The Introduction of An Intravenous Fluid Bundle to Improve the Prescribing of Intravenous Fluids Within a District General Hospital (Preprint)

BACKGROUND Intravenous (IV) fluids are some of the most commonly prescribed day-to-day drugs. Evidence suggests that such prescriptions are rarely ever done correctly despite the presence of clear guidelines (NICE CG174). This is believed to be due to lack of knowledge and experience, which often breeds confusion and places patients at increased risk of harm. It also incurs avoidable costs to hospitals. OBJECTIVE This quality improvement project (QIP) aims to ensure that IV fluid prescriptions are: safe, appropriate and adhere to evidence-based NICE guidance. The project’s aims will be achieved through implementing multiple interventions that are categorised under: educational, changing prescribing habits and raising awareness. METHODS Review and improve the prescribing process of “IV fluid prescribing” via three simultaneous approaches. Teaching sessions were delivered to all junior doctors in order to improve knowledge and awareness of appropriate IV fluid prescribing and promote familiarity with the current NICE IV fluid guidelines. This included a ‘feature session’ at our local hospital Grand Round. A point-of-care aide-memoire containing a summary of the information needed for correct prescription was designed and printed. This complimented the teaching sessions and supported good clinical practice. Using serial Plan-Do-Study-Act (PDSA) cycles, a novel “IV fluid bundle” was developed, fine-tuned and trialled on five wards, (three surgical, two medical). The aim of the bundle was to ensure that patients were clinically reviewed in order to assess their volaemic status in order that appropriate IV fluids could then be selected and prescribed safely. The impact of these interventions was assessed on the trial wards via a weekly point prevalence audit of the IV fluid bundles for the duration of the trial. Parameters looked at were: incidence of deranged U&E’s, incidence of AKI and the number of days between the latest U&E’s and the patient’s IV fluid prescription. RESULTS These interventions were assessed on trial wards via a weekly point prevalence audit of the new IV fluid prescription chart (bundle; IFB) for the duration of the trial. Parameters monitored were: incidence of deranged U&E’s, incidence of acute kidney injury (AKI) and the number of days between the latest U&E’s and the patient’s IV fluid prescription. Of all of the patients on the IV fluid bundle, 100% had a documented weight, review of both fluid status and balance. The incidence of deranged U&E’s decreased from 48% to 35%. Incidence of AKI decreased from 24% to 10%. The average number of days between the latest U&E’s and a fluid prescription decreased from 2.2 days to 0.6 day. CONCLUSIONS Prescribing IV fluids is a complex task that requires significant improvement both locally and nationally. With 85% uptake of the IFB, we were able to significantly improve all measured outcomes. Through carefully structured interventions geared towards tackling the confounding issues identified from previous audits and process mapping we have shown that prescribing IV fluids can be made safer.

Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study

Purpose Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). Methods We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. Results All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. Conclusion This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. Trial registration number www.trialregister.nl: NTR7536.

Evaluation of an enhanced training package to support clinical trials training in low and middle income countries (LMICs): experiences from the Born Too Soon Optimising Nutrition study

Background Training is essential before working on a clinical trial, yet there is limited evidence on effective training methods. In low and middle income countries (LMICs), training of research staff was considered the second highest priority in a global health methodological research priority setting exercise. Methods We explored whether an enhanced training package in a neonatal feasibility study in Kenya and India, utilising elements of the train-the-trainer approach, altered clinicians and researchers’ clinical trials knowledge. A lead “trainer” was identified at each site who attended a UK-based introductory course on clinical trials. A two-day in-country training session was conducted at each hospital. Sessions included the study protocol, governance, data collection and ICH-Good Clinical Practice (GCP). To assess effectiveness of the training package, participants completed questionnaires at the start and end of the study period, including demographics, prior research experience, protocol-specific questions, informed consent and ICH-GCP. Results Thirty participants attended in-country training sessions and completed baseline questionnaires. Around three quarters had previously worked on a research study, yet only half had previously received training. Nineteen participants completed questionnaires at the end of the study period. Questionnaire scores were higher at the end of the study period, though not significantly so. Few participants ‘passed’ the informed consent and ICH-Good Clinical Practice (GCP) modules, using the Global Health Network Training Centre pass mark of ≥ 80%. Participants who reported having prior research experience scored higher in questionnaires before the start of the study period. Conclusions An enhanced training package can improve knowledge of research methods and governance though only small improvements in mean scores between questionnaires completed before and at the end of the study period were seen and were not statistically significant. This is the first report evaluating a clinical trial training package in a neonatal trial in LMICs. Due to the Covid-19 pandemic, research activity was paused and there was a significant time lapse between training and start of the study, which likely impacted upon the scores reported here. Given the burden of disease in LMICs, developing high-quality training materials which utilise a variety of approaches and build research capacity, is critical.

