Publication Of Guidelines Research Articles

Implementation of Recommendations on the Use of Corticosteroids in Severe COVID-19

Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary objectives were to evaluate the association between the timing of publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (June 2020) and the WHO guidelines for corticosteroids (September 2020) and the temporal trends observed in corticosteroid use by region and to describe the geographic distribution of the recruitment in clinical trials that informed the WHO recommendation. This prospective cohort study of 434 851 patients was conducted between January 31, 2020, and September 2, 2022, in 63 countries worldwide. The data were collected under the auspices of the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC)-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Analyses were restricted to patients hospitalized for severe COVID-19 (a subset of the ISARIC data set). Corticosteroid use as reported to the ISARIC-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Number and percentage of patients hospitalized with severe COVID-19 who received corticosteroids by time period and by WHO geographic region. Among 434 851 patients with confirmed severe or critical COVID-19 for whom receipt of corticosteroids could be ascertained (median [IQR] age, 61.0 [48.0-74.0] years; 53.0% male), 174 307 (40.1%) received corticosteroids during the study period. Of the participants in clinical trials that informed the guideline, 91.6% were recruited from the United Kingdom. In all regions, corticosteroid use for severe COVID-19 increased, but this increase corresponded to the timing of the RECOVERY trial (time-interruption coefficient 1.0 [95% CI, 0.9-1.2]) and WHO guideline (time-interruption coefficient 1.9 [95% CI, 1.7-2.0]) publications only in Europe. At the end of the study period, corticosteroid use for treatment of severe COVID-19 was highest in the Americas (5421 of 6095 [88.9%]; 95% CI, 87.7-90.2) and lowest in Africa (31 588 of 185 191 [17.1%]; 95% CI, 16.8-17.3). The results of this cohort study showed that implementation of the guidelines for use of corticosteroids in the treatment of severe COVID-19 varied geographically. Uptake of corticosteroid treatment was lower in regions with limited clinical trial involvement. Improving research diversity and representativeness may facilitate timely knowledge uptake and guideline implementation.

Building Public Open Space Design and Management Strategy in Urban Waterfront Areas—A Case Study of New York Water Street POPS

The construction of building public open space in urban waterfront areas is one of the important issues for future development. Based on the study of the development history of the private public space (POPS) design guidance and control of New York City's Water Street, we analyze the identify approval and incentive zoning programme, design guidelines and quantitative standards, and post-build operation and supervision of POPS. Analyzing the guidance and control strategies of the design guidance and control system in different periods of time and in different social contexts. Combined with China's waterfront design regulations and public open space guidelines, the article propose a framework for waterfront public open space design and control strategies that are suitable for China.

Current Findings on the Spectrum of Neuronal Autoantibodies Associated with Psychotic Disorders

Background: Neural autoantibodies are observed in a subtype of psychotic disorders ranging from first-episode psychosis to schizophrenia. The clinical spectrum has so far been incompletely described, as new neuronal autoantibodies are emerging in the context of psychosis. This review is dedicated to describing the current spectrum of neural autoantibodies associated with psychotic disorders.
 Methods: In our narrative review, we searched for neural autoantibodies addressed in the PubMed database in the last 15 years focusing on the last three years after publication of the international guidelines for autoimmune psychosis. We relied on small and large cohort studies and case series descriptions related to neural autoantibodies in psychotic disorders.
 Results: Mainly neural autoantibodies against membrane surface structures such as N-Methyl-D-aspartate receptors (NMDAR) and against intracellular targets are present in psychotic disorders, but also in healthy controls. There is current suspicion that these neuronal autoantibodies (ie., NMDAR autoantibodies) play a potentially relevant role in the development of brain pathologies in psychotic disorders, especially when detected in cerebrospinal fluid. Autoantibodies against cell adhesion molecules and synaptic proteins such as neuronal cell adhesion molecule 1 (NCAM1) and antigen neurexin 1 alpha (NRXN1)-alpha occur in schizophrenia, but not in controls, suggesting that these are highly disease-specific antibodies. These lines of evidence are further supported by animal-model evidence showing a role of these autoantibodies in brain pathology and the development of schizophrenia-like symptoms.
 Conclusions: In recent years, a new landscape of potentially relevant neural autoantibodies has emerged in a subtype of psychotic disorders. Their significance remains unclear. Large-scale investigations should particularly investigate what triggers the pathogenicity of these autoantibodies, as they probably do not cause the psychotic disorder per se, but might be involved as one factor in the immunopathophysiology. Psychotic disorders remain elusive, and differential diagnosis is required to determine the role neural autoantibodies play in the manifestation of psychoses.

