Clinical Unit Research Articles

PSUN111 Rationale and Design of the Dinner Time 2 Trial: A Randomized, Crossover Trial to Compare the Effects of Delayed Eating vs Delayed Sleeping on Overnight Metabolism in Healthy Volunteers

Abstract Background Obesity and its associated metabolic complications are leading causes of morbidity and mortality worldwide. Recent studies suggest that the timing of meals may be critically important for weight control and metabolic health. Consuming calories later in the day is associated with greater risks of obesity and metabolic syndrome. Interventional diet studies show more weight loss with early, rather than later, eating. Our team conducted a randomized, crossover study ("Dinner Time Study") that compared the metabolic effects of routine dinner (6pm) vs late dinner (10pm) with a fixed sleep period (11pm-7am) in young, healthy adults. We found that late dinner caused an 18% increase in post-prandial glucose and a 10% decrease in dietary fat oxidation. These metabolic consequences in the long term may lead to the development of obesity and type 2 diabetes. However, it remains unclear whether the adverse metabolic effects of late dinner are mediated by circadian misalignment (eating at the "wrong" time relative to the body's central circadian clock) or mediated by sleep (eating too close to bedtime, coinciding with the fall in metabolic rate induced by sleep). To address this question, we aim to examine the metabolic effects of early dinner, late dinner, and late dinner followed by delayed sleep, in healthy adults. Methods Dinner Time 2 Study is a randomized crossover trial with 3 treatment arms with a 3-4-week washout period: (1) early dinner + routine sleep; (2) late dinner + routine sleep; (3) late dinner + late sleep. Dinner times and bedtimes will be customized to each participant's central circadian rhythm (assessed by dim light melatonin onset, DLMO). The primary objectives of this study are to (1) examine the metabolic effects of early dinner (DLMO-3h) vs late dinner (DLMO+1h) with a fixed routine bedtime (DLMO+2h); (2) examine the metabolic effects of routine bedtime (DLMO+2h) vs delayed bedtime (DLMO+6h) with a fixed late dinner time (DLMO+1h). We will examine 24-h profiles of glucose, insulin, free fatty acids, triglycerides, and dietary fat oxidation using serial blood sampling and an ingested stable isotope ([2H31] palmitate) tracer. We aim to recruit 20 healthy adults, age 18-30 years old, with a BMI 18-29.9 kg/m2. Participants who perform night shift work or have any sleep disorders or metabolic diseases including diabetes are ineligible. Each participant will have 4 overnight admissions to our Clinical Research Unit (1 DLMO visit and 3 metabolic visits). A total of 3 participants have successfully completed the protocol since recruitment started in 2021. Conclusion Dinner Time 2 will greatly advance our understanding of the interactions between meal timing, sleep timing, and metabolism, which could inform the design and implementation of future studies that leverage chronobiology to combat diabetes and obesity. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Editorial introductions.

Editorial introductions.

The Effect of Nitazoxanide on the Clinical Outcomes in Patients with COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Nitazoxanide, a US Food and Drug Administration-approved antiparasitic agent, was reported to be effective in treating coronavirus disease 2019 (COVID-19). The lack of effective and precise treatments for COVID-19 infection earlier in the pandemic forced us to depend on symptomatic, empirical, and supportive therapy, which overburdened intensive care units and exhausted hospital resources. Therefore, the aim of this systematic review and meta-analysiswas to assess the efficacy and safety of nitazoxanide for COVID-19 treatment. A systematic review and meta-analysis synthesizing relevant randomized controlled trials from six databases (MedRxiv, WOS, SCOPUS, EMBASE, PubMed, and CENTRAL) until 17 May 2022was conducted. Risk ratio (RR) for dichotomous outcomes was usedand data with a 95% confidence interval (CI)arepresented. The protocol was registeredin PROSPERO with ID: CRD42022334658. Six randomized controlled trials with 1412 patientswere included in the analysis. Nitazoxanide was effective in accelerating viral clearance compared with placebo (RR: 1.30 with 95% CI 1.08, 1.56, p = 0.006) and reducing oxygen requirements (RR: 0.48 with 95% CI 0.39, 0.59, p = 0.00001), but we found no difference between nitazoxanide and placebo in improving clinical resolution (RR: 1.01 with 95% CI 0.94, 1.08, p = 0.88), reducing the mortality rate (RR: 0.88 with 95% CI 0.4, 1.91, p = 0.74), and intensive care unit admission (RR: 0.69 with 95% CI 0.43, 1.13, p = 0.14). Moreover, nitazoxanide was as safe as placebo (RR: 0.9 with 95% CI 0.72, 1.12, p = 0.34). Compared with placebo, nitazoxanide was effective in expediting viral clearance and decreasing oxygen requirements. However, there was no difference between nitazoxanide and placebo regarding clinical response, all-cause mortality, and intensive care unit admission. Therefore, more large-scale studies are still needed to ascertain the clinical applicability of nitazoxanide in COVID-19.

