Dental health status, dentist visiting, and dental insurance of Asian immigrants in Canada.

OBJECTIVE: This study examined the dental care utilization and self-preserved dental health of Asian immigrants relative to non-immigrants in Canada. Factors associated with oral health-related disparities between Asian immigrants and other Canadians were further examined. METHODS: We analyzed 37,935 Canadian residents aged 12 years and older in the Canadian Community Health Survey 2012-2014 microdata file. Factors (e.g., demographics, socioeconomic status, lifestyles, dental insurance coverage, and year of immigration) associated with disparities in dental health (e.g., self-perceived teeth health, dental symptoms during past one month, and teeth removed due to decay in past one year) and service utilization (e.g., visiting dentist within the last three years, visiting dentist more than once per year) between Asian immigrants and other Canadians were examined using multi-variable logistic regression models. RESULTS: The frequency of dental care utilization was significantly lower in Asian immigrants than their non-immigrant counterparts. Asian immigrants had lower self-perceived dental health, were less likely to be aware of recent dental symptoms, and more likely to report tooth extractions due to tooth decay. Low education (OR = 0.42), male gender(OR = 1.51), low household income(OR = 1.60), non-diabetes(OR = 1.87), no dental insurance(OR = 0.24), short immigration length (OR = 1.75) may discourage Asian immigrants from dental care utilization. Additionally, a perceived lack of necessity to dentist-visiting was a crucial factor accounting for the disparities in dental care uptake between Asian immigrants and non-immigrants. CONCLUSION: Asian immigrants showed lower dental care utilization and oral health than native-born Canadians.

Effect of primary health care reforms in the province of Newfoundland and Labrador: Interrupted time-series analysis.

OBJECTIVE: To examine the effects of primary health care (PHC) reforms in the Canadian province of Newfoundland and Labrador on ambulatory care-sensitive (ACS) hospitalization rates and mortality. DESIGN: Interrupted time-series analysis of administrative data. SETTING: All communities in the province of Newfoundland and Labrador were divided into 3 groups: rural reform (n = 69 143), rural nonreform (n = 228 914), and urban nonreform (n = 197 012). No urban communities introduced PHC reforms. PARTICIPANTS: All residents of the province who held a valid health card and did not change their address during the 2001-2009 study period were included. Individuals were assigned to 1 of the 3 study groups based on community of residence. MAIN OUTCOME MEASURES: Hospitalization rates for ACS conditions, hospitalization rates for control conditions, and ACS-related mortality were compared using interrupted time-series models. RESULTS: Results are reported as rate ratio or odds ratio (OR) (95% CI). In rural reform and rural nonreform communities, there was a decreasing trend in ACS hospitalization rates that preceded reforms (rate ratio of 0.97 [0.94-1.00]) and rate ratio of 0.98 [0.96-1.00], respectively) but no change following reforms. There were no significant changes in the urban group. In all 3 groups, there was a significant increasing trend in ACS-related mortality before reforms (OR of 1.09 [1.02-1.15], OR of 1.10 [1.06-1.13], and OR of 1.09 [1.05-1.14] for rural reform, rural nonreform, and urban communities, respectively), which was reversed after the introduction of reforms (P < .01). CONCLUSION: Primary health care reforms in Newfoundland and Labrador had no observed effect on ACS hospitalization rates, but a potential effect might have been masked by a decreasing trend that preceded the introduction of reforms. The increase in mortality rates that was reversed after the introduction of reforms cannot be attributed to the reforms because it occurred in all studied populations including those that did not introduce reforms.

Antineoplastic Agents. 585. Isolation of Bridelia ferruginea Anticancer Podophyllotoxins and Synthesis of 4-Aza-podophyllotoxin Structural Modifications.

Cytotoxic constituents of the terrestrial plant Bridelia ferruginea were isolated using bioactivity-guided fractionation, which revealed the presence of the previously known deoxypodophyllotoxin (1), isopicrodeoxypodophyllotoxin (2), ß-peltatin (3), ß-peltatin-5-O-ß-D-glucopyranoside (3a), and the indole neoechinulin (4). As an extension of previous podophyllotoxin research, SAR studies were undertaken focused on 4-aza-podophyllotoxin structural modifications. A number of such derivatives were synthesized following modifications to the A and E rings. Such structural modifications with alkyl and 4-fluorobenzyl substituents at the 4-aza position provided the most potent cancer cell growth inhibitory activity (GI50 0.1 to <0.03 µg/mL) against a panel of six human cancer cell lines and one murine cancer cell line. Several compounds corresponding to 4'-demethylated modifications were also synthesized and found to be significantly less potent.

