclusive of the development and implementation of a new bespoke eLearning module for high-alert medications (which includes the appropriate use of anticoagulants specific to Galway University Hospitals). High leverage strategies, such as electronic prescribing, is a current consideration to standardise practices. Strengths include study robustness, interprofessional collaboration, and transferability to other hospitals. Perhaps reducing the scope in a re-audit which will be conducted in 2024 to identify any improvements in medication safety and patient care with these agents may allow for further in-depth analysis.

Clinical outcomes of patients receiving three versus four doses of methotrexate with concomitant antithymocyte globulin in match unrelated donor allogeneic stem cell transplant: A single-center experience.

Methotrexate (MTX) doses on days +1, +3, +6, and +11 after match unrelated donor allogeneic stem cell transplant (MUD HSCT) is a common graft-versus-host disease (GVHD) prophylaxis regimen. However, the overlapping toxicity of MTX with conditioning chemotherapy sometimes warrants the omission of the fourth dose of MTX. Prior single-institution studies showed conflicting results comparing the outcomes of patients who received three versus four doses of MTX, but to our knowledge, the effect of concomitant antithymocyte globulin (ATG) has not been reported. Charts of patients who underwent MUD HSCT between 2009 and 2023 were reviewed. Patients received rabbit ATG (Thymoglobulin), given at 0.5mg/kg on day -3, 2mg/kg on day -2, and 2.5mg/kg on day -1. MTX is given at 15mg/m2 on day +1 and 10mg/m2 on days +3, +6, and +11. Severe mucositis was the most common indication for day +11 MTX omission (82%). We identified 292 patients (116 in 3 dose cohort and 176 in 4 dose cohort). Median follow-up was 23 months (range 1-151). Patients in the 4 doses cohort were more frequently male (68% vs. 50%, p<0.01), received a reduced intensity conditioning regimen (38.0% vs. 22%, p<0.01), were older (median 58 vs. 54 years, p=0.02), and received a transplant in the earlier era (median HSCT year 2014 vs. 2018, p<0.01). A statistically significant difference was not evidenced between the cohorts for the following outcomes: acute GVHD (aGVHD) (HR 1.1, 95% CI 0.9-1.5), chronic GVHD (cGVHD) (HR 1.3, 95% CI 0.8-1.6), relapse-free survival (RFS) (HR 1.0, 95% CI 0.6-1.5), non-relapse mortality (NRM) (HR 1.4, 95% CI 0.9-2.2), and overall survival (OS) (HR 1.2, 95% CI 0.9-1.7). Both cohorts had similar median time to neutrophil engraftment at 14 days. When ATG is incorporated, omission of day +11 MTX does not significantly impact the rate of engraftment or cumulative incidence of aGVHD, cGVHD, RFS, NRM, and OS.

Evaluation of Medication Errors and Prevention Strategies in a Selected Tertiary Care Hospital

A medication error is defined as a deviation from the physician’s medication order as written on the patient’s chart. Evaluation of medication errors and the implementation of prevention strategies are necessary to ensure patient safety and improve healthcare outcomes. Prospective and observational study was conducted on 218 patients, 50 (22.9%) reported medication error with 56% females and 44% males. Most of the patients included in the study were in the age group between 18 to 65 years (72%). The most common co-morbidity in patients was hypertension (27.94%). In the study, the most common category of harm is Category D (35.29%), followed by Category A (19.6%), Category F (17.64%), Category E (9.8%), Category B (7.84%), Category C (5.88%), and the least common category of harm was Category I (3.92%) based on NCC MERP guidelines. The most specific reported error was wrong dose either strength or frequency (25.84%). Prescription error 34(68%) was the most common type of error reported based on CHCF guidelines. Comparing the wards in which errors were made, (42%) occurred in the female ward. Categorizing the severity of the effect of error found, 38% patient needs monitoring, 20% patient were not harmed, 18% patients required more hospitalization time, 10% patient required treatment, 10% of the patients were not affected, and 4% of the patient died. After implementing the prevention strategies, prescription errors were prevented but other errors (Dose omission, Multi-dose) were reduced from 20% to 10%.

Estimands in Oncology Early Clinical Development: Assessing the Impact of Intercurrent Events on the Dose-Toxicity Relationship

The R1 addendum to ICH E9 (E9-R1) provides guidance on the definition of estimands in clinical drug development. While the E9-R1 has seen uptake in randomized late-stage clinical trials, its implementation in early clinical development remains sporadic potentially jeopardizing clarity, consistency, and coherency in early phase. In this article, we call for a more systematic use of the estimand thinking in phase 1 dose escalation oncology trials. In these adaptive trials, the primary clinical objective is usually to characterize the dose-toxicity relationship and to ascertain the maximum tolerated dose (MTD). One estimand of interest is the probability of dose-limiting toxicity (DLT). Intercurrent events (ICE) interfering with the existence or interpretation of DLT outcomes are common in these studies. Three types of ICEs are reviewed in detail: treatment discontinuation for reasons not related to toxicity (e.g., disease progression), treatment discontinuation due to adverse events which would not qualify as DLT, and dose modifications or omissions. The concept of replacement of non-DLT evaluable participants, often used so far, is not an acceptable general solution to ICEs in dose escalation studies. To address clinically relevant questions, adequate ICE handling strategies and estimators aligned to these settings should be used.