The Implementation of a Geriatrics Co-Management Model of Care Reduces Hospital Length of Stay.

(1) Background: Older adults comprise a large proportion of hospitalized patients. Many are frail and require complex care. Geriatrics has developed models of care specific to this inpatient population. Our objective was to demonstrate the effect of a geriatric co-management team on clinical administrative indicators of care in Clinical Teaching Units (CTUs) that have adopted the Age-friendly Hospital (AFH) principles in Brazilian hospitals. (2) Methods: Following 3 months of implementation of the AFH principles in CTUs, two periods of the same 6 months of two consecutive years were compared. (3) Results: The total number of participants in the study was 641 and 743 in 2015 and 2016, respectively. Average length of patient-stay (length of stay: 8.7 ± 2.7 vs. 5.4 ± 1.7 days) and number of monthly complaints (44.2 ± 6.5 vs. 13.5 ± 2.2) were significantly lower with the co-management model. Number of homecare service referrals/month was also significantly higher (2.5 ± 1 vs. 38.3 ± 6.3). The 30-day readmission rates and total hospital costs per patient remained unchanged. (4) Conclusion: The presence of a geriatric co-management team in CTUs is of added benefit to increase the efficiency of the AFH for vulnerable older inpatients with reduced LOS and increased referrals to homecare services without increasing hospital costs.

The economic burden of malaria inpatients and its determinants during China's elimination stage.

Malaria burden is still worrisome, while empirical evidence from malaria-eliminated countries including China may provide inspiration for the world. This study aimed to investigate China's malaria hospitalization costs and explore its determinants. Stratified multistage sampling across provincial, municipal, and county hospitals was conducted in 2017. All the malaria medical records were retrieved from 2014 to 2016 in 70 hospitals. Parametric and non-parametric methods were employed to estimate hospitalization costs, and the non-parametric bootstrap was used to compare hospitalization costs among sample areas and assessed the uncertainty of its differences. Quantile regressions were conducted to identify the determinants of hospitalization costs. The median hospitalization costs of 1633 malaria inpatients were 628 USD. Medication and laboratory tests accounted for over 70% of total expenditure. The median reimbursement rate was 41.87%, and this number was even lower in higher-level hospitals (<35%) and among the New Rural Cooperative Medical Scheme (<40%). Finally, health insurance type, hospital tier, clinical units, unknown fever, and comorbidity were the main determinants of hospitalization costs. The disparity of health protection for malaria hospitalization between rural and urban areas was noteworthy. Equivocal diagnosis and comorbidity are contributors of high cost as well. A reasonable payment system and enhanced capacities to treat malaria in a cost-effective way are suggested to reassure malaria economic burden.

Creation of a Clinical Demonstration Unit: Embedding Academic Research into Point of Care in a Geriatric Unit.

Given that there are limited evidence-informed non-pharmacological interventions to treat behavioural and psychological symptoms of dementia, a specialized psychiatric hospital partnered with an academic university to create a clinical demonstration unit (CDU) - a learning health systems (LHS) model to advance dementia care. In this paper, we identify five key enablers that led to the successful creation of the CDU, its achievements and challenges encountered. The paper provides learnings for other healthcare providers who are considering initiating an LHS model within their setting to advance patient care.