Isolation and Structure of Cancer Cell Growth Inhibitory Tetracyclic Triterpenoids from the Zimbabwean Monadenium lugardae.

The Zimbabwean medicinal plant Monadenium lugardae was evaluated as a potential source of new anticancer constituents. Four new tetracyclic triterpene (1-4) were isolated, accompanied by four previously known triterpenes (5-8). Against a panel of human tumor cell lines, lugardstatins 1 (1) and 2 (2) had good cancer cell growth inhibitory activity. All of the triterpene structures (1-8) were established by 1D and 2D NMR spectrometric and HR mass spectrometric analysis.

The Cephalostatins. 23. Conversion of Hecogenin to a Steroidal 1,6-Dioxaspiro[5.5]nonane Analogue for Cephalostatin 11.

Cephalostatin 1 (1) has proved to be a remarkably potent cancer cell growth inhibitor. Since this steroidal alkaloid constituent of the marine worm Cephalodiscus gilchristi possesses a complex structure, providing preclinical supplies by total synthesis continues to be challenging. Therefore, syntheses of less complex structural modifications of this important pyrazine have also received substantial attention. Herein are summarized the synthesis of [5.5]spiroketal 5, a simplified right-side steroidal unit of 1, in seven steps from hecogenin acetate (11) with an overall yield of 4.6%. Consistent with other SAR studies, such reduction in structural complexity compared to 1 led to loss of cancer cell growth inhibitory activity against the P388 lymphocytic leukemia cell line.

Racial and sociodemographic distribution of colorectal cancer screening in Canada: A cross-sectional study.

OBJECTIVES: To assess the racial and sociodemographic distribution of colorectal cancer (CRC) screening uptake in Canada, identify disparities, and evaluate the potential predictors and barriers to CRC screening. METHODS: Data from the 2017 cycle of the Canadian Community Health Survey (CCHS) were analyzed, focusing on individuals aged 50-74 years. CRC screening participation rates were evaluated at both national and provincial levels and across various sociodemographic characteristics. Multivariable logistic regression models were employed to identify predictors and barriers to CRC screening. RESULTS: Of the 56,950 respondents to the 2017 CCHS, 41.7% (n = 23,727) were between 50 and 74 years of age. The overall CRC screening participation rate was 59.8%, with provinces like Alberta and Manitoba achieving rates of 65.7% and 66.5%, respectively. Significant disparities were observed across socioeconomic, geographical, and racial or ethnic groups. Notably, older adults [AOR 2.41, 95% CI 2.06‒2.83], higher income earners [AOR 1.99, 95% CI 1.77‒2.24], and non-smokers [AOR 1.76, 95% CI 1.55‒2.0] had higher odds of screening, while immigrants and minority ethnic groups, especially South-East Asians [AOR 0.48, 95% CI 0.29‒0.78] and South Asians [AOR 0.65, 95% CI 0.44‒0.95], had lower odds of being up to date with CRC screening. A significant portion of unscreened individuals cited their healthcare provider's perception of the test as unnecessary. CONCLUSION: While there is promising progress in CRC screening participation rates across Canada, significant disparities persist. Addressing these disparities is crucial for public health. Efforts should focus on enhancing public awareness, facilitating accessibility, and ensuring cultural appropriateness of CRC screening initiatives.

