Liquid antimicrobials: a national analysis of critical shortages.

Medicine shortages, especially those involving antibiotics, pose a global public health dilemma that can lead to adverse health outcomes. The aim of this study was to assess the supply situation of various antimicrobials in liquid dosage forms, which represent the mainstay of therapy for paediatric infections. The availability was examined over a period of 27 weeks in Austria. During the time period investigated, 34 products (81.0%) were not available for over 50% of the time; eight of those (19.0%) experienced complete unavailability. Only four products (9.5%) demonstrated continuous availability. Regarding penicillin antibiotics, amoxicillin was not available for 77.8% of the time (21 weeks) and amoxicillin/clavulanic acid for 59.3% (16 weeks). Regular monitoring of availability status can help mitigate this issue; however, cross-national strategies are urgently needed to guarantee a constant supply in the future.

Quality assurance standards and their use in the preparation of parenteral systemic anticancer therapy products in healthcare establishments: a scoping review.

OBJECTIVES: The use of parenteral systemic anticancer therapy (SACT) has led to improved cancer survival. A quality assurance (QA) system of the aseptic compounding process is necessary to ensure safe and consistent production of parenteral SACT. This scoping review identifies international evidence and practice relating to QA standards in the preparation of parenteral SACT in healthcare establishments. METHODS: Standards relating to aseptic compounding in hospital pharmacies and literature exploring the aseptic compounding of parenteral SACT were included. Literature relating to the non-aseptic compounding of medicines and records specific to sterile manufacturing in industrial settings were excluded. A search of several electronic databases, trial registries, the grey literature and websites of key European hospital pharmacy groups and accreditation bodies was conducted on 16 March 2022. A narrative discussion was performed by country, and content analysis of articles was conducted. RESULTS: Thirty-seven records were included. Standards reviewed covered the work environment, the preparation process and the safety of the workers who are potentially exposed to hazardous chemicals. It was a common practice to include frequent audits to ensure adherence to standards. Some standards also recommended external inspections to allow for further learnings. Periodic reviews are encouraged to ensure standards maintain relevance. National standards of the countries reviewed were based on international standards, with minor adaptations for local conditions. CONCLUSIONS: The main limitation of this review is that it is limited to countries with a high human development index. The review shows that the use of an internationally recognised standard as a basis for national standards is best practice, and will allow for relevance into the future.

A Systems Approach for Assessing Low Back Pain Care Quality in Veterans Health Administration Chiropractic Visits: A Cross-Sectional Analysis.

OBJECTIVE: The purpose of this study was to explore a systemwide process for assessing components of low back pain (LBP) care quality in Veterans Health Administration (VHA) chiropractic visits using electronic health record (EHR) data. METHODS: We performed a cross-sectional quality improvement project. We randomly sampled 1000 on-station VHA chiropractic initial visits occurring from October 1, 2017, to September 30, 2018, for patients with no such visits within the prior 12 months. Characteristics of LBP visits were extracted from VHA national EHR data via structured data queries and manual chart review. We developed quality indicators for history and/or examination and treatment procedures using previously published literature and calculated frequencies of visits meeting these indicators. Visits meeting our history and/or examination and treatment indicators were classified as "high-quality" visits. We performed a regression analysis to assess associations between demographic/clinical characteristics and visits meeting our quality criteria. RESULTS: There were 592 LBP visits identified. Medical history, physical examination, and neurologic examination were documented in 76%, 77%, and 63% of all LBP visits, respectively. Recommended treatments, such as any manipulation, disease-specific education/advice, and therapeutic exercise, occurred in 75%, 69%, and 40% of chronic visits (n = 383), respectively. In acute/subacute visits (n = 37), any manipulation (92%), manual soft tissue therapy (57%), and disease-specific advice/education (54%) occurred most frequently. Female patients and those with a neck pain comorbid diagnosis were significantly less likely to have a "high-quality" visit, while other regression associations were non-significant. CONCLUSION: This study explored a systemwide process for assessing components of care quality in VHA chiropractic visits for LBP. These results produced a potential framework for uniform assessment of care quality in VHA chiropractic visits for LBP and highlight potential areas for improvements in LBP care quality assessments.