Initiation of opioid agonist therapy after hospital visits for opioid poisonings in Ontario.

Emergency department visits and hospital admissions for opioid toxicity are opportunities to initiate opioid agonist therapy (OAT), which reduces morbidity and mortality in patients with opioid use disorder (OUD). The study objectives were to evaluate OAT initiation rates after a hospital encounter for opioid toxicity in Ontario, Canada, and determine whether publication of a 2018 Canadian OUD management guideline was associated with increased initiation. We conducted a retrospective, population-based serial cross-sectional study of hospital encounters for opioid toxicity among patients with OUD between Jan. 1, 2013, and Mar. 31, 2020, in Ontario, Canada. The primary outcome was OAT initiation (methadone, buprenorphine-naloxone, or slow-release oral morphine) within 7 days of discharge, measured quarterly. We examined the impact of the release of the OUD management guideline on OAT initiation rates using Autoregressive Integrated Moving Average models. Among 20 702 hospital visits for opioid toxicity among patients with OUD, the median age was 35 years, and 65.1% were male. Over the study period, the percentage of visits leading to OAT initiation within 7 days rose from 1.7% or less (Q1 2013) to 5.6% (Q1 2020); however, the publication of the Canadian OUD management guideline was not associated with a significant increase in these rates (0.14% slope change, 95% confidence interval -0.11% to 0.38%; p = 0.3). Among hospital encounters for opioid toxicity, despite rising prevalence over time, only 1 in 18 patients were dispensed OAT within a week of discharge in early 2020. These findings highlight missed opportunities to initiate therapies proven to reduce mortality in patients with OUD.

Updated NICE Cardiotocograph (CTG) Guideline: Is it Suspicious or Pathological?

Cardiotocograph (CTG) trace was introduced into clinical practice in 1960s as a tool to record the changes in the fetal heart rate (cardio) in response to ongoing uterine contractions (toco). The intention was to timely recognise the features of fetal decompensation so that immediate action could be taken to avoid hypoxic ischaemic encephalopathy (HIE) and/ or intrapartum hypoxia-related perinatal deaths, without increasing unnecessary operative interventions to the mother. However, very unfortunately, unlike other tools in clinical medicine, CTG was introduced into clinical practice without any randomised controlled trials or robust scientific studies not only to confirm its effectiveness, but to determine the CTG features which actually reflected fetal central organ oxygenation. This chasm of deficiency of knowledge of fetal physiology created a vacuum of understanding regarding what features were reflecting fetal compromise. Regrettably, this vacuum was soon filled by prominent obstetricians from national societies who were presumed to have the knowledge, but they began the arduous journey of classifying decelerations which are normal fetal cardioprotective reflexes, and they misclassified them as signs of “fetal distress”. Classification of these decelerations based on the observed morphology into “reassuring” and “nonreasoning” categories has resulted in disastrous consequences for women and babies. In the UK, since the publication of the first CTG guideline in 2001, due to continuing lack of knowledge and confusion, these guidelines were repetitively revised in 2007, 2014, 2017 and 2022. Despite the international consensus guidelines of physiological interpretation of CTG produced by 44 CTG experts from 14 countries which recommended classification of CTG traces based on the type of fetal hypoxia and fetal response to stress, the latest revised guideline produced by the National Institute of Health and Care Excellence (NICE), had continued the illogical approach of grouping arbitrary features into different categories and then randomly combining them to classify the CTG traces into “Normal, Suspicious and Pathological”. Therefore, all practising clinicians who are focussed on protecting their patients from harm have a responsibility to ask the question whether the revised NICE CTG Guideline itself is suspicious or pathological from a patient safety perspective.

Microsatellites’ mutation modeling through the analysis of the Y-chromosomal transmission: Results of a GHEP-ISFG collaborative study

The Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) organized a collaborative study on mutations of Y-chromosomal short tandem repeats (Y-STRs). New data from 2225 father-son duos and data from 44 previously published reports, corresponding to 25,729 duos, were collected and analyzed. Marker-specific mutation rates were estimated for 33 Y-STRs. Although highly dependent on the analyzed marker, mutations compatible with the gain or loss of a single repeat were 23.2 times more likely than those involving a greater number of repeats. Longer alleles (relatively to the modal one) showed to be nearly twice more mutable than the shorter ones. Within the subset of longer alleles, the loss of repeats showed to be nearly twice more likely than the gain. Conversely, shorter alleles showed a symmetrical trend, with repeat gains being twofold more frequent than reductions. A positive correlation between the paternal age and the mutation rate was observed, strengthening previous findings. The results of a machine learning approach, via logistic regression analyses, allowed the establishment of algebraic formulas for estimating the probability of mutation depending on paternal age and allele length for DYS389I, DYS393 and DYS627. Algebraic formulas could also be established considering only the allele length as predictor for DYS19, DYS389I, DYS389II-I, DYS390, DYS391, DYS393, DYS437, DYS439, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS533, DYS576, DYS626 and DYS627 loci. For the remaining Y-STRs, a lack of statistical significance was observed, probably as a consequence of the small effective size of the subsets available, a common difficulty in the modeling of rare events as is the case of mutations. The amount of data used in the different analyses varied widely, depending on how the data were reported in the publications analyzed. This shows a regrettable waste of produced data, due to inadequate communication of the results, supporting an urgent need of publication guidelines for mutation studies.