Dosimetric Evaluation of Physical Radiation Delivery Limits of a Weak Magnetic Field Generator on GBM Dose Distributions

<h3>Purpose/Objective(s)</h3> To demonstrate the feasibility of meeting dose prescription criteria when using a weak magnetic field generator to support glioblastoma multiforme (GBM) radiation therapy. <h3>Materials/Methods</h3> Weak magnetic fields extend free radical life, and recent experimental results have shown that adding weak magnetic fields (20G-40G) to radiation therapy delivery enhances free radical production, increases tumor cell death, and slows tumor growth. Based on these results, we have built the first clinical unit, consisting of two 63 cm ID Helmholtz coils, spaced 35 cm apart. The coil system is placed such that the patient and Linac couch are within the coils, and the Linac isocenter is coincident with the center of the coil system. We propose to use GBM for our first clinical trial. The limitation imposed by the coil system is a fixed Linac couch angle, constraining the gantry rotation to slightly more than 180°, from lateral to lateral. The impact on treatment plan quality of the corresponding reduction in available beam angles was unknown, so we conducted a treatment planning study to determine if we could provide clinically equivalent treatment plans with the coil in place. We evaluated the treatment plans for 10 GBM patients that had been treated with arc therapy. The prescription was 60 Gy (2 Gy x 30 fractions) for 6 patients, 55.8 Gy (1.8 Gy x 31 fractions) for 2 patients, 54 Gy (1.8 Gy x 30 fractions) for 1 patient, and 40.05 Gy (2.67 Gy x 15 fractions) for 1 patient. The dose was delivered to 95% of the planning target volume (PTV). The PTV margin was 1.3-2 cm surrounding the gross tumor volume. Critical structures, such as the brainstem, optic nerves, and optic chiasm, were contoured and assigned constraints of 62 Gy, 54 Gy, and 54 Gy, respectively. We repeated the treatment planning session using only coplanar arcs that spanned from 90° to 270° (half-arcs). <h3>Results</h3> All the treatment plans generated with the half-arcs met the clinical criteria. The minimum PTV doses for the half arc and clinical plans were 50.0 ± 6.1 Gy and 51.4 ± 7.1 Gy, and the maximum PTV doses were 61.9 ± 7.1 Gy and 62.7 ± 8.6 Gy, respectively. Table 1 summarizes the results of four reported critical structures. All the critical structures met the criteria, and the half-arc plans were neither better nor worse than the clinical plans. <h3>Conclusion</h3> The physical limits imposed by the magnetic field generator on the Linac beam angles do not degrade treatment planning for GBM radiation therapy. The prescribed dose can be adequately delivered while avoiding critical structures. With this groundwork, we can develop clinical trials to evaluate the impact of utilizing weak magnetic fields in radiation therapy.

Preventing Patient Falls Overnight Using Video Monitoring: A Clinical Evaluation.

Inpatient falls are devastating for patients and their families and an ongoing problem for healthcare providers worldwide. Inpatient falls overnight are particularly difficult to predict and prevent. The aim of this cohort study was to evaluate effectiveness of overnight portable video monitoring as an adjunct falls prevention strategy for high falls risk patients in inpatient clinical units. Over three months, three clinical inpatient wards were provided with baby monitor equipment to facilitate portable video monitoring. Portable video monitoring registers were completed nightly and nursing staff were invited to complete surveys (n = 31) to assess their experiences of using portable video monitoring. A total of 494 episodes of portable video monitoring were recorded over the three-month period, with clinical areas reporting a total of four inpatient falls from monitoring participants (0.8% of total portable video monitoring episodes). Overall, there was a statistically significant reduction in total inpatient falls overnight on the target wards. Surveyed nursing staff reported feeling better equipped to prevent falls and indicated they would like to continue using portable monitoring as a falls prevention strategy. This study provides evidence to support the use of portable video monitoring as an effective falls prevention strategy in the hospital environment.

WILL (When to Induce Labour to Limit risk in pregnancy hypertension): a multicentre randomised controlled trial — adaptations to deliver a timing-of-birth trial during the COVID-19 international pandemic

