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OBJECTIVES:This project involved development of a Health Background Study (HBS) Framework to support consideration of health impacts within municipalities' approval process for land use development. PARTICIPANTS:Peel Public Health and Toronto Public Health led the project with the participation of planners, urban designers, engineers, public health staff and development industry representatives. SETTING:Historical growth in the Region of Peel and suburban Toronto has resulted in extensive low-density development, creating car-dependent communities with disconnected streets and segregated land uses. INTERVENTION:The inclusion of an HBS in developers' applications to municipalities is one approach by which health-related expectations for the built environment can be established within the approval process. Development of the HBS Framework used the six core elements of the built environment with the strongest evidence for impact on health and was informed by analysis of the provincial and local policy contexts, practices of other municipalities and stakeholder interviews. The Framework's contents were refined according to feedback from multidisciplinary stakeholder workshops. OUTCOMES:The HBS Framework identifies minimum standards for built environment core elements that developers need to address in their applications. The Framework was created to be simple and instructive with applicability to a range of development locations and scales, and to various stages of the development approval process. Peel Public Health is leading several initiatives to support the use of the HBS as a part of the development application process. CONCLUSION:The HBS Framework is a tool that public health and planning can use to support the consideration of health impacts within municipalities' land use development processes.

The present study investigated nutritional programming in Atlantic salmon to improve utilisation of a vegetable-based diet. At first exogenous feeding, fry were fed either a marine-based diet (Diet Mstimulus, 80% fishmeal (FM)/4% fish oil (FO)) or a vegetable-based diet (Diet Vstimulus, 10% FM/0% FO) for 3 weeks. Subsequently, all fish were then fed under the same conditions with a commercial, marine-based, diet for 15 weeks and thereafter challenged with a second V diet (Diet Vchallenge, 10% FM/0% FO) for 6 weeks. Diploid and triploid siblings were run in parallel to examine ploidy effects. Growth performance, feed intake, nutrient utilisation and intestinal morphology were monitored. Fish initially given Diet Vstimulus (V-fish) showed 24 % higher growth rate and 23 % better feed efficiency compared with M-fish when later challenged with Diet Vchallenge. There was no difference in feed intake between nutritional histories, but increased nutrient retentions highlighted the improved utilisation of a V diet in V-fish. There were generally few significant effects of nutritional history or ploidy on enteritis scores in the distal intestine after the challenge phase as only V-triploids showed a significant increase (P<0·05) in total score. The data highlighted that the positive effects were most likely a result of nutritional programming and the ability to respond better when challenged later in life may be attributed to physiological and/or metabolic changes induced by the stimulus. This novel study showed the potential of nutritional programming to improve the use of plant raw material ingredients in feeds for Atlantic salmon.

OBJECTIFS :Notre projet impliquait l'élaboration d'un cadre d'étude de base sur la santé (ÉBS) qui permette de tenir compte des impacts sur la santé dans le processus d'approbation des plans d'aménagement du territoire des municipalités. PARTICIPANTS :Le Bureau de santé de la région de Peel et Santé publique Toronto ont dirigé le projet avec la participation de planificateurs, d'urbanistes, d'ingénieurs, de fonctionnaires en santé publique et de représentants du secteur de l'aménagement. LIEU :La croissance historique dans la Région de Peel et en banlieue de Toronto a entraîné un aménagement à faible densité généralisé, créant ainsi des communautés tributaires de l'automobile avec des rues sans issue et des utilisations compartimentées des terrains. INTERVENTION :L'inclusion d'une ÉBS dans les demandes que les promoteurs présentent aux municipalités est une approche permettant d'établir des attentes sanitaires pour le milieu bâti dans le processus d'approbation. L'élaboration du cadre d'ÉBS a utilisé les six éléments fondamentaux du milieu bâti pour lesquels il existe les indications les plus solides d'impacts sur la santé et s'est fondée sur l'analyse des contextes des politiques provinciales et locales, sur les pratiques d'autres municipalités et sur des entrevues avec les acteurs. Le contenu du cadre a été peaufiné à la lumière de la rétroaction d'ateliers multipartenaires et multidisciplinaires. RÉSULTATS :Le cadre d'ÉBS définit des normes minimales pour les éléments fondamentaux du milieu bâti que les promoteurs doivent aborder dans leurs demandes. Ce cadre se veut un outil simple et instructif qui peut s'appliquer à un éventail de lieux et d'échelles d'aménagement et aux diverses étapes du processus d'approbation des plans d'aménagement. Le Bureau de santé de la région de Peel dirige plusieurs initiatives qui appuient l'utilisation de l'ÉBS dans le processus de demande des plans d'aménagement. CONCLUSION :Le cadre d'ÉBS est un outil dont les fonctionnaires en santé publique et en planification peuvent se servir pour appuyer la prise en compte des impacts sur la santé dans les processus d'aménagement du territoire des municipalités.