Conflict of Interest: An Epidemic Dilemma Within the South African Public Procurement System

Background: Challenges of the South African public procurement system continues unabated to make visible footprints in the yearly Auditor-General’s reports. At the centre of the challenges is the failure to comply with the legislative framework regulating public procurement resulting in irregular expenditure. Compliance failures are at the root of evil deeds and misconduct in the South African public sector.Setting: The existence of a plethora of legislative frameworks, polices and standard operating procedures and the yearly reports of the Auditor-General leaves one pondering in relation to the difficulty for procurement officials to adhere to these prescripts. Aim: It against this notion that this conceptual paper gives an analysis of the impact of conflict of interests as suspect in chief on failure by procurement officials to adhere on procurement regulations. Of essence is to examine causal factors and inherent consequences which in most instances is conflicting interest by public officials.Method: This paper analyses secondary data with regard to conflict of interest with in the South African public procurement system. This is done by means of literature and government documentation.Conclusion: This paper concludes that the concept of conflict of interest is not new within the procurement space, yet procurement officials still grapple on how to effectively deal with it whenever it arises. This therefore calls for reform in procurement processes especially in ensuring consequentialism for wrongdoers.Contribution: The paper contributes towards the shaping of public procurement policies and ethical guidelines in all spheres of government. This paper further contributes to the body of knowledge considering that it will unearth critical dimensions of conflict of interests particularly for the public sector.

Current Pediatric Tertiary Care Practices Following Adenotonsillectomy: An Update.

Adenotonsillectomy is a common procedure performed in children, and the practice patterns at academic centers have been evolving with the publication of updated societal guidelines. In this study, we assess perioperative practice patterns at tertiary care children's hospitals for children undergoing adenotonsillectomy. A cross-sectional 18-question survey distributed in July of 2022 recruited responses through August 25, 2022. The division chiefs of 70 pediatric otolaryngology groups at tertiary care children's hospitals across the United States and Canada were surveyed. Division chiefs submitted survey responses on behalf of the group practice patterns for children undergoing adenotonsillectomy. The main measure was survey responses from the division chiefs of pediatric otolaryngology reporting group practice. The survey response rate was 46%. Eighty-eight percent of groups reported an official adenotonsillectomy admission policy. Commonly reported admission criteria included age (93%) and obesity (59%). Eighty-eight percent of groups defined severe obstructive sleep apnea as apnea-hypopnea index ≥10. Only 41% of groups required a child to be observed sleeping on room air prior to ambulatory discharge. Ninety-seven percent of groups reported routinely obtaining preoperative polysomnography in a variety of clinical settings. Many children's hospitals report an official admission policy following adenotonsillectomy. Despite a decade passing since the initial publication of the American Academy of Otolaryngology-Head and Neck Surgery clinical practice guidelines, there remains great variability in the practice patterns for both preoperative polysomnography and postoperative monitoring and admission. These results highlight an opportunity for an improved unified approach to perioperative pediatric adenotonsillectomy practice. 5 Laryngoscope, 134:2931-2936, 2024.

Workshop “Guidelines for Successful Publishing of Scientific Research in Authority Journalsˮ

Workshop “Guidelines for Successful Publishing of Scientific Research in Authority Journalsˮ

Community Engagement in Behavioral Medicine: A Scoping Review.

Behavioral medicine has made key contributions toward improving health outcomes. Engaging community partners in research is critical to addressing persistent health inequities. The aim of this scoping review was to explore how researchers engaged community partners within the field of behavioral medicine research from 2005 to 2023. Publication databases and gray literature were searched for research that engaged community partners to address questions relevant to behavioral medicine. Articles were screened by title and abstract, and then by full text. Articles meeting the inclusion criteria were coded using the framework provided by the Engagement Navigator to identify engagement approaches, methods, and tools and when they were used during the research. Of 1486 articles initially identified, 58 met the inclusion criteria. Most articles used well-known approaches (e.g., community-based participatory research; 67%), methods (e.g., advisory committees; 59%), and tools (e.g., interviews; 41%), and engaged with healthcare service providers (62%) and/or patients (53%). Community partners were most often included in research planning and design (79%), and less often in dissemination (45%). Community engagement has considerable potential to address health inequities. Our assessment of the approaches, methods, and tools used by behavioral medicine researchers to engage with a diverse range of community partners points toward promising strategies for enhancing the impact of community engagement. Researchers should incorporate explicit descriptions of community engagement strategies in publications, an outcome that could be facilitated by clear publishing guidelines, structured reporting tools, and clear messaging from funders about the value of community engagement in behavioral medicine research.

