Protocol Violations Research Articles

Abstract TMP38: Remote Research Practices Enhance Acute Stroke Clinical Trial Enrollment

Background: Many acute stroke clinical trials (ASCTs) are underpowered, inconclusive, or terminated early. A pervasive challenge to ASCT recruitment is the physical separation of patients, their legally authorized representatives, research coordinators, and clinician investigators when trial-eligible patients present emergently. Remote research practices (RRPs) may aid time-critical ASCT enrollment and follow-up, however, their feasibility and effectiveness are understudied. Methods: We retrospectively reviewed ASCT enrollment (NCT03785678, NCT03735979, NCT02072681) at two institutions. Essential clinical trial elements (ECTEs) consisted of eligibility screening, informed consent, randomization, study intervention, and inpatient/outpatient follow-up assessments. When conventional in-person clinical research was not possible, ECTEs were attempted via RRPs utilizing either telemedicine evaluation or telephone communication. The primary outcome was the successful execution of accurate, complete ECTEs by research communication modality (in-person, telemedicine, or telephone). The secondary outcome was the protocol violation rate by modality. We utilized Fisher’s Exact Test for primary and secondary outcomes and descriptive statistics to report RRP utilization. Results: A total of 1600 individual ECTEs were attempted on 169 subjects. RRPs were utilized for 53.7% of ECTEs (19.1% telemedicine, 34.6% telephone). ECTEs were more likely to be completed successfully with telemedicine (100%) than in-person (98.5%) or telephone (92.2%), (p<0.01). Additionally, protocol deviations were less common with telemedicine (0.0%) than in-person (2.6%), or telephone (2.8) (p=0.04). Randomization (94.7%) and outpatient assessments (90.3%) were frequently completed via RRPs compared to eligibility screening (39.1%), informed consent (40.2%), supervision of study intervention (36.8%), and inpatient assessments (21.9%). Conclusion: RRPs were widely utilized. Telemedicine execution of ECTEs was associated with the highest rate of successful completion and lowest rate of protocol deviations. These findings, while retrospective and confounded by indication, suggest RRPs are effective and require confirmatory study.

The Appropriately Designed TDM Clinical Trial: Endpoints, Pitfalls, and Perspectives

Appropriately designed clinical trials can provide the evidence needed to broadly implement therapeutic drug monitoring (TDM). In the past 30 years, some stunning successes but also some fascinating failures in demonstrating the benefits of TDM have been observed. Future TDM studies can be designed based on this experience. The manuscript is based on a combination of personal experience and published articles and discusses several aspects of the design and conduct of TDM studies. Recommendations are provided to reduce the risk of protocol violations and to maximize the potential impact of a TDM study on clinical practice. There are lessons that can be learned from previous experience, and this article gives an overview of potential TDM study designs, endpoints, pitfalls, and perspectives.

P418 Dose escalation of oral 5-aminosalicylic acid for ulcerative colitis with Mayo endoscopic subscore of one improves long-term prognosis: a one-year multicentre, open-label, randomized controlled trial.