Measuring in-hospital quality multidimensionally by integrating patients', kin's and healthcare professionals' perspectives: development and validation of the FlaQuM-Quickscan.

BACKGROUND: Measuring quality is essential to drive improvement initiatives in hospitals. An instrument that measures healthcare quality multidimensionally and integrates patients', kin's and professionals' perspectives is lacking. We aimed to develop and validate an instrument to measure healthcare quality multidimensionally from a multistakeholder perspective. METHODS: A multi-method approach started by establishing content and face validity, followed by a multi-centre study in 17 Flemish (Belgian) hospitals to assess construct validity through confirmatory factor analysis, criterion validity through determining Pearson's correlations and reliability through Cronbach's alpha measurement. The instrument FlaQuM-Quickscan measures 'Healthcare quality for patients and kin' (part 1) and 'Healthcare quality for professionals' (part 2). This bipartite instrument mirrors 15 quality items and 3 general items (the overall quality score, recommendation score and intention-to-stay score). A process evaluation was organised to identify effective strategies in instrument distribution by conducting semi-structured interviews with quality managers. RESULTS: By involving experts in the development of quality items and through pilot testing by a multi-stakeholder group, the content and face validity of instrument items was ensured. In total, 13,615 respondents (5,891 Patients/kin and 7,724 Professionals) completed the FlaQuM-Quickscan. Confirmatory factor analyses showed good to very good fit and correlations supported the associations between the quality items and general items for both instrument parts. Cronbach's alphas supported the internal consistency. The process evaluation revealed that supportive technical structures and approaching respondents individually were effective strategies to distribute the instrument. CONCLUSIONS: The FlaQuM-Quickscan is a valid instrument to measure healthcare quality experiences multidimensionally from an integrated multistakeholder perspective. This new instrument offers unique and detailed data to design sustainable quality management systems in hospitals. Based on these data, hospital management and policymakers can set quality priorities for patients', kin's and professionals' care. Future research should investigate the transferability to other healthcare systems and examine between-stakeholders and between-hospitals variation.

One-step embedding method for maintaining orientation of pathological tissue specimens using agar thin films.

Pathological histology examination involves handling a variety of specimens that are cut according to regulations and placed in cassettes. Tissue fragments in the cassettes are then diagnosed after processing, embedding, thin sectioning, staining and other procedures using a processing machine. Maintaining tissue fragment order and orientation during these processes is important for accurate diagnosis. In this study, we present a method of maintaining tissue fragment order and orientation using a thin film of ultra-high-strength agar and evaluate its usefulness during tissue sectioning.Cassettes were prepared, each containing three pieces of porcine liver, and compared embedding time with and without agar thin films (ATFs). Embedding was performed by three medical laboratory scientists with different levels of experience.To enable one-step tissue sample embedding, ATFs were integrated with samples in the cassettes. This resulted in an average reduction of 6.22 s of embedding time per cassette compared with traditional embedding methods.Through the use of ATFs, tissue fragment order and orientation is maintained, and embedding process time shortened. Additionally, ATFs are easily prepared and stored in 10% neutral buffered formalin over extended periods, allowing for immediate use during sectioning. This method is ideal to implement in busy pathology laboratories.

A pilot study of half-value layer measurements using a semiconductor dosimeter for intraoral radiography.