Food protein-induced enterocolitis syndrome (FPIES): Beyond the guidelines.

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE) cell mediated food allergy that can cause severe symptoms and is considered an allergic emergency. To describe FPIES epidemiology and appraise the approach to diagnosis and management. A review of the relevant articles published in the peer-reviewed journals since the publication of the First International FPIES Consensus Guidelines in 2017. FPIES is estimated to affect 0.51-0.9% of children and 0.22% of adults in the United States. It typically presents with protracted, projectile vomiting, which occurs within 1-4 hours of ingesting culprit foods, sometimes followed by diarrhea within 24 hours of ingestion. In ∼15-20% of severe cases, patients go into hypovolemic or distributive shock. In chronic FPIES, infants may have failure to thrive and weight loss. The most common triggers include cow's milk, oat, rice, and avocado, with egg and peanut being more frequently reported. Examples of other common fruit and vegetable triggers include banana, apple, and sweet potato. FPIES can be classified into acute, chronic, adult-onset, or atypical subtypes. FPIES is associated with comorbid atopic conditions of IgE-mediated food allergy, atopic dermatitis, asthma, allergic rhinitis, and eosinophilic esophagitis. The natural history of infantile FPIES is generally favorable, with the exception of fish FPIES. Seafood FPIES in adults has low rates of resolution over 3-5 years. Correctly identifying FPIES can be challenging because there are no specific biomarkers for diagnosis and the constellation of symptoms may mimic those of infectious enteritis or sepsis. Management relies on dietary food avoidance, periodic re-evaluations for tolerance with oral food challenges, and management of acute reactions with rehydration and antiemetic ondansetron. Although the pathophysiology of FPIES remains poorly understood, underlying mechanisms such as cytokine release, leukocyte activation, and impaired gastrointestinal mucosal barrier function may act as cornerstones for further research. Prevention, laboratory diagnostic testing, and strategies to accelerate tolerance development are urgent unmet needs in FPIES.

Assessing the readability of open data portals: a case study of Open Data Pakistan

Open data portals have been implemented in numerous countries to provide accessible, usable, and reproducible data. This study aims to assess the readability of datasets from Open Data Pakistan. Using the URL (https://opendata.com.pk/) in an online readability checking tool, six well-known readability formulas were employed, including Flesch Kincaid Reading Ease, Flesch Kincaid Grade Level, Gunning Fog Score, Smog Index, Coleman Liau Index, and Automated Readability Index. The average score of each formula was calculated to analyze the standard readability of the open data portal. Additionally, the website was explored to evaluate the overall status of open datasets, showcases, and features like "Connect" on Open Data Pakistan. The findings indicated that the Open Data Pakistan website has a reading difficulty, scoring an average of 47.4 out of 100, making it challenging for the general public to read. However, the overall analysis suggested that the readability status of open data in Pakistan is satisfactory. These results offer insights into improving the readability of open data for enhanced citizen participation and informed decision-making. Moreover, the study has implications for policymakers and stakeholders regarding the readability of Open Data Pakistan, emphasizing the importance of considering readability in open data publication policies and guidelines, with a recommendation to decrease the percentage of open data portals categorized as hard to read.

Impact of the 2014 NHLBI Hydroxyurea Guidelines on Cerebrovascular Events in Sickle Cell Disease