Abstract Background Endoscopic healing, one of the treatment targets for ulcerative colitis (UC), is commonly defined as Mayo endoscopic sub-score (MES) ≤1. Furthermore, patients in whom MES of 0 is achieved are at a lower risk of relapse than those with MES of 1. However, it is unclarified whether the therapeutic intervention of dose escalation of oral 5-aminosalicylic acid (5-ASA) improves the prognosis of UC patients in clinical remission with MES of 1. Methods A multicentre, open-label, randomized, controlled trial was conducted among 5 hospitals in Japan from March 2018 to June 2022. Patients with UC, aged 16 years or older, treated with 5-ASA, in clinical remission and confirmed MES of 1 were enrolled. Patients receiving maintenance therapy other than oral 5-ASA and thiopurine (e.g., topical therapy, biologics) were excluded. Patients were randomly assigned to either the therapeutic intervention group (increased the dose of 5-ASA) or the control group (without any intervention). Concomitant use of immunomodulator (IM) was used for the stratification factor in the randomization. The primary endpoint was clinical relapse within one year. Relapse was defined as both (1) pMayo ≥3 or rectal bleeding sub-score ≥1, and (2) addition of any induction treatments for UC including topical agents. Predictive factors for relapse and adverse events (AEs) were investigated as the secondary outcomes. The predictive factors were explored in the multivariable Cox regression analysis. Results Eighty-one patients were enrolled and randomly assigned into the therapeutic intervention or the control group, and two patients were excluded due to important protocol violations after the randomization. Finally, 79 patients (n=39; therapeutic intervention, n=40; control) were included in the full analysis set (FAS). In the FAS, 46 (58.2%) patients were male, and 20 (25.3%) patients were treated with IMs. The relapse within one year was less in the therapeutic intervention group (6/39; 15.4%) than the control group (15/40; 37.5%), significantly (P =0.026) (Fig.1). In the exploratory analysis for the predictors, concomitant use of IM was associated with relapse (hazard ratio, 2.52; 95% confidence interval, 1.04-6.12, P =0.041). There were three AEs in the therapeutic intervention group. Two patients complained of nausea, and the other complained of diarrhea and melena. All the AEs were improved after turning back the treatment to that before the intervention. Fig. 1. The proportion of patients relapsed within one year in the full analysis set (primary analysis). Conclusion The dose escalation of oral 5-ASA reduced the relapse within one year in UC patients in clinical remission with MES of 1.

Safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) during the month of Ramadan in patients with type 2 diabetes mellitus in Pakistani population-an observational study from a tertiary care center in Karachi.

Primary aim was to assess the safety of SGLT2-i in patients with Type 2 Diabetes Mellitus (T2D) in a real-life scenario during Ramadan by finding the frequency and severity of hypoglycemic/hyperglycemic events, dehydration, and Diabetic ketoacidosis (DKA). Secondary aim was to assess changes in glycated hemoglobin (HbA1c), weight and creatinine levels. This prospective, observational, controlled cohort study was conducted at Aga Khan University Hospital, Karachi, Pakistan from March 15 to June 30, 2021. Participants were over 21 years of age, on stable doses of SGLT2-I, which was started at least 2 months before Ramadan. Endpoint assessments were done 1 month before and within 6 weeks after Ramadan. Of 102 participants enrolled, 82 completed the study. Most (52%) were males, with mean age 52.2 ± 9.5 years and average duration of T2D 11.2 ± 6.5 years. 63% were on Empagliflozin (mean dose; 14.8 ± 7.2 mg/day) whereas 37% were on Dapagliflozin (mean dose; 8.2 ± 2.7 mg/day). Six (7.3%) documented symptoms of hypoglycemia. However, no episode of severe hypoglycemia, hyperglycemia, dehydration, DKA, hospitalization or discontinuation of SGLT2i was reported. HbA1c changes were (7.7 ± 1.2% from 7.9 ± 2.3%, p 0.34), weight (78.4 ± 12.9 kgs from 78.9 ± 13.3, p 0.23) and eGFR (87.8 ± 27.9 from 94.3 ± 37.6, p < 0.001). The reasons of study participants drop outs were: six did not keep any fasts; four discontinued study participation for personal reasons; three were out of city and missed post Ramadan follow-up, two protocol violation and five could not be contacted for post-Ramadan follow up during the third wave of COVID-19. Results showed the safety of SGLT2i agents during Ramadan in the Pakistani population recommending it as a treatment option in adults with T2D, without any additional adverse events.

Introducing the fragility index-A case study using the Term Breech Trial.

The fragility index (FI) is a sensitivity analysis of the statistically significant result of a clinical study. It is the number of hypothetical changes in the primary event of one of the two cohorts in a 1-to-1 comparative trial to render the statistically significant result non-significant (ie, to alter the P-value from ≤0.05 to >0.05). The FI can be compared with the patient drop-out rates and protocol violations, which, if much higher than the FI, may arguably suggest less robustness/stability of the trial's results. To illustrate the concept, we have chosen the Term Breech Trial (TBT) as a case study. The TBT results favor planned cesarean birth, as opposed to planned vaginal delivery, in the term singleton fetus with breech presentation. Our analysis shows that the FI of the TBT is 21, which is small in comparison to the number (hundreds) of protocol violations present. Some experts have suggested the inclusion of the FI in data analysis and subsequent discussion of clinical trial data. Routine use of such a metric may be valuable in encouraging readers to maintain a healthy degree of skepticism, especially when interpreting trial results which may directly influence clinical practice.