This study examines three possible methods for improving the digestibility and bioavailability of zinc to rainbow trout (Oncorhynchus mikiss). The first method was to examine the availability of the zinc utilisation from commonly used protein sources; the second was to assess the efficacy of the upstream use of an enzyme treatment of the raw materials; the third was to assess the use of organically complexed mineral supplements as opposed to the inorganic salts widely used at present. The first section indicated that the zinc from the soyabean meal was the most available (49.4%). The zinc digestibilities of the animal based protein used in this current study were 15.1% for LT94 fish meal, 26.6% for the Provimi 66 white fishmeal and 15.8% for poultry meat meal. The zinc in the maize/corn gluten meal was 31.9% digestible and from the NuPro 26.1%. Gram for gram maize gluten meal supplied the least amount of zinc to the fish (3.66 mg per kg). Based on these results the diets for the subsequent supplementation trials were formulated. The liver, eye and caudal fin were identified biomarkers of a severe zinc deficiency. The second part of the study revealed a soybean product, treated by exogenous enzymes, had a higher phosphorus digestibility, (49.0%, vs. 36.6%) and zinc digestibility (30.7% vs. 7.9%) The treatment did not improve the protein digestibility (85%). The third part of the study showed the organic source proved more digestible than the inorganic, 37.4% and 26.9% respectively. The fish fed the organic source maintained a higher level of zinc in both the eye and caudal fin. The liver zinc levels were unaffected by both dietary level and zinc source. Analysis of the liver for a zinc dependant protein showed that under stress conditions only the organic supplemented fish were able to synthesis this protein. The analysis of the mRNA levels coding for this protein indicate the fish on both zinc forms up regulated the production of the mRNA to the same extent when stressed. Finally this study also examined the viability of using a stable isotope to identify different ‘preferences’ for one form of supplementation over the other in different tissues. This method illustrated a tissue dependant difference to how the fish attempted physiologically to compensate for zinc deficiency. The rate of turnover was fastest in the liver, then the caudal fin and then the eye, and also showed that when the diet was more deficient there was an increased ability for the tissues to take up the organic form.

Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic. We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent. Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group. ISRCTN 66726260.

AbstractObjectiveTo develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19).DesignProspective observational cohort study.SettingInternational Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium—ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020.ParticipantsAdults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction.Main outcome measureIn-hospital mortality.Results35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73).ConclusionsAn easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations.Study registrationISRCTN66726260

AbstractObjectiveTo characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C).DesignProspective observational cohort study with rapid data gathering and near real time analysis.Setting260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020).Participants651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2.Main outcome measuresAdmission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C.ResultsMedian age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 109/L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group.ConclusionsChildren and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive).Study registrationISRCTN66726260.

Background Our study examines if SARS-CoV-2 infections varied by vaccination status, if an individual had previously tested positive and by neighbourhood socioeconomic deprivation across the Delta and Omicron epidemic waves of SARS-CoV-2. Methods Population cohort study using electronic health records for 2.7 M residents in Cheshire and Merseyside, England (3rd June 2021 to 1st March 2022). Our outcome variable was registered positive test for SARS-CoV-2. Explanatory variables were vaccination status, previous registered positive test and neighbourhood socioeconomic deprivation. Cox regression models were used to analyse associations. Results Originally higher SARS-CoV-2 rates in the most socioeconomically deprived neighbourhoods changed to being higher in the least deprived neighbourhoods from the 1st September 2021, and were inconsistent during the Omicron wave. Individuals who were fully vaccinated (two doses) were associated with fewer registered positive tests (e.g., individuals engaged in testing between 1st September and 27th November 2021—Hazards Ratio (HR) = 0.48, 95% Confidence Intervals (CIs) = 0.47–0.50. Individuals with a previous registered positive test were also less likely to have a registered positive test (e.g., individuals engaged in testing between 1st September and 27th November 2021—HR = 0.16, 95% CIs = 0.15–0.18. However, the Omicron period saw smaller effect sizes for both vaccination status and previous registered positive test. Conclusions Changing patterns of SARS-CoV-2 infections during the Delta and Omicron waves reveals a dynamic pandemic that continues to affect diverse communities in sometimes unexpected ways.