Background: Cerebrovascular disease (CVD) is a common cause of morbidity in patients with sickle cell disease (SCD). An estimated 37% of children with SCD have silent cerebral infarcts (SCI) by age 14, leading to increased stroke risk and neurocognitive impairment. In the DISPLACE trial (Kanter et al, 2021), 2.9% of patients had abnormal cerebral blood flow as measured on transcranial Doppler ultrasound (TCD). The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend hydroxyurea (HU) for all patients with SCD-SS and SCD-Sβ 0 starting at age 9 months, a significant shift from prior practice. In patients who have already developed TCD abnormalities, HU is protective against stroke and CVD progression. The real-world impact of universal early HU on the development of CVD, particularly on SCI, is not well defined . We hypothesize that the 2014 guidelines led to an increase in HU use and a reduction in the initial development of CVD. Methods: We performed a single center, retrospective cohort study investigating trends in HU prescriptions and CVD before and after the publication of the 2014 NHLBI guidelines. Patients with SCD-SS and SCD-Sβ 0 who initiated hematology care at the Children's Hospital of Philadelphia between 2009 and 2023 were identified using an institutional registry. Incident HU was defined as the first outpatient HU prescription in patients with a minimum of two orders. Incident CVD was defined as a composite outcome consisting of the first documentation of: abnormal TCD, brain magnetic resonance imaging (MRI) with silent infarct, or overt ischemic stroke. Patients with known CVD before care initiation, prematurity < 28 weeks gestational age, or non-SCD neurologic disease were excluded. For time-to-HU analysis, patients with HU prescriptions before enrollment at our center also were excluded. Patients were followed from their first hematology visit until the outcome of interest or censoring. Censoring criteria included loss to follow up, transition of care, or bone marrow transplant. All brain MRI and TCD reports were manually reviewed. Ages at HU initiation pre- and post- guideline were compared using the Wilcoxon rank-sum test . Times to 1) HU and 2) CVD were summarized using Kaplan-Meier estimators, with the guideline publication date of September 1, 2014 incorporated as a time-varying exposure. Unadjusted associations were calculated using a Cox proportional hazard regression. Results: A total of 446 patients met inclusion criteria and contributed to analyses. Median age at baseline was 2.4 months, and median duration of follow-up was 5.0 years (IQR: 2.3-8.7). Most patients (430/446, 96%) had SCD SS, and 51% were male. The proportion of patients ever prescribed HU increased with time (Fig 1), with a peak prevalence of 82% in 2022. Of 385 patients not exposed to HU at baseline, 277 (72%) were prescribed HU during study follow-up. Incident HU prescriptions significantly increased after NHLBI guideline publication (HR 3.40, CI: 2.50 to 4.63, p < 0.001) with an older age at HU initiation before (median 4.0 y, IQR 2.5-7.7) than after (median 2.9 y, IQR 1.1-5.8) publication of the guideline (p = 0.002). Over a total of 2,395 person-years of follow-up, 66 incident CVD outcomes occurred in this longitudinal cohort, corresponding to a cumulative incidence of 14.8%. These events included 53 SCI, 10 abnormal TCD, and 3 overt ischemic strokes. CVD outcome occurrence was lower after guideline publication than before (HR 0.58, CI: 0.32-1.05), though the association did not reach statistical significance (p = 0.071, Fig. 2). Discussion: After the NHLBI guideline publication, HU prescriptions increased significantly at our center.Our data suggest that the 2014 guideline-directed care may have led to a greater than 40% reduction in CVD, though this reduction was not statistically significant in our small sample size. Despite guideline recommendations and strong evidence for the role of HU in reducing pain and acute chest syndrome, few patients across the United States are prescribed HU therapy. Adherence and care continuity challenges further lessen the number of patients benefitting from HU. Evidence of efficacy of early and universal HU in CVD prevention would strengthen guideline recommendations and improve clinical care in patients with SCD. Ongoing analysis includes an expanded cohort and adjustment for clinical covariates to better examine the direct impact of early HU on CVD.

Appropriateness of Immunosuppression and Blood Product Utilization in Acquired Hemophilia A: A Multicentre Provincial Practice Audit