BackgroundAs a pragmatic randomised timing-of-birth trial, WILL adapted its trial procedures in response to the COVID-19 pandemic. These are reviewed here to inform post-pandemic trial methodology.MethodsThe trial (internal pilot) paused in March 2020, re-opened in July 2020, and is currently recruiting in 37 UK NHS consultant-led maternity units. We evaluated pandemic adaptations made to WILL processes and surveyed sites for their views of these changes (20 sites, videoconference).ResultsDespite 88% of sites favouring an electronic investigator site file (ISF), information technology requirements and clinical trial unit (CTU) operating procedures mandated the ongoing use of paper ISFs; site start-up delays resulted from restricted access to the CTU. Site initiation visits (SIVs) were conducted remotely; 50% of sites preferred remote SIVs and 44% felt that it was trial-dependent, while few preferred SIVs in-person as standard procedure. The Central team felt remote SIVs provided scheduling and attendance flexibility (for sites and trial staff), the option of recording discussions for missing or future staff, improved efficiency by having multiple sites attend, and time and cost savings; the negative impact on rapport-building and interaction was partially mitigated over time with more familiarity with technology and new ways-of-working. Two methods of remote consent were developed and used by 30/37 sites and for 54/156 recruits. Most (86%) sites using remote consenting felt it improved recruitment. For remote data monitoring (5 sites), advantages were primarily for the monitor (e.g. flexibility, no time constraints, reduced cost), and disadvantages primarily for the sites (e.g. document and access preparation, attendance at a follow-up meeting), but 81% of sites desired having the option of remote monitoring post-pandemic.ConclusionsCOVID adaptations to WILL trial processes improved the flexibility of trial delivery, for Central and site staff, and participants. Flexibility to use these strategies should be retained post-pandemic.Trial registrationISRCTN77258279. Registered on 05 December 2018.

Moral distress to moral success: Strategies to decrease moral distress.

Moral distress, which is especially high in critical care nurses, has significant negative implications for nurses, patients, organizations, and healthcare as a whole. A moral distress workshop and follow-up activities were implemented in an intensive care unit in order to decrease levels of moral distress and increase nurses' perceived comfort and confidence in ethical decision-making. A quality improvement (QI) initiative was conducted using a pre- and post-intervention design. The program consisted of a four-hour interactive workshop, followed by two individual self-reflection activities at 2-3weeks and 5-6weeks after the workshop. Critical care nurses working in a heart and vascular intensive care unit at a large academic medical center. This study was deemed to be a QI project by the institution's Institutional Review Board. Participation was voluntary. Nurses experienced a significant decrease in moral distress. The participants' average ethical confidence increased in four areas (ability to identify the conflicting values at stake, knowing role expectations, feeling prepared to resolved ethical conflict, and being able to do the right thing), with knowledge of role expectations and feeling prepared to resolve ethical conflict yielding statistically significant increases. Qualitative findings resulted in consistent themes related to causes of moral distress and ways nurses approached addressing moral distress. This study reinforces previous evidence on moral distress and its causes in critical care nurses, and provides a mechanism for improving moral distress and ethical confidence. This QI study demonstrates the effectiveness of an evidence-based program for decreasing critical care nurses' moral distress and increasing their ethical confidence. The strategies described in this paper can replicated by nursing leaders who wish to effect change at their local level, or adapted and expanded to other professions and clinical care units.

Effect of COVID-19 Pandemic on Hematopoietic Stem Cell Transplant Activity: Experience of a JACIE-Accredited Center.

The adoption of international quality and accreditation standards is important for the success of transplant centers. Guidelines from the Joint Accreditation Committee ISCT-Europe and EBMT (JACIE) have enabled quality management of the operations of clinical units of cellular therapy centers, including cell collection and processing, thus minimizing errors and adverse events. COVID-19 has had significant implications for immunocompromised patients, particularly hematopoietic stem cell transplant recipients, as well as their donors and caregivers. Here, we retrospectively examined measures, taken in our transplant center in Turkey during the pandemic period between March 2020 and October 2021, to investigate how JACIE accreditation has affected patient, donor, product, and employee safety. We analyzed data on transplant activity, as well as donor, patient, product, and employee safety, during the pandemic in 3 separate 6- month periods. The measures were analyzed starting from March 2020, when the first COVID-19 case was seen in Turkey. Since the beginning of the pandemic, 140 patients have undergone stem cell transplant in our center. Stem cell transplant was delayed in 22 patients because of the pandemic. Transplant was also postponed due to COVID-19 positivity in 6 patients, and 2 patients died due to COVID-19 infection during the transplant process. Unrelated donor activity continued to be performed safely throughout this period. COVID- 19 infection developed in 12 of the 52 personnel working in the bone marrow transplant unit, one of whom needed intensive care due to severe pneumonia. In terms of quality management activities, the impact of the pandemic was greatest during the first month. Results from our retrospective study examining the impact of JACIE accreditation in a stem cell transplant center during the COVID-19 pandemic showed that, when national and international guidelines are followed, JACIE accreditation can facilitate adaptation to changing conditions in transplant centers.