Healing of periapical lesion after root canal treatment: A case report

Most of periapical lesions usually result from microbial infection with oral microorganisms originating from the degenerated pulp tissue. These lesions are commonly painless and incidentally found on routine radiographic examinations. Treating these cases using non-surgical root canal is the fruit of the innovative techniques, tools and root medicaments as well as the tendency toward minimally invasive treatment. The healing process of the infected area is conditioned by a proper diagnosis, a treatment that follows good clinical practice under aseptic environment including cleaning, shaping and root filing. The aim of the present clinical case report was to report non-surgical healing of a periapical lesion of endodontic origin associated with maxillary left central incisor, observed over a period of 2 years.

Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged ≥4 years with moderate-to-severe asthma: rationale and design of the randomised, double-blind, active-controlled MANDALA study

IntroductionUncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to address the underlying inflammation. Combining a short-acting beta2-agonist, such as albuterol (salbutamol), with an inhaled corticosteroid, such as budesonide, in a single inhaler as rescue therapy could help control both bronchoconstriction and inflammation, and reduce the risk of asthma exacerbations.Methods and analysisThe Phase 3 MANDALA study was designed to determine the efficacy of albuterol in combination with budesonide (albuterol/budesonide 180/160 µg or 180/80 µg, two actuations of 90/80 µg or 90/40 µg, respectively) versus albuterol (180 µg, two actuations of 90 µg) as rescue therapy in adult, adolescent and paediatric patients with moderate-to-severe asthma. This event-driven study enrolled symptomatic patients (3000 adults/adolescents and 100 children aged 4–11 years) who experienced ≥1 severe asthma exacerbation in the previous year and were receiving maintenance therapy for ≥3 months prior to study entry. The primary efficacy endpoint was time-to-first severe asthma exacerbation.Ethics and disseminationThe study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Good Clinical Practice and the applicable regulatory requirements.Trial registrationNCT03769090.

Hyperkalaemia prevalence, recurrence and treatment in patients on haemodialysis in China: protocol for a prospective multicentre cohort study (PRECEDE-K)

IntroductionHyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes and is common in patients with kidney failure. However, there is no evidence on the occurrence, recurrence and treatment of HK in patients on haemodialysis (HD) in China.Methods and analysisThe HK Prevalence, Recurrence, and Treatment in Haemodialysis Study is a prospective, multicentre, observational, cohort study being conducted across 15–18 sites in China. Approximately 600 patients with end-stage kidney disease on HD are anticipated to be enrolled and will be followed up for 24 weeks. Patients will be in the long interdialytic interval (LIDI) at enrolment and will receive follow-up care every 4 weeks in LIDI for pre-dialysis and post-dialysis (at enrolment only) serum potassium measurements. To obtain pre-dialysis serum potassium levels in the short interdialytic interval (SIDI), a follow-up visit will be performed in the SIDI during the first week. Information on concomitant medications, blood gas analysis and biochemistry measurements will be obtained at enrolment and at each follow-up visit. The primary endpoint will be the proportion of patients experiencing HK (defined as serum potassium level >5.0 mmol/L) at the study enrolment or during the 24-week follow-up. The key secondary endpoint will be the proportion of patients experiencing HK recurrence (defined as any HK event after the first HK event) within 1–6 months (if applicable) during the 24-week follow-up, including enrolment assessment.Ethics and disseminationThis study has been approved by Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee (2020-040). Other participating subcentres must also obtain ethics committee approval prior to the start of the study. The Good Clinical Practice regulations shall be strictly followed during the test implementation. Amendments to the protocol will be reviewed by the ethics committees. Written informed consent will be obtained from all participants before collection of any patient data and patient information. The findings of this study will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberClinicalTrials.gov Registry (NCT04799067).

Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD)

IntroductionIdiopathic pulmonary fibrosis (IPF) and non-IPF, progressive fibrotic interstitial lung diseases (PF-ILD), are associated with a progressive loss of lung function and a poor prognosis. Treatment with antifibrotic agents can slow, but not halt, disease progression, and treatment discontinuation because of adverse events is common. Fibrotic diseases such as these can be mediated by lysophosphatidic acid (LPA), which signals via six LPA receptors (LPA1–6). Signalling via LPA1 appears to be fundamental in the pathogenesis of fibrotic diseases. BMS-986278, a second-generation LPA1 antagonist, is currently in phase 2 development as a therapy for IPF and PF-ILD.Methods and analysisThis phase 2, randomised, double-blind, placebo-controlled, parallel-group, international trial will include adults with IPF or PF-ILD. The trial will consist of a 42-day screening period, a 26-week placebo-controlled treatment period, an optional 26-week active-treatment extension period, and a 28-day post-treatment follow-up. Patients in both the IPF (n=240) and PF-ILD (n=120) cohorts will be randomised 1:1:1 to receive 30 mg or 60 mg BMS-986278, or placebo, administered orally two times per day for 26 weeks in the placebo-controlled treatment period. The primary endpoint is rate of change in per cent predicted forced vital capacity from baseline to week 26 in the IPF cohort.Ethics and disseminationThis study will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and local ethical and legal requirements. Results will be reported in a peer-reviewed publication.Trial registration numberNCT04308681.

Diabetes in der Schwangerschaft: Strategien inklusive Bewegungsprogramme

ZusammenfassungBei etwa jeder neunten Schwangeren wird im Verlauf der Schwangerschaft ein Gestationsdiabetes diagnostiziert. Das Screeningprogramm gehört zur GCP („good clinical practice“) und wird weit verbreitet angewandt. Nach der Diagnose sind viele Frauen verunsichert und sind dankbar für Instruktionen, da sie beim Gestationsdiabetes vieles selbst beeinflussen können. Im Beitrag werden die möglichen Interventionen vorgestellt.

Appendiceal Mucocele - A Review of Literature with a Case Report

Background: Appendiceal mucoceles represent neoplastic and non-neoplastic, dilatated, mucus filled appendix vermiformix. Appendectomy is obligatory due to a possible malignancy. It is crucially important to avoid rupturing of the mucocele because it can result in pseudomyxoma peritonei, with high morbidity and mortality. Case Report: We presented a 52-year-old man with pain and palpable mass in the lower right quadrant of the abdomen. The mucocele was removed without a rupture, and the patient was discharged from the surgical department one day after the surgery without a complication. Discussion: The resection must be done very carefully, because the rupture of a mucocele can cause pseudomyxoma peritonei, a very dangerous and often lethal condition. Due to the concern of rupture, we performed the classical resection through laparotomy. Conclusion: It is very important, especially for young, inexperienced surgeons to be aware of this rare diagnosis and perform a surgical intervention according to the guidelines of good clinical practice.

Survey Results and Recommendations from Japanese Stakeholders for Good Clinical Practice Renovation

Background The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is undertaking a major revision of ICH E6 Good Clinical Practice (GCP) decided to involve external stakeholders in ICH-GCP renovation. Activities such as surveys and public conferences have taken place in the United States, European Union, and Japan. For stakeholder engagement in Japan, a designated research group conducted a survey of academic stakeholders. Methods A total of 105 academic stakeholders from 18 institutions responded to the survey. The research group developed recommendations reflecting the survey results and the opinions from patients and the public. Results The survey showed the top four principles needing renovation were (i) informed consent (Chapter 2.9, 12.4% of respondents believed it needed renovation), (ii) systems for quality assurance (Chapter 2.13, 9.5%), (iii) information on an investigational product (Chapter 2.4, 5.7%), and (iv) procedures on clinical trial information (Chapter 2.10, 5.7%). The top three sections identified as needing renovation were: (i) informed consent (Chapter 4.8, 27.6%), (ii) monitoring (Chapter 5.18, 22.9%), and (iii) composition, functions, and operations of the ethics committee (Chapter 3.2, 14.3%). Recommendations included clarification of ICH-GCP’s scope, proportionality in various aspects of clinical trials, diversity and liquidity of ethics committee members, modernization of informed consent procedures, variations in monitoring, and regulatory grade when using real-world data. Conclusion The recommendations from Japanese investigators and patients have been submitted to the ICH E6 Expert Working Group, which will strengthen the robustness of the GCP renovation.