Real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes in Spain: The Dapa-ON multicenter retrospective study

ObjectiveTo assess real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes mellitus (T1DM). MethodsWe conducted a multicenter retrospective study in Spain including data from 250 people living with T1DM receiving dapagliflozin as add-on therapy to insulin (80.8 % on-label use). The number of diabetic ketoacidosis (DKA) events was calculated over a 12-month follow-up (primary outcome). Changes in body weight, HbA1c, total daily insulin dose, and continuous glucose monitoring (CGM) metrics from baseline (at dapagliflozin prescription) to 12 months were also evaluated. ResultsA total of five DKA events (2.4 % [95 % CI 0.3;4.5] were reported in patients with a 12-month follow-up, n = 207): two events related to insulin pump malfunction, two events related to concomitant illnesses, and one event related to insulin dose omission. DKA events were more frequent among insulin pump users than among participants on multiple daily injections (7.7 % versus 1.2 %). Four of the reported DKA events occurred within the first six months after initiation of dapagliflozin. No deaths or persistent sequelae due to DKA were reported. No severe hypoglycemia episodes were reported. Significant reductions in mean body weight (−3.3 kg), HbA1c (−0.6 %), and total daily insulin dose (−8.6 %), P < 0.001, were observed 12 months after dapagliflozin prescription. Significant improvements in TIR (+9.3 %), TAR (−7.2 %), TBR (−2.5 %), and coefficient of variation (−5.1 %), P < 0.001, were also observed in the subgroup of patients with available CGM data. Finally, an improvement in urinary albumin-to-creatinine ratio (UACR) was found among participants with UACR ≥ 30 mg/g at baseline (median decrease of 99 mg/g in UACR, P = 0.001). ConclusionThe use of dapagliflozin in people living with T1DM has an appropriate safety profile after careful selection of participants and implementation of strategies to reduce the risk of DKA (i.e., prescribed according to the recommendations of the European Medicines Agency), and also leads to clinical improvements in this population.

Activity and Event-Free Survival in Intermediate Grade Non-Hodgkin's Lymphoma Treated with Chemoimmunotherapy Utilizing Single Dose Intravenous Methylprednisolone in Lieu of Oral Prednisone

Schein et al first noted that patients with intermediate grade lymphoma treated with combination chemotherapy leading to complete response lasting 24 months were likely to remain relapse-free (Schein, Chabner, Canellos, Young, Berard, DeVita,1975). Subsequent changes in that original C-MOPP regimen have included the use of anthracyclines and rituximab. The University of Iowa/Mayo Clinic Molecular Epidemiology Resource and the Groupe d'Etude des Lymphomes de l'Adulte (GELA) program found that patients with diffuse large B-cell lymphoma achieving event-free status at 24 months with chemoimmunotherapy have subsequent overall survival equivalent to that of the general population (Maurer, 2014). While Rituximab, Cyclophosphamide, Hydroxydaunorubicin [doxorubicin], Oncovin [vincristine] and Prednisone (RCHOP) has served as the reference therapy for intermediate grade non-Hodgkin's lymphoma for two decades (Coiffier, 2002; Pfreundschuh, 2006), oral prednisone given daily for 5 days is problematic for individuals with underlying medical conditions such as diabetes, sleep or psychiatric disorders, or gastrointestinal symptoms. In this retrospective study between January, 2007 and March, 2023, 33 patients with intermediate grade Non-Hodgkin's Lymphoma, (26 with Diffuse Large B-cell subtype, 6 with follicular grade III, 1 with T-cell Immunoblastic) received Methylprednisolone 125 mg intravenously on day 1 instead of oral prednisone for 5 days as part of anthracycline-based treatment that consisted of rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 2 mg (total dose) all given intravenously on day 1 with peg-filgastrim 6 mg subcutaneously on day 2 every 21 days. Three patients received mitoxantrone 12 mg/m2 intravenously on day 1 instead of doxorubicin. Patient characteristics: 23 males/10 females, median age-55 (range: 24-85), stages: IV (17 patients), III (4 patients), II (12 patients), B symptoms (16), subtypes: non-germinal center (13), germinal center (12), diffuse B-cell NOS (1), follicular grade III (6), T-cell Immunoblastic (1). Median cycles received (range): 6 (5-8). No patients required dose reduction or omission of methylprednisolone. Complete responses (determined by PET/CT) occurred in 26 (81%). 1 additional patient was PET negative but was lost to follow-up and is not counted as CR here. Three patients having PR after chemoimmunotherapy were converted to CR after involved site radiation. Two other patients achieved only short-lived PR. One patient is too early to evaluate. The median event-free survival has not been reached at 24.8+ months. Median overall survival exceeds 32.6+ months. Chemoimmunotherapy with the substitution of intravenous methylprednisolone on day 1 in place of 5 days of oral prednisone displays activity in intermediate-grade non-Hodgkin lymphoma and event-free survival beyond 24 months.