Differences in the choroid plexus volume and microstructure are associated with body adiposity.

The choroid plexus (CP) is a cerebral structure located in the ventricles that functions in producing most of the brain’s cerebrospinal fluid (CSF) and transporting proteins and immune cells. Alterations in CP structure and function has been implicated in several pathologies including aging, multiple sclerosis, Alzheimer’s disease, and stroke. However, identification of changes in the CP remains poorly characterized in obesity, one of the main risk factors of neurodegeneration, including in the absence of frank central nervous system alterations. Our goal here was to characterize the association between obesity, measured by the body mass index (BMI) or waist circumference (WC) metrics, and CP microstructure and volume, assessed using advanced magnetic resonance imaging (MRI) methodology. This cross-sectional study was performed in the clinical unit of the National Institute on Aging and included a participant population of 123 cognitively unimpaired individuals spanning the age range of 22 – 94 years. Automated segmentation methods from FreeSurfer were used to identify the CP structure. Our analysis included volumetric measurements, quantitative relaxometry measures (T 1 and T 2), and the diffusion tensor imaging (DTI) measure of mean diffusivity (MD). Strong positive associations were observed between WC and all MRI metrics, as well as CP volume. When comparing groups based on the established cutoff point by the National Institutes of Health for WC, a modest difference in MD and a significant difference in T 1 values were observed between obese and lean individuals. We also found differences in T1 and MD between obese and overweight individuals as defined using the BMI cutoff. We conjecture that these observations in CP volume and microstructure are due to obesity-induced inflammation, diet, or, very likely, dysregulations in leptin binding and transport. These findings demonstrate that obesity is strongly associated with a decline in CP microstructural integrity. We expect that this work will lay the foundation for further investigations on obesity-induced alterations in CP structure and function.

Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia

Opioids can cause severe respiratory depression by suppressing feedback mechanisms that increase ventilation in response to hypercapnia. Following the addition of boxed warnings to benzodiazepine and opioid products about increased respiratory depression risk with simultaneous use, the US Food and Drug Administration evaluated whether other drugs that might be used in place of benzodiazepines may cause similar effects. To study whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia. Randomized, double-blind, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) with 25 healthy participants from January 2021 through May 25, 2021. Oxycodone 10 mg on days 1 and 5 and the following in a randomized order for 5 days: paroxetine 40 mg daily, quetiapine twice daily (increasing daily doses from 100 mg to 400 mg), or placebo. Ventilation at end-tidal carbon dioxide of 55 mm Hg (hypercapnic ventilation) using rebreathing methodology assessed for paroxetine or quetiapine with oxycodone, compared with placebo and oxycodone, on days 1 and 5 (primary) and for paroxetine or quetiapine alone compared with placebo on day 4 (secondary). Among 25 participants (median age, 35 years [IQR, 30-40 years]; 11 female [44%]), 19 (76%) completed the trial. The mean hypercapnic ventilation was significantly decreased with paroxetine plus oxycodone vs placebo plus oxycodone on day 1 (29.2 vs 34.1 L/min; mean difference [MD], -4.9 L/min [1-sided 97.5% CI, -∞ to -0.6]; P = .01) and day 5 (25.1 vs 35.3 L/min; MD, -10.2 L/min [1-sided 97.5% CI, -∞ to -6.3]; P < .001) but was not significantly decreased with quetiapine plus oxycodone vs placebo plus oxycodone on day 1 (33.0 vs 34.1 L/min; MD, -1.2 L/min [1-sided 97.5% CI, -∞ to 2.8]; P = .28) or on day 5 (34.7 vs 35.3 L/min; MD, -0.6 L/min [1-sided 97.5% CI, -∞ to 3.2]; P = .37). As a secondary outcome, mean hypercapnic ventilation was significantly decreased on day 4 with paroxetine alone vs placebo (32.4 vs 41.7 L/min; MD, -9.3 L/min [1-sided 97.5% CI, -∞ to -3.9]; P < .001), but not with quetiapine alone vs placebo (42.8 vs 41.7 L/min; MD, 1.1 L/min [1-sided 97.5% CI, -∞ to 6.4]; P = .67). No drug-related serious adverse events were reported. In this preliminary study involving healthy participants, paroxetine combined with oxycodone, compared with oxycodone alone, significantly decreased the ventilatory response to hypercapnia on days 1 and 5, whereas quetiapine combined with oxycodone did not cause such an effect. Additional investigation is needed to characterize the effects after longer-term treatment and to determine the clinical relevance of these findings. ClinicalTrials.gov Identifier: NCT04310579.