RéSUMé: OBJECTIFS: Évaluer la distribution raciale et sociodémographique de la participation au dépistage du cancer colorectal (CCR) au Canada, identifier les disparités et évaluer les potentiels prédicteurs et obstacles au dépistage du CCR. MéTHODES: Les données du cycle 2017 de l'Enquête sur la santé dans les collectivités canadiennes (ESCC) ont été analysées, en se concentrant sur les individus âgés de 50 à 74 ans. Les taux de participation au dépistage du CCR ont été évalués à la fois au niveau national et provincial et selon diverses caractéristiques sociodémographiques. Des modèles de régression logistique multivariée ont été utilisés pour identifier les prédicteurs et les obstacles au dépistage du CCR. RéSULTATS: Sur les 56 950 répondants à l'ESCC 2017, 41,7% (n = 23 727) étaient âgés de 50 à 74 ans. Le taux global de participation au dépistage du CCR était de 59,8%, des provinces comme l'Alberta et le Manitoba atteignant des taux de 65,7% et 66,5% respectivement. Des disparités significatives ont été observées selon les groupes socioéconomiques, géographiques et raciaux ou ethniques. Notamment, les personnes âgées [AOR 2,41, IC 95% 2,06‒2,83], les personnes à revenu élevé [AOR 1,99 IC 95% 1,77‒2,24] et les non-fumeurs [AOR 1,76, IC 95% 1,55‒2,0] avaient des chances plus élevées de dépistage, tandis que les immigrants et les groupes ethniques minoritaires, en particulier les Asiatiques du Sud-Est [AOR 0,48, IC 95% 0,29‒0,78] et les Asiatiques du Sud [AOR 0,65, IC 95% 0,44‒0,95] avaient moins de chances d'être à jour avec le dépistage du CCR. Une part significative des individus non dépistés a cité la perception de leur prestataire de soins de santé selon laquelle le test était inutile. CONCLUSION: Bien qu'il y ait une progression prometteuse des taux de participation au dépistage du CCR au Canada, des disparités significatives persistent. Il est crucial pour la santé publique de s'attaquer à ces disparités. Les efforts devraient se concentrer sur l'amélioration de la sensibilisation du public, la facilitation de l'accessibilité et la garantie de l'adéquation culturelle des initiatives de dépistage du CCR.

Isolation and structures of axistatins 1-3 from the Republic of Palau marine sponge Agelas axifera Hentschel .

An investigation begun in 1979 directed at the Republic of Palau marine sponge Agelas axifera Hentschel for cancer cell growth inhibitory constituents subsequently led to the isolation of three new pyrimidine diterpenes designated axistatins 1 (1), 2 (2), and 3 (3), together with the previously reported formamides 4, 5, and agelasine F (6). The structures were elucidated by analysis of 2D-NMR spectra and by HRMS. All of the isolated compounds were found to be moderate inhibitors of cancer cell growth. Axistatins 1-3 (1-3), formamide 4, and agelasine F (6) also exhibited antimicrobial activity.

Dental Insurance Coverage, Dentist Visiting, and Oral Health Status among Asian Immigrant Women of Childbearing Age in Canada: A Comparative Study.

OBJECTIVES: This study examined the dental insurance coverage, dentist visits, self-perceived oral health status, and dental problems among Asian immigrant women of childbearing age in contrast to Canadian women of childbearing age and non-Asian immigrant women of childbearing age. Potential barriers to dental care services among Asian immigrant women were explored. METHODS: This analysis utilized data from the combined Canadian Community Health Survey from 2011 to 2014. The analytical sample consisted of 5737 females whose age was between 20 and 39 years. Multivariable logistic regression models assessed immigrant status and other factors in relation to the indicators of dental health (i.e., dental visit, self-perceived oral health, acute teeth issue, and teeth removed due to decay). RESULTS: Amongst Asian women immigrants of childbearing age, there was a significantly lower frequency of dentist visits compared to non-immigrant counterparts (OR = 0.53; 95% CI: 0.37-0.76). The most commonly reported reason for not seeking dental care in the last three years was that the "respondent did not think it was necessary". Relative to Canadian born women of same age bracket, Asian women of childbearing age reported fewer acute teeth issues (OR = 0.67; 95% CI: 0.49-0.91) and had a greater risk of tooth extracted due to tooth decay (OR = 3.31; 95% CI: 1.64-6.68). Furthermore, for Asian women immigrants, their major barriers to dental care included low household income (≤$39,999 vs. $40,000-$79,999 OR = 0.26) and a lack of dental insurance (no vs. yes OR = 0.33). CONCLUSIONS: Asian immigrant women showed lower utilization of dental services than non-immigrant women. A perceived lack of necessity, lower household income, and dental insurance coverage were major barriers to professional dental usage for most Asian immigrants of childbearing age.

The cephalostatins. 22. synthesis of bis-steroidal pyrazine pyrones (1).