The Understanding of Large-Scale Social Restriction Policy towards Forms of Social Citizenship within the Jagakarsa Village Community

Jakarta is the area with the highest number of health protocol violators on the island of Java. Social citizenship emphasizes rights and obligations and requires awareness tools, social responsibilities to be articulated and represented among them through participation. The problem in this study is formulated with these questions: 1) Is there any influence of the understanding of the Large-Scale Social Restriction Policy (PSBB) on the forms of social citizenship within the Jagakarsa Village community? 2) What is the form of social citizenship of the Jagakarsa Village community during the implementation of the Large-Scale Social Restriction Policy (PSBB)? Here is the hypothesis, H0: There is no effect of understanding the policy of Large-Scale Social Restrictions on social citizenship. H1: There is an effect of understanding the policy of Large-Scale Social Restrictions on social citizenship. This research uses a mixed-method that combines quantitative and qualitative methods with an explanatory sequential strategy. Respondents and resource persons in this study are the people of Jagakarsa village. This study concludes that understanding the policy of Large-Scale Social Restrictions has an effect or gives positive results on the social citizenship variables. The Jagakarsa village community is categorized into the passive citizenship type.

Unreported protocol deviations - The tip of the research-berg.

Failure to stay within an ethics committee (EC)-approved protocol limits is termed protocol deviation or violation (PD/PV), depending on the seriousness of the transgression and its attendant risks and/or harms. PD/PVs arise in the post-approval phase of the research and are often missed. Current guidelines expect ECs to detect, report and recommend suitable actions such that research participants' risks and harms are mitigated, to the extent possible. Yenepoya Ethics Committee-1 conducted an internal audit of ongoing postgraduate dissertations involving human participants to assess the occurrence of PD/PVs. 54 out of 80 postgraduates responded to our request for filling out a self-reported checklist. These responses were followed up with physical verification of the protocol-related documents. Protocol transgressions were classified as non-compliance (administrative issues), protocol deviations (minor transgressions with minimal or less than minimal increase in attendant risk to participants) and protocol violations (serious transgressions with more than minimal increase in attendant risk to participants). The non-compliances included non-reporting for audit and non-reporting of PDs. Protocol deviations included non-conformance to EC validity, sample size, approved methodology, informed consent process and documentation and suboptimal data storage. No protocol violations were observed. We report PD/PVs from these 54 protocols - with our assessment on the negative impact it may have on scientific validity, harm to participants, EC functioning and credibility of the institution - in the hope that our readers appreciate this important aspect of the post-approval process in the functioning of an EC.

Experience of the Muslim Community Resistance During COVID-19 in Moluccas, Indonesia

The empirical analysis of this article presents an interpretation of religious attitudes expressed during the COVID-19 pandemic in the Muslim communities in Moluccas, Indonesia. The article explains religious experiences and the meanings of their resistance to COVID-19. Various measures to respond to the pandemic have created resistance in religious communities globally. As a result, there have been violations of health protocols, including in Indonesia. Data were obtained through interviews and observations around Ambon City, Moluccas, Indonesia. The data were analyzed through qualitative methods and constructivist paradigms based on a phenomenological perspective, especially a social constructionist perspective. This article explains the role that phenomenological and religious studies of resistance can play in understanding effective public health management and improving the government’s policies and the pandemic health protocols. Subjective experiences occurred in religious worship, community homes, educational institutions, and rituals amid uncertain information and political polarization. The results indicate that resistance encompasses planning, fraud, global disasters, negative labeling, panic, anxiety, and fear. Resistance will have an impact and become necessary due to the involvement of individuals; this affects daily life for religious belief and coping with fear, panic, and uncertainty of COVID-19. This article will benefit Muslim communities’ subjective experiences regarding resistance during the COVID-19 pandemic and encourage further research.