Purpose: This pilot study was conducted to evaluate half-value layer (HVL) measurements obtained using a semiconductor dosimeter for intraoral radiography. Materials and Methods: This study included 8 aluminum plates, 4 of which were low-purity (less than 99.9%) and 4 high-purity (greater than 99.9%). Intraoral radiography was performed using an intraoral X-ray unit in accordance with the dental protocol at the authors' affiliated hospital: tube voltage, 60 kVp and 70 kVp; tube current, 7 mA; and exposure time, 0.10 s. The accuracy of HVL measurements for intraoral radiography was assessed using a semiconductor dosimeter. A simple regression analysis was performed to compare the aluminum plate thickness and HVL in relation to the tube voltage (60 kVp and 70 kVp) and aluminum purity (low and high). Results: For the low-purity aluminum plates, the HVL at 60 kVp (Y) and 70 kVp (Y) was significantly correlated with the thickness of the aluminum plate (X), with Y = 1.708 + 0.415X (r=0.999, P<0.05) and Y = 1.980 + 0.484X (r=0.999, P<0.05), respectively. Similarly, for the high-purity aluminum plates, the HVL at 60 kVp (Y) and 70 kVp (Y) was significantly correlated with the plate thickness (X), with Y = 1.696 + 0.454X (r=0.999, P<0.05) and Y = 1.968 + 0.515X (r=0.998, P<0.05), respectively. Conclusion: This pilot study examined the relationship between aluminum plate thickness and HVL measurements using a semiconductor dosimeter for intraoral radiography. Semiconductor dosimeters may prove useful in HVL measurement for purposes such as quality assurance in dental X-ray imaging.

Understanding the biases to sepsis surveillance and quality assurance caused by inaccurate coding in administrative health data.

PURPOSE: Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. METHODS: We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015-2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. RESULTS: ICD-coding of sepsis in IAHD showed high positive predictive value (76.9-85.7% depending on sepsis definition), but low sensitivity (26.8-38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29-71.7%, of ICD-diagnosis: 10.7-58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09). CONCLUSION: Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care.

Stability assessment and content determination test of oral liquid forms of beclomethasone dipropionate prepared in hospital pharmacy.

OBJECTIVES: Oral beclomethasone dipropionate (BDP) is known for its use as a therapeutic medicine for gastrointestinal graft-versus-host disease (GI-GVHD). Despite growing demand for oral BDP formulation, no commercial forms have yet been marketed. Therefore, at the Tokyo Metropolitan Cancer and Infectious Disease Centre Komagome Hospital, pharmacists prepare oral liquid forms of BDP for patients with upper GI-GVHD. This study aims to develop a new high performance liquid chromatography (HPLC) method for measuring BDP in the prepared formulations and assessing its quality. METHODS: We developed a new HPLC method for measuring BDP in prepared formulations validated according to international guidelines. Three types of formulations were prepared and analysed using the validated HPLC method. One contains 1 mg of BDP per 30 mL aqueous solution, and the others using ethanol for preparation contain 1 mg of BDP per 15 mL aqueous solution. For stability assessment, the BDP contents were assayed while formulations were stored in plastic bottles for 8 weeks under two different conditions of 25°C in bright light and 4°C in darkness. A content determination test was also conducted to assess the individual contents of BDP and lot-to-lot variation in dosage units. RESULTS: A stability test demonstrated that the remaining BDP content after the storage period was greater than 90% of the initial content in almost all samples regardless of storage conditions. A content determination test showed thattwo new ethanol-containing formulations contained about 0.1 mg more BDP than the original ethanol-free formulation and it was close to the target BDP content of 1 mg. Furthermore, new formulations had less lot-to-lot BDP variation in dosage units than the original formulation. CONCLUSIONS: A new HPLC method for measuring BDP in prepared formulations was developed and validated. The results of the stability test and content determination test indicated that the newly designed formulations were superior to the conventional formulation.

Activating pharmacists to reduce the frequency of medication-related problems (ACTMed): a stepped wedge cluster randomised trial.