Evaluating smoking cessation service at an emergency department clinical observation unit.

To evaluate the effectiveness of a pilot smoking cessation service in an emergency department (ED) clinical observation unit. A descriptive case series review was undertaken of smoking cessation service patients in the short-stay unit of an acute hospital in Singapore from July 1, 2018, to December 31, 2019. Upon admission, ED nurses screen all patients regarding their current smoking status and implement the 5 A's framework, which involves the steps of Ask-Advise-Assess-Assist-Arrange. Patients in the "contemplation" and "preparation" stages were offered the following components: (1) a bedside counseling session by a pharmacist and (2) a follow-up appointment at an outpatient smoking cessation clinic. Postdischarge follow-up telephone calls at 1, 6, and 12 months were carried out as part of the study data collection to obtain abstinence information. Forty-seven patients were included in the study; the majority were male (n = 41; 87.2%). The median numbers of cigarettes smoked per day at baseline, 1 month, 6 months, and 12 months were 14, 5, 3, and 5, respectively. The overall point-prevalence abstinence rates over the same follow-up time points were 26.5%, 38.7%, and 31.3%, respectively. The proportions of patients lost to follow-up at 1 month, 6 months, and 12 months were 27.7%, 34.0%, and 31.9%, respectively. Given the small sample and high number of uncontactable patients, more research is needed to assess whether the trend toward increasing point-prevalence abstinence rate over time and the trend toward decreasing median number of cigarettes smoked are observed in a larger sample.

Improving feedback students receive on documentation during the obstetrics and gynecology clerkship

BACKGROUNDStudents need feedback on written documentation to optimize their long-term development of this important clinical skill. The culture in surgical specialties does not always prioritize feedback regarding this skill.OBJECTIVEThis study aimed to examine the effectiveness of 2 specific forms to improve the quantity and quality of feedback to students about their medical documentation.STUDY DESIGNIn a multiphase quality improvement project, medical students were surveyed after the obstetrics and gynecology clerkship regarding their experience of receiving feedback on written notes. The proportions of students who received feedback on notes and those rating the feedback as meaningful were measured before and after the implementation of a required, formative feedback card. In phase 2, students were randomized to use a simplified feedback card or the original detailed card, and outcomes were compared. This study was conducted at the Medical University of South Carolina, a tertiary care academic medical center. The participants included third-year medical students that completed their 6-week obstetrics and gynecology clerkship.RESULTSBefore the intervention, of 82 students, 70 (85%) and 55 (67%) received feedback on written notes in the inpatient and outpatient settings, respectively, which increased to 99.6% (254/255) and 98.5% (251/255) (P<.001) after the implementation of any feedback card. Moreover, the proportion of students who felt the feedback helped them improve their clinical documentation skills increased from 72% to 90% (P<.001) with the use of a feedback card. These improvements were noted in all clinical units within the clerkship. There was no difference (P=.3) in outcomes between the simplified and detailed cards.CONCLUSIONA formative card is a simple, cost-effective, low-resource intervention that can increase both the quantity and quality of written note feedback that students receive during their obstetrics and gynecology clerkship. A less detailed card achieved comparable outcomes and increased faculty satisfaction.

Effects of intravenous lysine acetylsalicylate versus oral aspirin on platelet responsiveness in patients with ST-segment elevation myocardial infarction