Cephalostatin 1 (1), a remarkably strong cancer cell growth inhibitory trisdecacyclic, bis-steroidal pyrazine isolated from the marine tube worm Cephalodiscus gilchristi, continues to be an important target for practical total syntheses and a model for the discovery of less complex structural modifications with promising antineoplastic activity. In the present study, the cephalostatin E and F rings were greatly simplified by replacement at C-17 with an α-pyrone (in 12), typical of the steroidal bufodienolides, and by a dihydro-γ-pyrone (in 16). The synthesis of pyrazine 12 from 5α-dihydrotestosterone (nine steps, 8% overall yield) provided the first route to a bis-bufadienolide pyrazine. Dihydro-γ-pyrone 16 was synthesized in eight steps from ketone 13. While only insignificant cancer cell growth inhibitory activity was found for pyrones 12 and 16, the results provided further support for the necessity of more closely approximating the natural D-F ring system of cephalostatin 1 in order to obtain potent antineoplastic activity.

Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs.

Toward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line. Of the diiodo series, 12a was also found to markedly inhibit growth of pediatric neuroblastoma, and monoiodocombstatin 9a strongly inhibited HUVEC growth. Overall, the strongest activity was found against the breast, CNS, leukemia, lung, and prostate cancer cell lines and the least activity against the pancreas and colon lines. Parallel biological investigations of tubulin interaction, antiangiogenesis, and antimicrobial effects were also conducted.

A Quality Improvement Emergency Department Surge Management Platform (SurgeCon): Protocol for a Stepped Wedge Cluster Randomized Trial.

BACKGROUND: Despite many efforts, long wait times and overcrowding in emergency departments (EDs) have remained a significant health service issue in Canada. For several years, Canada has had one of the longest wait times among the Organisation for Economic Co-operation and Development countries. From a patient's perspective, this challenge has been described as "patients wait in pain or discomfort for hours before being seen at EDs." To overcome the challenge of increased wait times, we developed an innovative ED management platform called SurgeCon that was designed based on continuous quality improvement principles to maintain patient flow and mitigate the impact of patient surge on ED efficiency. The SurgeCon quality improvement intervention includes a protocol-driven software platform, restructures ED organization and workflow, and aims to establish a more patient-centric environment. We piloted SurgeCon at an ED in Carbonear, Newfoundland and Labrador, and found that there was a 32% reduction in ED wait times. OBJECTIVE: The primary objective of this trial is to determine the effects of SurgeCon on ED performance by assessing its impact on length of stay, the time to a physician's initial assessment, and the number of patients leaving the ED without being seen by a physician. The secondary objectives of this study are to evaluate SurgeCon's effects on patient satisfaction and patient-reported experiences with ED wait times and its ability to create better-value care by reducing the per-patient cost of delivering ED services. METHODS: The implementation of the intervention will be assessed using a comparative effectiveness-implementation hybrid design. This type of hybrid design is known to shorten the amount of time associated with transitioning interventions from being the focus of research to being used for practice and health care services. All EDs with 24/7 on-site physician support (category A hospitals) will be enrolled in a 31-month, pragmatic, stepped wedge cluster randomized trial. All clusters (hospitals) will start with a baseline period of usual care and will be randomized to determine the order and timing of transitioning to intervention care until all hospitals are using the intervention to manage and operationalize their EDs. RESULTS: Data collection for this study is continuing. As of February 2022, a total of 570 randomly selected patients have participated in telephone interviews concerning patient-reported experiences and patient satisfaction with ED wait times. The first of the 4 EDs was randomly selected, and it is currently using SurgeCon's eHealth platform and applying efficiency principles that have been learned through training since September 2021. The second randomly selected site will begin intervention implementation in winter 2022. CONCLUSIONS: By assessing the impact of SurgeCon on ED services, we hope to be able to improve wait times and create better-value ED care in this health care context. TRIAL REGISTRATION: ClinicalTrials.gov NCT04789902; https://clinicaltrials.gov/ct2/show/NCT04789902. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30454.

The cephalostatins. 21. Synthesis of bis-steroidal pyrazine rhamnosides (1).