Cardiovascular diseases are common in patients with chronic obstructive pulmonary disease (COPD). Clot formation and resolution secondary to systemic inflammation may be a part of the explanation. The aim was to determine whether biomarkers of clot formation (products of von Willebrand Factor formation and activation) and clot resolution (product of fibrin degeneration) during COPD exacerbation predicted major cardiovascular events (MACE). The cohort was based on clinical data and biobank plasma samples from a trial including patients admitted with an acute exacerbation of COPD (CORTICO-COP). Neo-epitope biomarkers of formation and the activation of von Willebrand factor (VWF-N and V-WFA, respectively) and cross-linked fibrin degradation (X-FIB) were assessed using ELISAs in EDTA plasma at the time of acute admission, and analyzed for time-to-first MACE within 36 months, using multivariable Cox proportional hazards models. In total, 299/318 participants had samples available for analysis. The risk of MACE for patients in the upper quartile of each biomarker versus the lower quartile was: X-FIB: HR 0.98 (95% CI 0.65–1.48), VWF-N: HR 1.56 (95% CI 1.07–2.27), and VWF-A: HR 0.78 (95% CI 0.52–1.16). Thus, in COPD patients with an acute exacerbation, VWF-N was associated with future MACE and warrants further studies in a larger population.

Detection of disease-associated variants in the BRCA1 and BRCA2 (BRCA1/2) genes allows for cancer prevention and early diagnosis in high-risk individuals. To identify pathogenic and likely pathogenic (P/LP) BRCA1/2 variants in an unselected research cohort, and to characterize the features associated with P/LP variants. This is a cross-sectional study of adult volunteers (n = 50 726) who underwent exome sequencing at a single health care system (Geisinger Health System, Danville, Pennsylvania) from January 1, 2014, to March 1, 2016. Participants are part of the DiscovEHR cohort and were identified through the Geisinger MyCode Community Health Initiative. They consented to a research protocol that included sequencing and return of actionable test results. Clinical data from electronic health records and clinical visits were correlated with variants. Comparisons were made between those with (cases) and those without (controls) P/LP variants in BRCA1/2. Prevalence of P/LP BRCA1/2 variants in cohort, proportion of variant carriers not previously ascertained through clinical testing, and personal and family history of relevant cancers among BRCA1/2 variant carriers and noncarriers. Of the 50 726 health system patients who underwent exome sequencing, 50 459 (99.5%) had no expected pathogenic BRCA1/2 variants and 267 (0.5%) were BRCA1/2 carriers. Of the 267 cases (148 [55.4%] were women and 119 [44.6%] were men with a mean [range] age of 58.9 [23-90] years), 183 (68.5%) received clinically confirmed results in their electronic health record. Among the 267 participants with P/LP BRCA1/2 variants, 219 (82.0%) had no prior clinical testing, 95 (35.6%) had BRCA1 variants, and 172 (64.4%) had BRCA2 variants. Syndromic cancer diagnoses were present in 11 (47.8%) of the 23 deceased BRCA1/2 carriers and in 56 (20.9%) of all 267 BRCA1/2 carriers. Among women, 31 (20.9%) of 148 variant carriers had a personal history of breast cancer, compared with 1554 (5.2%) of 29 880 noncarriers (odds ratio [OR], 5.95; 95% CI, 3.88-9.13; P < .001). Ovarian cancer history was present in 15 (10.1%) of 148 variant carriers and in 195 (0.6%) of 29 880 variant noncarriers (OR, 18.30; 95% CI, 10.48-31.4; P < .001). Among 89 BRCA1/2 carriers without prior testing but with comprehensive personal and family history data, 44 (49.4%) did not meet published guidelines for clinical testing. This study found that compared with previous clinical care, exome sequencing-based screening identified 5 times as many individuals with P/LP BRCA1/2 variants. These findings suggest that genomic screening may identify BRCA1/2-associated cancer risk that might otherwise remain undetected within health care systems and may provide opportunities to reduce morbidity and mortality in patients.