BACKGROUND: Medicines are the most frequent health care intervention type; their safe use provides significant benefits, but inappropriate use can cause harm. Systemic primary care approaches can manage serious medication-related problems in a timely manner. OBJECTIVES: ACTMed (ACTivating primary care for MEDicine safety) uses information technology and financial incentives to encourage pharmacists to work more closely with general practitioners to reduce the risk of harm, improve patients' experience of care, streamline workflows, and increase the efficiency of medical care. METHODS AND ANALYSIS: The stepped wedge cluster randomised trial in 42 Queensland primary care practices will assess the effectiveness of the ACTMed intervention. The primary outcome will be the proportion of people at risk of serious medication-related problems - patients with atrial fibrillation, heart failure, cardiovascular disease, type 2 diabetes, or asthma or chronic obstructive pulmonary disease - who experience such problems. We will also estimate the cost per averted serious medication-related problem and the cost per averted potentially preventable medication-related hospitalisation. ETHICS APPROVAL: The University of Queensland Human Research Ethics Committee approved the pilot (2021/HE002189) and trial phases of the ACTMed study (2022/HE002136). Access to Patron data was granted by the Patron Data Governance Committee (PAT052ACTMed). Access to linked hospitalisations and deaths data are subject to Public Health Act approval (pending). DISSEMINATION OF FINDINGS: A comprehensive dissemination plan will be co-developed by the researchers, the ACTMed steering committee and consumer advisory group, project partners, and trial site representatives. Aboriginal and Torres Strait Islander communities will be supported in leading community-level dissemination. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (pilot: ACTRN12622000595718; 21 April 2022; full trial: ACTRN12622000574741; 14 April 2022).

The Patient-Centered Dental Home: A Framework for Quality Measurement, Improvement, and Integration.

OBJECTIVE: This study completed the development of a standardized patient-centered dental home (PCDH) framework to align and integrate with the patient-centered medical home. This study identified measure concepts and specific measures and standards to complete the 4-level measurement framework to implement and evaluate a PCDH. This study built on prior model development, which identified the PCDH definition and characteristics and the components nested within those characteristics. METHODS: An environmental scan identified existing oral health care quality measure concepts, measures, and standards for rating by the project's National Advisory Committee (NAC). A modified Delphi process, adapted from the RAND appropriateness method, was used to obtain structured feedback from the NAC. NAC members rated measure concepts on importance and, subsequently, specific measures and standards on feasibility, validity, and actionability using a 1 to 9 rating scale. Criteria for model inclusion were based on median ratings and rating dispersion. Open-ended comments were elicited to inform model inclusion as well as identify additional concepts. RESULTS: We identified more than 500 existing oral health care measures and standards. A structured process was used to identify a subset that best aligned with a PCDH for rating by the NAC. Four Delphi rounds were completed, with 2 rounds to rate measure concepts and 2 rounds to rate measures and standards. NAC quantitative ratings and qualitative comments resulted in a total of 61 measure concepts and 47 measures and standards retained for inclusion in the framework. CONCLUSIONS: The NAC ratings of measure concepts, and specific measures and standards nested within those concepts, completed the 4-level PCDH measurement framework. The resulting framework allows for the development and implementation of core measure sets to identify and evaluate a PCDH, facilitating quality improvement and dental-medical integration. KNOWLEDGE TRANSFER STATEMENT: Clinicians, payers, health care systems, and policy makers can use the results of this study to guide and assess implementation of the various components of a patient-centered dental home and to support dental-medical integration.

First Provider Seen for an Acute Episode of Low Back Pain Influences Subsequent Health Care Utilization.