Introduction: Acquired hemophilia A (AHA) is a life-threatening bleeding disorder associated with significant morbidity and mortality. Despite publication of international consensus guidelines, quality of care and guideline adherence have not been examined. While some jurisdictions have reference centres for AHA management, in Canadian provinces outside of Quebec, AHA is managed in both hemophilia treatment centres (HTCs) and community hospitals. We performed a multicentre practice audit in a Canadian province to assess use of immunosuppressive therapy (IST), blood product utilization, and evaluate treatment burden and outcomes. Methods: We included adults diagnosed with AHA (January 2000-December 2021) in Alberta, Canada, and examined the following quality of care indicators: delayed IST initiation from diagnosis, corticosteroid use alone in high-risk AHA (FVIII <0.01 IU/ml or FVIII inhibitor >20 BU/ml), cyclophosphamide use in low-risk patients (FVIII ≥0.01 IU/ml and inhibitor ≤20 BU/ml), prolonged cyclophosphamide use (>6 weeks), and inappropriate use of plasma, intravenous immunoglobulin (IVIG) and hemostatic products. Outcome measures included response, length of stay (LOS) and 30-day readmission. We evaluated treatment burden including frailty syndromes, increased level of care and hospitalization for treatment-related adverse events. Results: Of the 38 patients diagnosed with AHA, 25 (66%) were female, the median age was 74 years (IQR 61-81), and median Charlson comorbidity index was 5 (IQR 3-7). Cardiovascular comorbidities were common, including venous thromboembolism (5; 13%), atrial fibrillation (5; 13%), and myocardial infarction (4; 11%). Fifteen (39%) had ≥1 frailty syndromes, including functional dependence (6; 16%), dementia (6; 16%), falls/fractures (5; 13%), and depression/anxiety (3; 8%). Five (13%) patients required higher levels of care (long term care placement) following discharge. Twenty-one (55%) patients had high-risk disease and 17 (45%) had low-risk. In those with low-risk disease, 11 (29%) had inhibitor titres 5-20 BU/ml and 6 (16%) had inhibitors <5 BU/ml. Despite diagnostic delays ≥7 days from bleeding in 15 (39%), most received prompt initiation of IST (median 0 days [IQR 0-3] from diagnosis). First-line IST included: prednisone (38; 100%), cyclophosphamide (23; 61%), and rituximab (13; 34%). IVIG was prescribed in 5 (13%), out of keeping with guideline recommendations. We observed very high rates of first-line cyclophosphamide use in low risk AHA (11/17; 65%), including 4/6 with inhibitor titres <5 BU/ml (Table 1). First-line cyclophosphamide was also used in 3 reproductive-aged women. Prolonged courses of cyclophosphamide >6 weeks and >6 months were used in 21/23 (91%) and 7/23 (30%) patients, respectively. Two high-risk patients did not receive cyclophosphamide or rituximab-containing therapy. Of the 58 episodes of bleeding events, 41 (71%) were ISTH major bleeds. Fifteen (26%) bleeding events did not receive hemostatic therapy, whereas 27 (47%), 19 (33%), and 3 (5%) were treated with recombinant factor VIIa, activated prothrombin complex concentrates, and porcine FVIII, respectively. Dosing of bypassing agents was in keeping with guidelines. DDAVP and human FVIII were inappropriately used in 3/58 (5%) and 1 (2%) bleeding episodes, respectively. Most patients (24; 63%) received red cell transfusions with a median of 2 (IQR 0-7) units each. Five (13%) patients received a total of 18 units of plasma. Clinical responses included: complete remission (CR) in 30 (79%), partial remission in 3 (8%), and unevaluable due to early deaths in 5 (13%). All 5 patients who relapsed (13%) achieved second CR. The median LOS was 38 days (IQR 19-57) across 95 hospitalizations. The 30-day readmission rate was 24%. Reasons for admission included bleeding (50/95; 53%), infections (14/95; 15%), and other treatment side-effects (13/95; 14%). Conclusion: In this provincial cohort of AHA patients with high comorbidity and frailty, we identified gaps in quality of care including overuse of cyclophosphamide in patients with low-titre inhibitors, prolonged duration of cyclophosphamide, and inappropriate use of IVIG and plasma. Aggressive cytotoxic therapy predisposes patients to unnecessary risks of infections and malignancies. Our findings highlight the need for centralization of care in specialized centres and education initiatives.

Comparison of Alloimmunization in Pregnant People with Sickle Cell Disease Receiving Chronic Versus on-Demand Transfusions: A Multinational Study