Abstract Background Prasugrel and ticagrelor, new P2Y12-ADP receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events in patients with an acute coronary syndrome. However, evidence is lacked about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared to oral aspirin on prasugrel inhibited platelets in patients with an ST-segment elevation myocardial infarction (STEMI). Methods This is a prospective, randomized, multicenter, open platelet function study conducted. STEMI patients were randomly assigned to receive a loading dose (LD) of intravenous LA 450mg plus oral ticagrelor 180mg, or LD of aspirin 300mg plus ticagrelor 180mg orally. Platelet function was evaluated at baseline, 30 min, 1h, and 24h using multiple electrode aggregometry and vasodilator-stimulated phosphoprotein phosphorylation (VASP). The primary endpoint of the study is the inhibition of platelet aggregation after arachidonic acid (AA) 1.5mM at 30 min. Secondary endopoints are the inhibition of platelet aggregation after AA baseline and at 1h, and 24h, and measurement of aggregation with other platelet test (ADP, collagen and VASP). Results A total of 32 STEMI patients were randomized (16 LA, 16 aspirin). The inhibition of platelet aggregation after AA 1.5 mM at 30 min was greater in subjects treated with LA compared with aspirin: 166 vs. 412 respectively, p=0.001. This differential effect was observed at 1 hour (p=0.01), but not at 24 hours. Subjects treated with LA presented less variability and faster and greater inhibition of platelet aggregation with AA compared with aspirin (Figure 1). Conclusions The administration of intravenous LA resulted in a significantly reduction of platelet reactivity compared to oral aspirin on ticagrelor inhibited platelets in patients with STEMI. Loading dose of LA achieves an earlier platelet inhibition, and with less variability than aspirin. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the CTU-SCReN (Clinical Trial Unit – Spanish Clinical Research Network) from San Carlos University Hospital (Madrid, Spain), financed by the ISCII (Project PI16/00191)

How to relate progestogen-only pill guidance to clinical practice

A new guideline for the use of progestogen-only pills has been published. Claire Nicol explains how this relates to clinical practice The Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Healthcare (FSRH) regularly updates and develops national UK clinical guidelines relating to contraception. The updated FSRH progestogen-only pills (POPs) guideline was published in August 2022 and gives an overview of all POPs available in the UK. This article will highlight what is new or important in the guideline and how to relate the recommendations to clinical practice.

An Overview of Candidemia Patients in Tertiary Hospital, Surabaya, Indonesia

Candidaemia is a bloodstream infection (BSIs) caused by Candida spp. common in hospitalized patients. Candidemia has a high mortality and morbidity. This study aimed to give an idea about incidence, patient characteristics, species and patterns of candida susceptibility, and risk factors in candidaemia patients at Dr. Soetomo Hospital from January to December 2020. This is descriptive research using an observational research design. This study used a medical record instrument for candidemia patients in the inpatient ward of Dr. Soetomo and data in the form of records of blood culture results at the Clinical Microbiology Unit of RSUD Dr. Soetomo Surabaya for the period January-December 2020. The observed variables include incidence, sex, age, the origin of hospitalization, species distribution, frequency of antifungal sensitivity testing, and risk factors for candidemia. In 12 months, 53 candidemia patients were treated at Dr. Soetomo Hospital. The incidence of candidemia is 1.58 cases per 1000 person-years. Most of them are male (64.15%) and aged less than <1 year (28,30). Most of the medical units at the time of the diagnosis were intensive care units and pediatric wards (28.30%). Candida albicans was the most commonly found species (33.96%), then Candida tropicalis (26.41%) and Candida parapsilosis (24.53%). Two Candida glabrata isolates (40%) were susceptible to caspofungin, and all isolates (100%) of Candida albicans, Candida parapsilosis, Candida rugosa, Candida lusitaniae, Candida tropicalis, Candida dubliniensis, and were susceptible to the antifungals tested. Patients who use the Central Venous Catheter (CVC) have the highest level of risk factor, followed by patients with diabetes mellitus.