OBJECTIVE: Costs associated with low back pain (LBP) continue to rise. Despite numerous clinical practice guidelines, the evaluation and treatments for LBP are variable and largely depend on the individual provider. As yet, little attention has been given to the first choice of provider. Early research indicates that the choice of first provider and the timing of interventions for LBP appear to influence utilization. We sought to examine the association between the first provider seen and health care utilization. METHODS: Using 2015-2018 data from a large insurer, this retrospective analysis focused on patients (29,806) seeking care for a new episode of LBP. The study identified the first provider chosen and examined the following year of medical utilization. Cox proportional hazards models were calculated using inverse probability weighting on propensity scores to evaluate the time to event and the relationship to the first choice of provider. RESULTS: The primary outcome was the timing and use of health care resources. Total health care use was lowest in those who first sought care with chiropractic care or physical therapy. Highest health care use was seen in those patients who chose the emergency department. CONCLUSION: Overall, there appears to be an association between the first choice of provider and future health care use. Chiropractic care and physical therapy provide nonpharmacologic and nonsurgical, guideline-based interventions. The use of physical therapists and chiropractors as entry points into the health system appears related to a decrease in immediate and long-term use of health resources. This study expands the existing body of literature and provides a compelling case for the influence of the first provider on an acute episode of LBP. IMPACT: The first provider seen for an acute episode of LBP influences immediate treatment decisions, the trajectory of a specific patient episode, and future health care choices in the management of LBP.

Patterns of care for people with small cell lung cancer in Victoria, 2011-19: a retrospective, population-based registry data study.

OBJECTIVES: To report stage-specific patterns of treatment and the influence of management and treatment type on survival rates for people newly diagnosed with small cell lung cancer (SCLC). DESIGN: Cross-sectional patterns of care study; analysis of data prospectively collected for the Victorian Lung Cancer Registry (VLCR). SETTING, PARTICIPANTS: All people diagnosed with SCLC in Victoria during 1 April 2011 - 18 December 2019. MAIN OUTCOME MEASURES: Stage-specific management and treatment of people with SCLC; median survival time. RESULTS: During 2011-19, 1006 people were diagnosed with SCLC (10.5% of all lung cancer diagnoses in Victoria); their median age was 69 years (interquartile range [IQR], 62-77 years), 429 were women (43%), and 921 were current or former smokers (92%). Clinical stage was defined for 896 people (89%; TNM stages I-III, 268 [30%]; TNM stage IV, 628 [70%]) and ECOG performance status at diagnosis for 663 (66%; 0 or 1, 489 [49%]; 2-4, 174 [17%]). The cases of 552 patients had been discussed at multidisciplinary meetings (55%), 377 people had received supportive care screening (37%), and 388 had been referred for palliative care (39%). Active treatment was received by 891 people (89%): chemotherapy, 843 (84%); radiotherapy, 460 (46%); chemotherapy and radiotherapy, 419 (42%); surgery, 23 (2%). Treatment had commenced within fourteen days of diagnosis for 632 of 875 patients (72%). Overall median survival time from diagnosis was 8.9 months (IQR, 4.2-16 months; stage I-III: 16.3 [IQR, 9.3-30] months; stage IV: 7.2 [IQR, 3.3-12] months). Multidisciplinary meeting presentation (hazard ratio [HR], 0.66; 95% CI, 0.58-0.77), multimodality treatment (HR, 0.42; 95% CI, 0.36-0.49), and chemotherapy within fourteen days of diagnosis (HR, 0.68; 95% CI, 0.48-0.94) were each associated with lower mortality during follow-up. CONCLUSION: Rates of supportive care screening, multidisciplinary meeting evaluation, and palliative care referral for people with SCLC could be improved. A national registry of SCLC-specific management and outcomes data could improve the quality and safety of care.

Errors in prescribing injectable anticancer drugs: benefits of a pharmaceutical long-term monitoring to improve patient safety in a European comprehensive cancer centre.

OBJECTIVES: We aimed to assess the impact of pharmacist interventions on injectable chemotherapy prescription and the safety of early prescription practice in an adult daily care unit. METHODS: Prescription errors were recorded before and after implementing corrective measures. Errors identified from the pre-intervention period (i) were analysed to identify areas for improvement. During the post-intervention period (ii) we compared the errors in anticipated prescription (AP) with those in real-time prescriptions (RTP). We performed Chi-square statistical tests (α=0.05). RESULTS: Before implementing corrective measures (i), 377 errors were recorded (ie, 3.02% of prescriptions). After the implementation of corrective measures (ii), there was a significant decrease in errors, with 94 errors recorded (ie, 1.20% of prescriptions). The error rate in AP and RTP groups was 1.34% and 1.02%, respectively, without a significant difference between the two groups. CONCLUSIONS: This study highlights the importance of prescription review, as well as collaboration between pharmacists and physicians, in reducing prescription errors, whether these prescriptions were anticipated or not.