The synthesis of bis-steroidal pyrazines derived from 3-oxo-11,21-dihydroxypregna-4,17(20)-diene (4) and glycosylation of a D-ring side chain with α-L-rhamnose have been summarized. Rearrangement of steroidal pyrazine 10 to 14 was found to occur with boron triflouride etherate. Glycosylation of pyrazine 10 using 2,3,4-tri-O-acetyl-α-L-rhamnose iodide led to 1,2-orthoester-α-L-rhamnose pyrazine 17b. By use of a persilylated α-L-rhamnose iodide as donor, formation of the orthoester was avoided. Bis-steroidal pyrazine 10 and rhamnosides 17b and 21c were found to significantly inhibit cancer cell growth in a murine and human cancer cell line panel. Pyrazine 9 inhibited growth of the nosocomial pathogen Enterococcus faecalis.

Antineoplastic agents. 590. X-ray crystal structure of dolastatin 16 and syntheses of the dolamethylleuine and dolaphenvaline units.

Three advances necessary to bring dolastatin 16 (1) into full-scale preclinical development as an anticancer drug have been accomplished. The X-ray crystal structure of dolastatin 16 has been solved, which allowed stereoselective syntheses of its two new amino acid units, dolamethylleuine (Dml) and dolaphenvaline (Dpv), to be completed. The X-ray crystal structures of synthetic Z-Dml and TFA-Dpv have also been completed.

Pediatric high users of Canadian hospitals and emergency departments.

INTRODUCTION: Few studies have examined the most frequent pediatric users of hospital services. Our objective was to determine the clinical diagnoses, demographic characteristics, and medical severity of high-use pediatric patients in Canada. METHODS: We conducted a retrospective analysis of patients <18 years of age who either were admitted to hospital or visited an emergency department (ED) using the Canadian Institute for Health Information's (CIHI) Dynamic Cohort of Complex, High System Users. The analysis of hospital admission data excluded Quebec and Manitoba. ED data was only available for Alberta and Ontario. RESULTS: 121 104 patients were identified as the most frequent hospital users and 459 998 patients as the most frequent ED users. High users were more likely to reside in a rural community, to be in a lower income quintile, and face more deprivation. The most frequent conditions for hospitalization for high use patients were disorders related to length of prematurity and fetal growth, respiratory and cardiovascular disorders specific to the perinatal period, and haemorrhagic and haematological disorders of fetus and newborn. For the most frequent ED users, the most common clinical diagnoses were acute upper respiratory infections, injuries to the head, and diseases of the middle ear and mastoid. CONCLUSION: Pediatric high users by frequency of hospital and ED services are a distinct population. Better understanding their characteristics will allow for more appropriate planning of children's health services and help identify areas for effective preventive or quality improvement initiatives.

Association of chronic pain with comorbidities and health care utilization: a retrospective cohort study using health administrative data.

ABSTRACT: Health administrative data provide a potentially robust information source regarding the substantial burden chronic pain exerts on individuals and the health care system. This study aimed to use health administrative data to estimate comorbidity prevalence and annual health care utilization associated with chronic pain in Newfoundland and Labrador, Canada. Applying the validated Chronic Pain Algorithm to provincial Fee-for-Service Physician Claims File data (1999-2009) established the Chronic Pain (n = 184,580) and No Chronic Pain (n = 320,113) comparator groups. Applying the Canadian Chronic Disease Surveillance System coding algorithms to Claims File and Provincial Discharge Abstract Data (1999-2009) determined the prevalence of 16 comorbidities. The 2009/2010 risk and person-year rate of physician and diagnostic imaging visits and hospital admissions were calculated and adjusted using the robust Poisson model with log link function (risks) and negative binomial model (rates). Results indicated a significantly higher prevalence of all comorbidities and up to 4 times the odds of multimorbidity in the Chronic Pain Group (P-value < 0.001). Chronic Pain Group members accounted for 58.8% of all physician visits, 57.6% of all diagnostic imaging visits, and 54.2% of all hospital admissions in 2009/2010, but only 12% to 16% of these were for pain-related conditions as per recorded diagnostic codes. The Chronic Pain Group had significantly higher rates of physician visits and high-cost hospital admission/diagnostic imaging visits (P-value < 0.001) when adjusted for demographics and comorbidities. Observations made using this methodology supported that people identified as having chronic pain have higher prevalence of comorbidities and use significantly more publicly funded health services.

Identifying cases of chronic pain using health administrative data: A validation study.