Exploring the construction of clinical trial research unionsin China

<p indent="0mm">A clinical trial is a key step in the process of pharmaceutical research and development (R &amp; D). It is a key indicator of the innovative potential of the pharmaceutical industry. ClinicalTrials.gov shows that the average annual growth rate of the total number of clinical trials globally in the past decade (2012–2021) was 20.7%, mainly distributed in Europe and the United States, and the total number of clinical trials registered in China accounted for 6% of the world. According to the statistics of IQVIA Institute for Human Data Science, the global proportion of early-stage R &amp; D pipelines from China-headquartered companies increased from 1% in 2005 to 12% in 2020, which was still far behind that of European and American companies. Among 871 new active substances approved for marketing globally in the past two decades, 522 were for marketing in China, with the high number driven by regulatory acceleration mechanisms from National Medical Products Administration, such as breakthrough and orphan designations and priority reviews. Considering the gap in clinical research strength between China and developed countries such as Europe and the United States, the clinical trial research capacity and level should be improved to assist China in the R &amp; D of innovative drugs. According to the Registration and Information Disclosure Platform for Drug Clinical Studies and the clinical trial institution filing management information platform in China, in the last five years (2017–2021), the average annual growth rates of the total number of new drug clinical trial registration and clinical trial units in China reached 26.9% and 12.6%, respectively. However, clinical trial resources are mainly concentrated in major institutions, municipalities, or provincial capital cities in the eastern and central regions of China, with distributions becoming increasingly polarised. Under the background of China’s new medical reforms, the strategic direction of national political support is to motivate equitable access to high-quality clinical trial resources and cross-regional collaborative development of medical institutions by means of medical unions, national clinical medical research centres, Chinese national major projects for new drug innovation and so on. In the context of this background, clinical trial research unions (CTRUs) have been built in China. A CTRU is defined as a consortium formed by medical institutions, sponsors and third-party service institutions of various levels and functions, led by a national clinical medical research centre or clinical trial medical institutions undertaking major national science and technology projects or supporting projects of national key R &amp; D plans, radiating and driving the improvement of clinical trial research capacity in multiple regions. CTRUs develop a multi-level clinical research centre system and collaborative network by vertically and horizontally combining multi-level medical institutions, sponsors and third-party service institutions. All participants of CTRUs are crucial. The leading clinical trial research medical institution, as the core, is responsible for establishing institutional system standards in CTRUs, designing and leading high-quality multi-centre clinical trials, central ethics and personality training. The major clinical trial research medical institutions are responsible for implementing high-quality, multi-centre, complex and high-risk clinical trials. The other member institutions are responsible for implementing basic clinical trials. The sponsors, contract research organizations (CROs), site management organizations (SMOs) and other enterprises are responsible for funding, supporting and promoting the construction of a clinical trial centre system and collaborative network. The specific construction contents of CTRUs include building a clinical trial research resource sharing platform, homogenising clinical trial quality management, constructing a rapid clinical trial process platform, diversified multi-level and multi-form talent training, information interconnection, deepening strategic cooperation and designing and leading high-level trials. CTRUs have established the selection criteria and assessment exit mechanism and conducted work performance assessments from the dimensions of organisation and implementation, division of labour and cooperation, the connection of clinical trial resources from top to bottom, efficiency and benefit and sustainable development to ensure their good and sustainable development. Through CTRUs, we can achieve high-quality clinical trial resource sharing, improve the clinical trial research capability of member institutions, cultivate high-level skills, such as principal investigators (PIs), sub-investigators, institutional managers and clinical research coordinators (CRCs), and promote the development of clinical trials, economically and with high-quality. Through the trial operation with one member of CTRUs, it was found that the key points should be strengthened in deepening resource sharing, implementing central ethics review, interconnecting information platforms and leading high-quality clinical trials. The construction of CTRUs is an effective means for China’s clinical trial research to solve the current problems and change from a ‘follow-on pattern’ to leading high-level and high-quality international multi-centre trials. However, the construction of CTRUs is a complex systematic project. In addition to performing an excellent job in the top-level design and overall planning, CTRUs’ specific implementation process and measures need to be continuously explored in the practice process.

An Assessment of Asymptomatic Bacteriuria During Pregnancy and Antimicrobial Resistance to its Common Bacterial Isolates in the Urine

Objective: The objective of this study is to assess asymptomatic bacteriuria during pregnancy and its antimicrobial resistance to the common bacterial isolates in the urine. Study Design and Setting: The cross-sectional study was carried out in the Antenatal Clinic, Obstetrics and Gynaecology Unit of Avicenna Medical and Dental Hospital, Lahore, Pakistan. Methodology: This descriptive, cross-sectional study lasted for nine months and information was collected with the help of a self-designed questionnaire using non-probability random sampling. The frequency distribution of socio-economic and demographic factors of 167 pregnant women was observed while the cultural examination was performed on urine samples of diagnosed cases of asymptomatic bacteriuria through microscopy to find out antimicrobial resistance against bacterial isolates. Results: The prevalence rate of asymptomatic bacteriuria was 13.2%. The most common pathogen was E. coli followed by Klebsiella Pneumoniae and Staphylococci. Resistance of urine pathogens was observed against Ampicillin, Amoxiclav, Norfloxacin, and Piperacillin/Tazobactam. Conclusion: E. coli was identified as the most predominant pathogen that showed higher resistance to Cefotaxime. History of renal stone, trimester, parity, education and low-socio-economic status were the significant factors for ASB