The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial

In animal studies, β-nicotinamide mononucleotide (NMN) supplementation increases nicotinamide adenine dinucleotide (NAD) concentrations and improves healthspan and lifespan with great safety. However, it is unclear if these effects can be transferred to humans. This randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial included 80 middle-aged healthy adults being randomized for a 60-day clinical trial with once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN. The primary objective was to evaluate blood NAD concentration with dose-dependent regimens. The secondary objectives were to assess the safety and tolerability of NMN supplementation, next to the evaluation of clinical efficacy by measuring physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective general health assessment [36-Item Short Form Survey Instrument (SF-36)]. Statistical analysis was performed using the Per Protocol analysis with significant level set at p = 0.05. All 80 participants completed the trial without trial protocol violation. Blood NAD concentrations were statistically significantly increased among all NMN-treated groups at day 30 and day 60 when compared to both placebo and baseline (all p ≤ 0.001). Blood NAD concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues, based on monitoring adverse events (AEs), laboratory and clinical measures, were found, and NMN supplementation was well tolerated. Walking distance increase during the six-minute walking test was statistically significantly higher in the 300 mg, 600 mg, and 900 mg groups compared to placebo at both days 30 and 60 (all p < 0.01), with longest walking distances measured in the 600 mg and 900 mg groups. The blood biological age increased significantly in the placebo group and stayed unchanged in all NMN-treated groups at day 60, which resulted in a significant difference between the treated groups and placebo (all p < 0.05). The HOMA-IR showed no statistically significant differences for all NMN-treated groups as compared to placebo at day 60. The change of SF-36 scores at day 30 and day 60 indicated statistically significantly better health of all three treated groups when compared to the placebo group (p < 0.05), except for the SF-36 score change in the 300 mg group at day 30. NMN supplementation increases blood NAD concentrations and is safe and well tolerated with oral dosing up to 900 mg NMN daily. Clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake. This trial was registered with ClinicalTrials.gov, NCT04823260, and Clinical Trial Registry - India, CTRI/2021/03/032421.

TINJAUAN YURIDIS PENEGAKAN HUKUM PIDANA KEKARANTINAAN KESEHATAN DALAM PENANGGULANGAN WABAH COVID-19 DI KOTA MEDAN

Law enforcement aims to improve order and legal certainty in society. As a form of efforts to achieve a comprehensive rule of law in law enforcement, especially when a certain virus outbreak or pandemic occurs, the Government together with the House of Representatives of the Republic of Indonesia. The role of the government and the community in the successful implementation of the Emergency Community Activity Restriction (PPKM) is in line with how the role is in the fulfillment of rights and obligations. The research method in this study is a normative legal approach. The main object is the norms or rules of positive legal rules that regulate criminal law policies as an effort to overcome the Covid-19 emergency. The criminal law enforcement process against perpetrators of health protocol violations in the city of Medan is in accordance with Law Number 6 of 2018 concerning Health Quarantine, however the government has not fully fulfilled the rights of the community during the implementation of large-scale social restrictions (PSBB) and the implementation of restrictions on community activities (PPKM). ). The role of the people of Medan City in dealing with Covid-19 and compliance with PPKM is still considered low. Based on data from the Medan City Government, the number of violations of the Covid-19 health protocol in Medan City is increasing. The latest data, from July 15 to August 09, 2021, as many as 52 people who violated health protocols (prokes) during Emergency PPKM and Level 4 PPKM in Medan City. The 52 people are non-essential, namely business actors and traders and have undergone a trial for minor crimes.

Government Policy Implementation Regarding Covid-19 in Makassar

This article discusses the policies of the targeted city local government related to Covid-19 regulations as well as policies issued by the government down to the regional level. The aim is simply to provide an overview of the situation in the areas affected by the disaster after the existence of local legal policies issued by the government in the research location. The research method used in this article is normative legal research. The results of this study describe the implementation of policies in efforts to deal with Covid-19 in Government regulations at the regional level, especially Makassar City which aims to prevent transmission of Covid-19. The implementation of local government regulations has made people aware of the importance of wearing masks, one of which is contained in the contents of the health protocol rules. The existence of policies issued by regulations is not yet an antidote to the Covid-19 virus, but this policy only prevents the spawning of Covid-19. The Covid-19 Task Force is tasked with assisting control and law enforcement against health protocol violations. The team was formed to carry out direct handling in the field in controlling and enforcing health protocol laws, especially in the Makassar City area. In order to reduce the transmission of the spread of the Covid-19 virus, the government should have policies that support each other so that it is more stringent in security and supervision during the implementation of the PSBB and it is hoped that it will patrol places more often that invite people to crowded places.