BACKGROUND: Most prevalence estimates of chronic pain are derived from surveys and vary widely, both globally (2%-54%) and in Canada (6.5%-44%). Health administrative data are increasingly used for chronic disease surveillance, but their validity as a source to ascertain chronic pain cases is understudied. AIM: The aim of this study was to derive and validate an algorithm to identify cases of chronic pain as a single chronic disease using provincial health administrative data. METHODS: A reference standard was developed and applied to the electronic medical records data of a Newfoundland and Labrador general population sample participating in the Canadian Primary Care Sentinel Surveillance Network. Chronic pain algorithms were created from the administrative data of patient populations with chronic pain, and their classification performance was compared to that of the reference standard via statistical tests of selection accuracy. RESULTS: The most performant algorithm for chronic pain case ascertainment from the Medical Care Plan Fee-for-Service Physicians Claims File was one anesthesiology encounter ever recording a chronic pain clinic procedure code OR five physician encounter dates recording any pain-related diagnostic code in 5 years with more than 183 days separating at least two encounters. The algorithm demonstrated 0.703 (95% confidence interval [CI], 0.685-0.722) sensitivity, 0.668 (95% CI, 0.657-0.678) specificity, and 0.408 (95% CI, 0.393-0.423) positive predictive value. The chronic pain algorithm selected 37.6% of a Newfoundland and Labrador provincial cohort. CONCLUSIONS: A health administrative data algorithm was derived and validated to identify chronic pain cases and estimate disease burden in residents attending fee-for-service physician encounters in Newfoundland and Labrador.

Contexte: La plupart des estimations de prévalence de la douleur chronique sont tirées d'enquêtes et varient considérablement, à la fois dans le monde (2 % -54 %) et au Canada (6,5 % - 44 %). Les données administratives sur la santé utilisées pour la surveillance des maladies chroniques, mais leur validité comme source pour déterminer les cas de douleur chronique est sous-étudiée.Objectif: Le but de cette étude était de dériver et de valider un algorithme pour répertorier les cas de douleur chronique comme une seule maladie chronique en utilisant les données administratives provinciales sur la santé.Méthodes: Une norme de référence a été élaborée et appliquée aux données des dossiers médicaux électroniques d'un échantillon de la population générale de Terre-Neuve-et-Labrador participant au Réseau canadien de surveillance sentinelle en soins primaires. Des algorithmes de douleur chronique ont été créés à partir des données administratives de populations de patients souffrant de douleur chronique et leur rendement en matière de classification a été comparé à celui de la norme de référence par le biais de tests statistiques sur la précision de sélection.Résultats: L'algorithme le plus performant pour la détermination des cas de douleur chronique à partir du Registre des paiements des soins médicaux rémunérés à l'acte était une seule consultation en anesthésiologie au cours de laquelle un code de procédure d'intervention clinique en matière de douleur chronique était enregistré OU cinq consultations médicales en cinq ans au cours desquelles était enregistré tout code de diagnostic lié à la douleur, avec une période de plus de 183 jours entre au moins deux consultations.L'algorithme a démontré une sensibilité de 0,703 (intervalle de confiance [IC] à 95 %, 0,685 à 0,722), une spécificité de 0,668 (IC 95 %, 0,657-0,678) et une valeur prédictive positive de 0,408 (IC 95 %, 0,393-0,423). L'algorithme de la douleur chronique a sélectionné 37,6 % d'une cohorte provinciale de Terre-Neuve-et-Labrador.Conclusions: Un algorithme de données administratives sur la santé a été dérivé et validé pour répertorier les cas de douleur et estimer le fardeau de la maladie chez les résidents ayant consulté un médecin rémunéré à l'acte à Terre-Neuve et Labrador.

Acute diabetes complications across transition from pediatric to adult care in Ontario and Newfoundland and Labrador: a population-based cohort study.