Building an antimicrobial stewardship program: A narrative of six years under the Donabedian perspective.

Introduction: Antimicrobial resistance (AMR) is increasing and represents one of the world's major challenges. AMR increase morbimortality, length of hospital stay and costs. Antimicrobial Stewardship Programs (ASP) are one of the key strategies to promote the rational use of antimicrobials since AMR is mostly driven by antimicrobial consumption. Objective: To describe the ASP implementation in a teaching hospital from the perspective of Donabedian quality assessment and the Brazilian regulatory requirements. Method: This was a descriptive study with secondary data collection, including document review of the ASP. The study setting was a general public 392-bed hospital. The ASP activities were performed by the hospital infection control committee (HICC), hospital pharmacy (HP) and diagnostic support laboratory (DSL). The description of the three services mainly involved in the ASP was based on a quality assessment model involving the dimensions of "structure", "process" and "result" proposed by Donabedian. The distribution among dimensions was guided by the checklist of essential elements of the ASP that compose the Brazilian regulatory requirements. The checklist was applied in July, 2022, and the ASP results described from 2016 to 2021. Results: ASP actions have been gradually implemented since 2008 with the implementation of HICC and improved over the years. Regarding structure, the investments in technology were mapped, quantifying 26 computers and three software programs employed to computerize the ASP processes performed in specific physical areas by HICC, HP and DSL. Institutional guidelines used by HICC, HP and DSL guided clinical practices to operationalize ASP. The evaluation metrics improved for 10 indicators and worsened for four indicators. From the 60 items composing the checklist, the hospital met the requirements in 73.3% of the items (n = 44). Conclusion: This study described the implementation of ASP in a teaching hospital, applying the Donabedian perspective. Although the hospital still does not have a classic ASP model, there were investments to improve structure, processes and results, aiming to comply with international guidelines. A high proportion of key elements of ASP in the hospital were followed according to the Brazilian regulatory requirements. Aspects related to antimicrobial consumption and the emergence of microbial resistance deserve further investigations.

[Clinical trials as a central part of patient-centered clinical research]. / Klinische Studien als zentraler Bestandteil patientenorientierter Forschung.

As the continuation and implementation of findings from basic (pre­)clinical research, clinical trials make a significant contribution to medical research. They form the central building block of translational medicine and thus make a decisive contribution to bringing medical knowledge into general care. This helps to make possible a healthcare system that is aligned to the needs of patients and functions efficiently in the long term. Based on the specific objective, clinical trials must comply with national, but increasingly also with European and international regulatory requirements. In academia in particular, expertise in a variety of fields is required in order to make investigator-driven clinical trials a success. This expertise can be provided by a clinical trial center based within the institution conducting the trial.

Testing of parenteral drug products for visible particles: comparison of the Ph. Eur. method with an alternative method using polarised light.

OBJECTIVES: Parenteral drug products should be essentially free from visible particulate contamination. To ensure this, every batch produced must be subject to a 100% visual inspection. Monograph 2.9.20 of the European Pharmacopoeia (Ph. Eur.) describes a method for visual inspection of parenteral drug units in front of a black and white panel using a white light source. Nevertheless, several Dutch compounding pharmacies rely on an alternative method for visual inspection by means of polarised light. The objective of this study was to compare the performance of both methods. METHODS: Trained technicians in three different hospitals inspected a predetermined set of samples using both methods for visual inspection of parenteral drugs. RESULTS: The results of this study show that the alternative method for visual inspection yields a higher recovery than the Ph. Eur. method, while no significant difference in false positive results was found. CONCLUSIONS: Based on these findings, it can be concluded that the alternative method for visual inspection by means of polarised light can very well replace the Ph. Eur. method in pharmacy practice, provided that local validation of the alternative method is performed.