Introduction Despite exceptional maternal morbidity and mortality risk, people with sickle cell disease (SCD) lack firm indications for chronic transfusion therapy (CTT) during pregnancy. Alloimmunization may cause hemolytic transfusion reactions and can limit the safety of future blood transfusions; thus it is a rationale for restricting CTT during pregnancy. Little data quantifies this risk. The 2020 American Society of Hematology (ASH) Guidelines for SCD TransfusionSupport recommend CTT in some pregnancies, but adoption in clinical practice is unknown. This study's purpose is to use a large two-center SCD pregnancy cohort to describe alloimmunization rates in SCD pregnancies treated with CTT vs on-demand transfusion (ODT) and to determine the fraction of SCD pregnancies meeting the ASH Guideline to initiate CTT in pregnancy. Methods We reviewed SCD pregnancies delivered at Mt. Sinai Hospital, Toronto (1990-2017) and Johns Hopkins Hospital (2000-2021). We collected data on transfusions and SCD complications before and during pregnancy, delivery, and fetal outcomes. Analyses classified subjects and pregnancies as receiving CTT or ODT. We defined CTT as pregnancies treated with scheduled, prophylactic transfusions; ODT as pregnancies transfused as-needed, including no transfusions. Sinai routinely matched transfusions for Rh and K antigens while Hopkins matched Rh only. Both centers provided extended matching if an alloantibody was detected. The first analysis included singleton pregnancies to primigravida subjects. We compared new alloantibody development, SCD complications, and pregnancy outcomes in CTT vs. ODT groups and in genotype stratified groups. We used Chi-squared and Wilcoxon rank-sum tests for categorical and continuous variables; p < .05 was significant. The second analysis included all cohort pregnancies and identified which met criteria for CTT per ASH Transfusion Guidelines which advise CTT for (A) severe SCD complications before or during pregnancy here defined by acute chest syndrome (ACS) or pain requiring acute care in the year before or during pregnancy, any history of venous thromboembolism (VTE), stroke, or multi-organ failure or (B) features of high-risk pregnancy, defined by multiple gestation, pre-eclampsia, gestational hypertension, cardiac comorbidities, or preterm labor history. Results Among 145singleton, primigravida pregnancies, more received ODT than CTT (119 ODT vs 26 CTT). Among ODT subjects 46/119 received at least one transfusion during pregnancy. CTT subjects had more severe SCD than ODT subjects before pregnancy (Table 1). During pregnancy, SCD severity did not differ (Table 2). Before pregnancy, 18 subjects were alloimmunized and did not differ by treatment group (6/26 CTT vs 12/119 ODT, p=0.07). During pregnancy, six subjects developed an alloantibody and did not differ by treatment group (1/26 CTT vs 5/119 ODT, p=0.93). Half (3/6) had a history of alloimmunization before pregnancy (1 CTT vs 2 ODT, p=0.27) and three did not (0 CTT vs 3 ODT, p=0.27). All subjects with new antibodies during pregnancy and historic alloimmunization developed anti-K antibodies (1 CTT, 2 ODT) at both sites. Those without alloimmunization history developed anti-Jkantibodies (3 ODT) at Sinai. In the secondary analysis, we included 299 pregnancies to 203 subjects. Among them, 249 pregnancies (83%) met at least one ASH Guideline criteria for initiating CTT. This included all CTT pregnancies (61/61, 39 subjects) and 79% of ODT pregnancies (188/238, 164 subjects), 46% of which received at least one transfusion during pregnancy (86/188). Conclusions In this SCD pregnancy cohort, alloimmunization rates were low and did not differ between those treated with CTT versus ODT. As alloimmunization events were inconsistent with institutional matching practices, new antibody development may be attributable to transfusions from outside hospitals or pregnancy-associated alloimmunization. Antigen matching per ASH Transfusion Guidelines avoids C, E, K and Jk alloimmunization. Scheduled transfusions may reduce emergency transfusion which increases alloimmunization risk. Finally, all CTT and 79% of ODT pregnancies met ASH Guideline criteria for CTT in pregnancy, however the cohort predates ASH Guideline publication. Guideline adherence may lead to increased use of CTT during pregnancy. More discriminating tools are needed to inform CTT use in SCD pregnancy.

A Shift Toward Early Oral Feeding in Acute Pancreatitis.

The 2018 American Gastroenterological Association (AGA) guidelines strongly recommended early oral feeding as tolerated in patients with acute pancreatitis (AP). We compare early oral feeding rates in AP patients hospitalized in the periods before (2013-2016, Period A) and after (2019-2020, Period B) publication of the AGA guidelines, hypothesizing increased adherence in Period B. We performed a retrospective cohort study of AP patients presenting to the emergency department during each period. Early oral feeding was defined as diet initiation within the first 48 hours of presentation. The cohort included 276 AP cases in period A and 104 in period B. A higher percentage of patients were offered early oral feeding during period B as compared to period A (70.2% vs. 43.5%). Similarly, more patients in period B were started on solid diet as compared to period A (34.6% vs. 20.3%). On multivariable regression analysis, the independent predictors of delayed oral feeding included early opioid analgesics use (OR 0.37), presence of pancreatic necrosis (OR 0.14), and organ failure (OR 0.33). More AP patients were initiated on early oral feeding in the period following the publication of the AGA guidelines. Opioid analgesics use, pancreatic necrosis, and organ failure were associated with delayed oral feeding.

Road Safety Audit (RSA) Guidelines of Selected Nations – a Comparative Review

One of the proactive preventive strategies for the global issue of road crashes is the Road Safety Audit (RSA). There are many advantages to using RSA, however, country-specific regulations often apply when it comes to conducting RSAs. The goal of this study was to compare the content of regulations in a sample of seven countries. Crucial indicators were examined and compared. The term ‘RSA’ was defined differently in each set of guidelines. Different project phases in various nations required the RSA methodology. The contents and coverage of the accompanying checklists or forms also varied. The documents unevenly stressed the team’s needs or the auditors’ qualifications. The legal liability issues received no attention from three of the seven guideline publications. The documents of two countries lacked any examples of RSA reports or case studies. The documents of some countries placed a strong focus on certain criteria but fell short in other areas. There was no RSA guideline document which may be referred to as best practice that accounted for the local circumstances and requirements. Improvements to guideline documents are suggested. This study, updated as of October 2023, will assist the road safety community, including transport officials, world banks, highway practitioners, road safety auditors, policymakers, urban planners and research scholars.