Implementation of Administrative Sanctions Against Violations Health Protocol Covid-19 in Central Lampung

The COVID-19 pandemic in 2019 posed a significant threat to public health, resulting in numerous fatalities. In response, the central and local government of Indonesia formulated policies aimed to control the spread of the virus. This research analyzed the enforcement of administrative sanctions for violations of COVID-19 health protocols in Central Lampung, Indonesia using a combination of normative juridical research methods and empirical legal research. Data were obtained by analyzing relevant literature, statutory regulations, and interviews conducted within Central Lampung Regency. The findings reveal that the implementation of COVID-19 health protocols in the region has been successfully conducted based on the Presidential Instruction No. 6 of 2020 and Regional Regulation No. 10 of 2020 at the local level. Administrative law enforcement against violations primarily involves initial verbal warnings, followed by escalated sanctions such as fines and, more severely, revocation of business permits, although the latter is infrequently applied. This research underscores the critical role of structured legal frameworks and responsive governance in managing public health crises.

Tranexamic Acid vs Adrenaline for Controlling Iatrogenic Bleeding During Flexible Bronchoscopy: A Double-Blind Randomized Controlled Trial

The most commonly used topical hemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on use of other agents such as tranexamic acid (TXA) for this purpose are limited. Is TXA effective and safe in controlling iatrogenic bleeding during FB compared with adrenaline? We conducted a cluster-randomized, double-blind, single-center trial in a tertiary teaching hospital. Patients were randomized in weekly clusters to receive up to three applications of TXA (100mg, 2mL) or adrenaline (0.2mg, 2mL, 1:10000) after hemostasis failure after three applications of cold saline (4 ° C, 5mL). Crossover was allowed (for up to three further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analog scale (VAS; 1= very mild, 10= severe). A total of 2,033 FBs were performed and 130 patients were randomized successfully to adrenaline (n= 65) or TXA (n= 65), whereas 12 patients had to be excluded for protocol violations (two patients from the adrenaline arm and 10 patients from TXA arm). Bleeding was stopped in 83.1%of patients (54/65) in both groups (P= 1). The severity of bleeding and number of applications needed for bleeding control were similar in both groups (adrenaline: mean VAS score, 4.9 ± 1.3 [n= 1.8 ± 0.8]; TXA: mean VAS score, 5.3 ± 1.4 [n= 1.8 ± 0.8]). Both adrenaline and TXA were more successful in controlling moderate bleeding (86.7%and 88.7%, respectively) than severe bleeding (40%and 58.3%, respectively; P= .008 and P= .012, respectively) and required more applications for severe bleeding (3.0 ± 0 and 2.4 ± 0.5, respectively) than moderate bleeding (1.7 ± 0.8 and 1.7 ± 0.8, respectively) control (P= .006 and P= .002, respectively). We observed no drug-related adverse events in either group. We found no significant difference between adrenaline and TXA for controlling noncatastrophic iatrogenic endobronchial bleeding after cold saline failure, adding to the body of evidence that TXA can be used safely and effectively during FB. ClinicalTrials.gov; No.: NCT04771923; URL: www. gov.

Bronchial reactivity to inhaled hypertonic saline solutions in children with cystic fibrosis