BACKGROUND: Transition to adult diabetes care is a high-risk period for acute complications, yet the optimal transition care model is unknown. To gain insight into the impact on health outcomes of system-level transition processes that reflect resourcing differences, we examined acute complications in youth with diabetes across transition in 2 Canadian provinces with different transition care models. METHODS: We used linked provincial health administrative data for Ontario and Newfoundland and Labrador to create 2 parallel cohorts of youth with diabetes diagnosed before age 15 years who turned 17 between 2006 and 2011. Participants were followed until 2015 (maximum age 21 yr). We described rates of and proportion of participants with at least 1 diabetes-related hospital admission at age 15-17 years and 18-20 years, standardized according to material deprivation based on the 2006 Canadian Marginalization Index. We compared diabetes-related admissions at age 15-17 years and 18-20 years in the Ontario cohort. RESULTS: The cohorts consisted of 2525 youth in Ontario and 93 in Newfoundland and Labrador. In Newfoundland and Labrador, 39 participants (42.0%) were in the lowest socioeconomic quintile, versus 326 (12.9%) in Ontario. The standardized rate of diabetes-related hospital admissions per 100 person-years was 13.5 (95% confidence interval [CI] 12.6-14.4) at age 15-17 years and 14.4 (95% CI 13.5-15.3) at age 18-20 years in Ontario, and 11.4 (95% CI 7.0-15.8) at age 15-17 years and 10.5 (95% CI 6.4-14.6) at age 18-20 years in Newfoundland and Labrador. In Ontario, there was no association between the rate (adjusted rate ratio 1.10, 95% CI 0.94-1.28) or occurrence (adjusted odds ratio 1.03, 95% CI 0.91-1.17) of diabetes-related admissions across transition. INTERPRETATION: Although posttransition care is delivered differently in the 2 provinces, rates of adverse events across transition were stable in both. Coordinated support during transition is needed to help mitigate adverse events for young adults in both provinces. Delivery of other health care and social services, including primary care, may be influencing the risk of adverse events after transition to adult care.

Antineoplastic agents. 578. Synthesis of stilstatins 1 and 2 and their water-soluble prodrugs.

Efficient syntheses of 3,4-methylenedioxy-4',5-dimethoxy-2',3'-dihydroxy-Z-stilbene (stilstatin 1, 2), 3,4,4'-trimethoxy-2',3',5-trihydroxy-Z-stilbene (stilstatin 2, 5), and respective phosphate prodrugs have been summarized. Both 2 and 5 were accessed via a convergent step synthesis using phosphonium bromides 6 and 21 in Wittig reactions with 2,3-bis(tert-butyldimethylsilyloxy)-4'-methoxybenzaldehyde 14. Deprotection of silyl ethers 15 and 26 with TBAF furnished 2 and 5, respectively. Phosphorylation of 2 and 5 afforded the phosphoric acid intermediates 17 and 28 for prodrug development. These phosphoric acid precursors were employed in parallel series of reactions to produce a selection of metal cation prodrug candidates. The biological activities of stilstatins 1 (2) and 2 (5) and their respective prodrugs were evaluated against a panel of one murine (P388) and six human cancer cell lines. Compared to combretastatin A-2 (1), stilstatin 1 (2) has an additional vicinal hydroxy group on the B ring, the presence of which was detrimental to the cancer cell line potency; in vivo, however, compound 2 would be predicted to have greater anticancer activity resulting from the o-quinone mechanism of action analogous to that of combretastatin A-1 (4). The substitution of a hydroxy group for a methoxy group on the A ring of combretastatin A-1 (4), resulting in stilstatin 2 (5), gave rise to a modest level of inhibition consistent with that found for 4 against cancer cell lines.

Antineoplastic agents. 571. Total synthesis of bacillistatin 2.

The first total synthesis of bacillistain 2 (2) has been achieved in 24 steps and 22.9% overall yield, providing a quite efficient route with maximal convergence. Notable features of this approach include two successful applications of the Mitsunobu reaction during respective assemblies of key intermediates 22 and 27, successful employment of 2-methyl-6-nitrobenzoic anhydride (MNBA) in the formation by lactonization of a macrocyclic (36-membered) ring, and very flexible access to structural modifications of the bacillistatin-type cyclodepsipeptides.

Antineoplastic agents. 579. Synthesis and cancer cell growth evaluation of E-stilstatin 3: a resveratrol structural modification.

As an extension of our earlier structure/activity investigation of resveratrol (1a) cancer cell growth inhibitory activity compared to the structurally related stilbene combretastatin series (e.g., 2a), an efficient synthesis of E-stilstatin 3 (3a) and its phosphate prodrug 3b was completed. The trans-stilbene 3a was obtained using a convergent synthesis employing a Wittig reaction with phosphonium bromide 9 as the key reaction step. Deprotection of the Z-silyl ether 13 gave E-stilstatin 3 (3a) as the exclusive product. The structure and stereochemistry of 3a was confirmed by X-ray crystal structure determination.