Factores asociados al fracaso virológico en pacientes VIH con tratamiento antirretroviral

ObjectiveTo determine the factors associated with virologic failure in HIV patients on antiretroviral treatment treated in a Colombian health institution. MethodThis was a cross-sectional observational retrospective analytical study of HIV patients receiving antiretroviral treatment between 2007-2020. Sociodemographic, pharmacological and clinical variables were collected, including viral load, adherence, and the medication possession ratio. For statistical analysis, crude and adjusted odds ratios and confidence intervals were obtained. ResultsIn a population of 5,406 patients, the proportion of virologic failure was 16.7%. Moreover, in the adjusted model, an association was found between virologic failure and time on treatment greater than one year, medication possession ratio under 80%, failure to claim medications from the pharmacy due to dose omission or discontinuation, adherence under 85%, CD4 count under 500, total cholesterol levels above 201 mg/dL, high density lipoproteins under 39 mg/dL and presence of mycosis. ConclusionsIn our cohort of HIV patients, short treatment periods, CD4 counts under 200, a low medication possession ratio, failure to timely claim medications from the pharmacy due to omission or discontinuation, and a lower degree of adherence were factors related to virologic failure.

Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma

AbstractIn the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.

Statistical Analysis of Two-Compartment Pharmacokinetic Models with Drug Non-adherence.

Poor drug adherence is considered one of major barriers to achieving the clinical and public health benefits of many pharmacotherapies. In the current paper, we aim to investigate the impact of dose omission on the plasma concentrations of two-compartment pharmacokinetic models with two typical routes of drug administration, namely the intravenous bolus and extravascular first-order absorption. First, we reformulate the classical two-compartment pharmacokinetic models with a new stochastic feature, where a binomial random model of dose intake is integrated. Then, we formalize the explicit expressions of expectation and variance for trough concentrations and limit concentrations, with the latter proved of the existence and uniqueness for steady-state distribution. Moreover, we mathematically demonstrate the strict stationarity and ergodicity of trough concentrations as a Markov chain. In addition, we numerically simulate the impact of drug non-adherence to different extents on the variability and regularity of drug concentration and compare the drug pharmacokinetic preference between one and two compartment pharmacokinetic models. The results of sensitivity analysis also suggest the drug non-adherence as one of the most sensitive model parameters to the expectation of limit concentration. Our modelling and analytical approach can be integrated into the chronic disease models to estimate or quantitatively predict the therapy efficacy with drug pharmacokinetics presumably affected by random dose omissions.

Artículo traducido] Conciliación de la medicación en el alta desde la unidad de cuidados intensivos a la planta de hospitalización

ObjectivesThe aim of this study was to determine whether the transition of care from the intensive care unit to the ward would pose a high risk for reconciliation errors. The primary outcome of this study was to describe and quantify the discrepancies and reconciliation errors. Secondary outcomes included classification of the reconciliation errors by type of medication error, therapeutic group of the drugs involved and grade of potential severity. MethodsWe conducted a retrospective observational study of reconciliated adult patients discharged from the Intensive Care Unit to the ward. Before a patient was discharged from the intensive care unit, their last intensive care unit’s prescriptions were compared with their proposed medication list in the ward. The discrepancies between these were classified as justified discrepancies or reconciliation errors. Reconciliation errors were classified by type of error, potential severity, and therapeutic group. ResultsWe found that 452 patients were reconciliated. At least one discrepancy was detected in 34.29% (155/452), and 18.14% (82/452) had at least one reconciliation errors. The most found error types were a different dose or administration route (31.79% [48/151]) and omission errors (31.79% [48/151]). High alert medication was involved in 19.20% of reconciliation errors (29/151). ConclusionsOur study shows that intensive care unit to non-intensive care unit transitions are high-risk processes for reconciliation error. They frequently occur and occasionally involve high alert medication, and their severity could require additional monitoring or cause temporary harm. Medication reconciliation can reduce reconciliation errors.

Medication errors and associated factors as perceived by nurses working at the national referral hospital in Bhutan

Introduction: A common patient safety issue is medication error and this has remained a serious problem in hospital settings. Medication error occurs at any point of medication process: prescription, transcription, dispensing, and administration. Administration error is the most common type of error occurring among nurses; although nurses play a vital role in preventing harms of prescription and dispensing errors from reaching the patient. Therefore, this study was aimed at assessing medication errors and associated factors as perceived by nurses. Methods: The study was conducted at a tertiary hospital in Bhutan and 225 nurses participated through self-reported questionnaire. Data were double entered and validated in Epidata and analyzed using descriptive commands of statistical software STATA. Results: Among total participants of N = 225, 62.7% reported to have experienced medication error in past six months. Common type of error experienced were omission of dose; wrong time; wrong dose, and administering drugs without physician’s order. Nurses in intensive care units and those caring for pediatric patients reported experiencing more errors. The perceived factors were look-alike drugs, many patients with similar medicines, more medicines to single patient, and oral instructions and acronyms in prescription. Conclusions: The nurses reported to have experienced quite a high rate of medication error. The results may be used by relevant stakeholders in preventing and reducing medication errors, the biggest challenge of patient safety in hospital settings.