Background. Inhaled hypertonic saline solutions (IHSS) are included in the list of mandatory prescriptions in the treatment of cystic fibrosis (CF). However, some patients with CF may develop bronchial hyperreactivity (BHR), which may be the cause of violation of the treatment protocol. The purpose is to study the state of bronchial reactivity to IHSS and its dependence on the clinical, functional and microbiological features of CF course in children. Materials and methods. Forty children with CF were examined. All of them underwent general clinical, molecular genetic, laboratory and microbiological examination. Instrumental methods included spirometry, measurement of fractional exhaled nitric oxide, X-ray and computer tomography of the chest. To determine the individual tolerance of inhalations of hypertonic sodium chloride solution (HSCS), the research protocol proposed by E.P. Dellon et al. was used. Results. According to the results of the research protocol, 17 (42.5 %) patients with CF had BHR to HSCS. The highest frequency of BHR was found in children with a severe CF course. There was no dependence of BHR in CF patients on allergic pathology and a burdened allergic history. Assessment of the tolerance of HSCS before prescribing basic therapy is important. Early functional signs of BHR, which may require the preventive administration of short-acting β2-agonists when using HSCS in children with CF, are as follows: reduction in forced expiratory volume in 1 second by 7 % and maximal expiratory flow at 25 % by 6 % when using 3% HSCS. Conclusions. The presence of BHR in patients with CF may interfere with adequate basic therapy by inhalation. The prescription of IHSS to patients with CF should be personalized with the determination of individual sensitivity of a person to predict a positive therapeutic effect.

Predictors of poor outcome in critically ill patients with COVID-19 pneumonia treated with extracorporeal membrane oxygenation.

IntroductionWe aimed to identify risk factors associated with ICU mortality in critically ill patients with COVID-19 pneumonia treated with Extracorporeal membrane oxygenation (ECMO). We also aimed to assess protocol violations of the local eligibility criteria of ECMO initiation.MethodsAll 31 consecutive adult patients with confirmed COVID-19 pneumonia admitted to ICU and treated with ECMO from March 13th 2020 to 8 December 2021 were enrolled. Eligibility criteria for ECMO initiation were: P/F-ratio<50 mmHg >3 hours, P/F-ratio<80 mmHg >6 hours or pH<7.25 + PaCO2>60 mmHg >6 hours, despite maximal protective invasive ventilation. Primary outcome was ICU mortality. Univariate logistic regression analyses were performed to identify predictors of ICU mortality.Results12 out of 31 patients (38.7%) did not survive ECMO treatment in ICU. Half of the non-survivors suffered from acute kidney failure compared to 3 out of 19 survivors (15.79%) (p = .04). Half of the non-survivors required CRRT treatment versus 1 patient in the survivor group (5.3%) (p < .01). Higher age (2.45 (0.97–6.18), p = .05), the development of AKI (5.33 (1.00–28.43), p = .05), need of CRRT during ICU stay (18.00 (1.79–181.31), p = .01) and major bleeding during ECMO therapy (0.51 (0.19–0.89), p < .01) were identified to be predictors of ICU mortality.ConclusionAlmost 60% of patients could be treated successfully with ECMO with sustained results at 3 months. Predictors for ICU mortality were development of AKI and need of CRRT during ICU stay, higher age category and major bleeding. Inadvertent ECMO allocation was noted in almost one in five patients.

Whither the ECOWAS free movement protocols? Pandemic nationalism, borders, and migration in West Africa

The Covid-19 pandemic border closure policy and other anti-migrant policies in 2020 have become another basis for flaunting the ECOWAS free movement protocols by member states now referred to as pandemic nationalism. Although not limited to (West) Africa, pandemic nationalism reinforces the inability of ECOWAS to demonstrate supranationalism and ensure harmonization of Covid-19 trans-border policies among its members. Consequently, member states were unilaterally imposing conflicting or uncoordinated Coronavirus border closure policy without recourse to the protocols. Thus, the pandemic border closure policy has only exacerbated pre-existing trajectories which have serious implications for visa-free, border-free, and borderless West Africa as well as cross-border migration. These challenges are often attributed to colonial borders. This article has been able to adequately demonstrate that the Covid-19 pandemic has deepened nationalism which has, in turn, increased violation of ECOWAS free movement protocols through uncoordinated and reprisal border closure in which nationalism has trumped regionalism. The study is essentially qualitative, descriptive, analytical, and empirical.