The street tree distribution across a streetscape reflects the social inequality of Latin American cities

Due to the ecosystem services they provide, street trees are fundamental for the quality of life and well-being of the urban human population. However, street trees are usually not equitably distributed across streetscapes, making some demographic groups most vulnerable to the consequences of a poorly managed street tree community. In this study, we evaluated if the socioeconomic characteristics of a large Latin American metropolis (wealth and density of older adults and children) are related to aspects describing characteristics of the street tree community (number of trees, beta diversity, canopy diameter, and proportion of native trees). Our street trees database is comprised of more than 250,000 trees and 559 species. Through a model selection approach, we observed that all socioeconomic characteristics relate to an aspect of the street tree community. The number of trees increased with wealth, but the highest densities of older adults were observed in regions with fewer trees. Canopy cover, conversely, decreased in wealthier neighborhoods and in regions with a higher density of children, while increasing with the density of older adults. Beta diversity of native trees also decreased with wealth. These results not only highlight the luxury effect across the streetscape but reflect the social inequality of Latin American cities: most people from both demographic groups live in regions with a less exuberant tree cover. Our approach can help identify the strengths and weaknesses regarding the plan and management of this street tree community, assisting in the definition of public policies and guidelines for a more sustainable and equitable urban landscape.

Trend of Outcome Metrics in Recent Out-of-Hospital-Cardiac-Arrest Research: A Narrative Review of Clinical Trials.

Cardiopulmonary resuscitation (CPR) research traditionally focuses on survival. In 2018, the International Liaison Committee on Resuscitation (ILCOR) proposed more patient-centered outcomes. Our narrative review assessed clinical trials after 2018 to identify the trends of outcome metrics in the field OHCA research. We performed a search of the PubMed database from 1 January 2019 to 22 September 2023. Prospective clinical trials involving adult humans were eligible. Studies that did not report any patient-related outcomes or were not available in full-text or English language were excluded. The articles were assessed for demographic information and primary and secondary outcomes. We included 89 studies for analysis. For the primary outcome, 31 (35%) studies assessed neurocognitive functions, and 27 (30%) used survival. For secondary outcomes, neurocognitive function was present in 20 (22%) studies, and survival was present in 10 (11%) studies. Twenty-six (29%) studies used both survival and neurocognitive function. Since the publication of the COSCA guidelines in 2018, there has been an increased focus on neurologic outcomes. Although survival outcomes are used frequently, we observed a trend toward fewer studies with ROSC as a primary outcome. There were no quality-of-life assessments, suggesting a need for more studies with patient-centered outcomes that can inform the guidelines for cardiac-arrest management.

Towards a ‘systems’ approach for viral challenge experiments in shrimp: Reporting guidelines for publication

AbstractThe success of contemporary disease management strategies in shrimp aquaculture, such as the ‘systems’ approach, is predicated on robust knowledge of the conditions and interactions between the host, pathogen and environment that promote disease. Pathogen challenge experiments (PCEs) are a power tool for investigating these conditions and interactions. However, absence of accurately reported experimental detail in published PCEs limits scientific transparency, reproducibility, and the potential for the research to make progressive advancements contributing to contemporary shrimp disease management strategies. This review identifies and discusses key factors relating to the host (shrimp), pathogen (virus), and environment that should be carefully considered during the design and publication of PCEs. We offer substantial evidence of their impact on viral disease outcomes, drawn from the existing body of literature, to supporting their consideration. The prevalence of reported experimental details for these factors across 186 viral PCEs in shrimp were evaluated. The review highlights a concerning paucity of experimental detail reported in published shrimp PCEs. We propose a checklist for the minimum reportable information in the publication of shrimp viral PCEs, hereafter referred to as the Shrimp PCE Reporting Guidelines (SPERG). The guidelines aim to enhance the transparency and standardisation of reporting in published PCEs, ensuring that key factors pertaining to the shrimp, pathogen, and environment are adequately considered and documented. Adoption of SPERG is envisaged to empower researchers, reviewers, and readers to assess the internal and external validity of PCEs, facilitating critical evaluation and improved utility of PCE findings for contemporary disease management.