Radiotherapy quality assurance in paediatric clinical trials: first report from six QUARTET-affiliated trials.

BACKGROUND AND PURPOSE: SIOP Europe's QUARTET project launched in 2016; aiming to improve access to high-quality radiotherapy for children and adolescents treated within clinical trials across Europe. The aim of this report is to present the profile of institutions participating in six QUARTET-affiliated trials and a description of the initial individual case review (ICR) outcomes. METHODS: This is a two-part analysis. Firstly, using facility questionnaires, beam output audit certificates, and advanced technique credentialing records to create a profile of approved institutions, and secondly, collating trial records for ICRs submitted prior to 31/10/2022. Trials included are: SIOPEN HR-NBL1, SIOPEN-LINES, SIOPEN- VERITAS, SIOP-BTG HRMB, EpSSG-FaR-RMS, and SIOPEN HR-NBL2. RESULTS: By 31/10/2022, a total of 103 institutions had commenced QUARTET site approval procedures to participate in QUARTET-affiliated trials; 66 sites across 20 countries were approved. These participating institutions were often paediatric referral sites with intensity modulated radiotherapy or proton beam therapy, designated paediatric radiation oncologists, and paediatric adapted facilities and imaging protocols available. In total, 263 patient plans were submitted for ICR, 254 ICRs from 15 countries were completed. ICRs had a rejection rate of 39.8%, taking an average of 1.4 submissions until approval was achieved. Target delineation was the most frequent reason for rejection. CONCLUSION: The QUARTET facility questionnaire is a valuable tool for mapping resources, personnel, and technology available to children and adolescents receiving radiotherapy. Prospective ICR is essential for paediatric oncology clinical trials and should be prioritised to reduce protocol violations.

Evaluation of the stability of temocillin in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy in accordance with the requirements of the UK NHS Yellow Cover Document.

OBJECTIVE: To evaluate the stability of temocillin solution in two elastomeric infusion devices - Easypump II LT 270-27- S and Dosi-Fusor L25915-250D1 for OPAT administration during 14 days of 5°C±3°C fridge storage followed by 24 hour exposure at an in-use temperature of 32°C, when reconstituted with 0.3% citrate buffer at pH7. METHODS: Stability testing was conducted in accordance with standard protocols in the UK National Health Service Yellow Cover Document (YCD). A stability indicating assay method was applied using a high-performance liquid chromatography (HPLC) system with a photodiode array detector. Low (500 mg/240 mL), intermediate (4000 mg/240 mL) and high (6000 mg/240 mL) temocillin concentrations were tested in triplicate devices with duplicate samples taken at 11 time points during fridge storage and subsequent in-use temperature exposure. RESULT: The percentage of temocillin remaining after 14 days of fridge storage was greater than 97% in both devices and at all concentrations tested. During subsequent in-use temperature exposure, a 95% stability limit was achieved for 12 hours except for the high concentration (25 mg/mL) in the Dosi-Fusor device. It met this criterion for only 10 hours - the percent of temocillin remaining at 12 hours was 94.5%. However, for all devices and the doses tested, the degradation of temocillin was <9% at the end of 24 hours in-use temperature exposure. CONCLUSION: Temocillin reconstituted with 0.3% citrate buffer at pH7 in elastomeric infusion devices can be stored in a fridge (2°C-8°C) for 14 days meeting the YCD acceptance criteria. Considering <5% degradation, the current data supports twice daily dosing of temocillin within the OPAT setting. In jurisdictions where a <10% degradation limit is acceptable, once daily dosing with 24-hour continuous infusion may be considered. Temocillin is a useful alternative to other broad-spectrum anti-Gram-negative agents currently utilised in the OPAT setting and supports the wider antimicrobial stewardship agenda.