Efficacy and Safety of Standardized Protocol of CPAP Therapy for Full-Term Newborns in Delivery Room at Transient Tachypnea: Clinical Trial with Historical Control

Background. Nowadays there is no consensus on the tactics and optimal protocol for Continuous Positive Airway Pressure (СРАР) at transient tachypnea of newborns (TTN) in delivery room.Objective. The aim of the study is to examine the efficacy and safety of standardized protocol of CPAP therapy for newborns with TTN in delivery room.Methods. The clinical study (implementation of standardized CPAP protocol) included full-term infants (gestational age — 37–41 weeks) with diagnosed TTN and CPAP therapy during first 60 minutes of life. Similar inclusion criteria were applied for the historical control group (born within previous year for whom CPAP was implemented according to “usual” protocol). Initiation of mononasal CPAP in main group was carried out when respiratory disorders were assessed according to Downes scale ≥ 3 points with control points at 20–40–60 minutes via the same scale, in control group at ≥ 4 points — for all cases, and according to the doctor's decision at 1–3 points. Mean airway pressure was maintained at 8 and 5–10 cm H2O, CPAP duration was 20–60 and 5–30 min, respectively. The major endpoints: the frequency of patient transfer from delivery room to intensive care unit or hospitalization to the neonatal pathology department, as well as total period of hospitalization. Moreover, frequency of invasive manipulations (intravenous catheterization, parenteral feeding), antibacterial therapy, cerebral injuries (cerebral ischemia, intracerebral hemorrhage), nasal passages injuries, pneumothorax (in the first 24 hours of life) were recorded during the entire hospitalization period.Results. 140 newborns with TTN were included in the clinical study, 30 were excluded from the study, specifically 13 due to violation of the CPAP protocol. The historical control group included 165 newborns. This groups were comparable for most baseline (before the start of CPAP) indicators except for maternal COVID-19 frequency during pregnancy and twin newborns frequency. This groups were comparable for most baseline (before the start of CPAP) indicators except for the frequency of maternal COVID-19 cases during pregnancy and the frequency of twin newborns. Hospitalization rate in intensive care units (18.2 versus 70.3%; p &lt; 0.001) and neonatal pathology departments (31.8 versus 80.0%; p &lt; 0.001), as well as total period of hospitalization (3 versus 10 days; p &lt; 0.001) were lower in the standardized CPAP therapy group. Lower frequency of invasive manipulations, antibacterial therapy, and cerebral ischemia was recorded in this group. The safety of СРАР administration in delivery room was confirmed by the absence of nasal passages injuries in both groups, as well as comparable frequency of pneumothorax.Conclusion. The use of standardized CPAP protocol in delivery room for full-term newborns with TTN had higher rate of favorable hospitalization outcomes. Study limitations require validation of all the findings in independent studies.

Racial and Ethnic Differences in Amyloid PET Positivity in Individuals With Mild Cognitive Impairment or Dementia

Racial and ethnic groups with higher rates of clinical Alzheimer disease (AD) are underrepresented in studies of AD biomarkers, including amyloid positron emission tomography (PET). To compare amyloid PET positivity among a diverse cohort of individuals with mild cognitive impairment (MCI) or dementia. Secondary analysis of the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS), a single-arm multisite cohort study of Medicare beneficiaries who met appropriate-use criteria for amyloid PET imaging between February 2016 and September 2017 with follow-up through January 2018. Data were analyzed between April 2020 and January 2022. This study used 2 approaches: the McNemar test to compare amyloid PET positivity proportions between matched racial and ethnic groups and multivariable logistic regression to assess the odds of having a positive amyloid PET scan. IDEAS enrolled participants at 595 US dementia specialist practices. A total of 21 949 were enrolled and 4842 (22%) were excluded from the present analysis due to protocol violations, not receiving an amyloid PET scan, not having a positive or negative scan, or because of small numbers in some subgroups. In the IDEAS study, participants underwent a single amyloid PET scan. The main outcomes were amyloid PET positivity proportions and odds. Data from 17 107 individuals (321 Asian, 635 Black, 829 Hispanic, and 15 322 White) with MCI or dementia and amyloid PET were analyzed between April 2020 and January 2022. The median (range) age of participants was 75 (65-105) years; 8769 participants (51.3%) were female and 8338 (48.7%) were male. In the optimal 1:1 matching analysis (n = 3154), White participants had a greater proportion of positive amyloid PET scans compared with Asian participants (181 of 313; 57.8%; 95% CI, 52.3-63.2 vs 142 of 313; 45.4%; 95% CI, 39.9-50.9, respectively; P = .001) and Hispanic participants (482 of 780; 61.8%; 95% CI, 58.3-65.1 vs 425 of 780; 54.5%; 95% CI, 51.0-58.0, respectively; P = .003) but not Black participants (359 of 615; 58.4%; 95% CI, 54.4-62.2 vs 333 of 615; 54.1%; 95% CI, 50.2-58.0, respectively; P = .13). In the adjusted model, the odds of having a positive amyloid PET scan were lower for Asian participants (odds ratio [OR], 0.47; 95% CI, 0.37-0.59; P < .001), Black participants (OR, 0.71; 95% CI, 0.60-0.84; P < .001), and Hispanic participants (OR, 0.68; 95% CI, 0.59-0.79; P < .001) compared with White participants. Racial and ethnic differences found in amyloid PET positivity among individuals with MCI and dementia in this study may indicate differences in underlying etiology of cognitive impairment and guide future treatment and prevention approaches.

Prevalence of pulmonary embolism among patients presenting to emergency department for hemoptysis

Abstract Background Although hemoptysis is a well known symptom of presentation of pulmonary embolism (PE), and it is included in different diagnostic scores for PE, the prevalence of PE in patients with hemoptysis and the yield of evidence based PE diagnostic pathway in these patients has not been specifically investigated. Objectives To determine the prevalence of PE and the yield (n° of positive tests/n° of tests), the efficiency (the proportion of patients in whom PE could be considered to be excluded) and the failure rate (the false negative rate) of the classic diagnostic algorithm for PE in patients with hemoptysis. Methods Unselected patients presenting with hemoptysis to 7 italian EDs were prospectively enrolled in a diagnostic multicenter study. Pre-test clinical probability for PE was assessed using the 2-level Wells score and the results of D-dimer testing using age-adjusted cutoffs. Presence of PE was evaluated by CT pulmonary angiogram (CTPA), when ordered as part of the clinical assessment by the treating ED physician, or by one month follow-up data. Results Out of 327 adult patients presenting to ED with hemoptysis, 15 (4.6%) were excluded because of diagnostic protocol violation and absence of one month follow-up. Among 312 included patients, PE was detected at presentation in 15 patients (4.8%; 95% confidence interval [CI]: 2.72–7.81%). During follow-up, 5 patients died (1.6%; 95% CI: 0.52%-3.7%) not due to PE. Among 165 patients with a “likely” score or a high D-dimer, 13 (7.9%; 95% CI: 4.72–13.8%) had PE. The efficiency was 32.8% and the failure rate was 1.7% in patients tested by D-dimer. Conclusions PE seems an uncommon cause of hemoptysis among patients presenting to the ED and the yield of classic diagnostic algorithm is low. PE-screening in patients with hemoptysis deserves further investigation aimed at improving the diagnostic yield. Funding Acknowledgement Type of funding sources: None.

A decentralized analysis of multiparty protocols

Protocols provide the unifying glue in concurrent and distributed software today; verifying that message-passing programs conform to such governing protocols is important but difficult. Static approaches based on multiparty session types (MPST) use protocols as types to avoid protocol violations and deadlocks in programs. An elusive problem for MPST is to ensure both protocol conformance and deadlock-freedom for implementations with interleaved and delegated protocols. We propose a decentralized analysis of multiparty protocols, specified as global types and implemented as interacting processes in an asynchronous π -calculus. Our solution rests upon two novel notions: router processes and relative types . While router processes use the global type to enable the composition of participant implementations in arbitrary process networks, relative types extract from the global type the intended interactions and dependencies between pairs of participants. In our analysis, processes are typed using APCP, a type system that ensures protocol conformance and deadlock-freedom with respect to binary protocols, developed in prior work. Our decentralized, router-based analysis enables the sound and complete transference of protocol conformance and deadlock-freedom from APCP to multiparty protocols. • A new analysis of multiparty protocols expressed as Multiparty Session Types (MPST). • The analysis relies on APCP, a typed process calculus for binary sessions with asynchronous communication. • Novel notions: router processes (which connect implementations) and relative types (protocols between pairs of participants). • The analysis ensures protocol-conformance and deadlock-freedom; it also supports delegation and interleaving. • Process implementations can have arbitrary topologies; decentralized and centralized networks arise as instances.