Coordination-cage binding and catalysed hydrolysis of organophosphorus chemical warfare agent simulants.

The use of organophosphorus chemical warfare agents still remains an ongoing global threat. Here we investigate the binding of small-molecule organic guests including phosphate esters, sulfonate esters, carbonate esters and a sulfite ester - some of which act as simulants for organophosphorus chemical warfare agents - in the cavity of a water-soluble coordination cage. For several of these guest species, binding constants in the range 102 to 103 M-1 were determined in water/DMSO (98 : 2 v/v) solution, through a combination of fluorescence and 1H NMR spectroscopy, and subsequent fitting of titration data to a 1 : 1 binding isotherm model. For three cage/guest complexes crystallographic structure determinations were possible: in two cases (with guests phenyl methanesulfonate and phenyl propyl carbonate) the guest lies inside the cavity, forming a range of CH⋯O hydrogen-bonding interactions with the cage interior surface involving CH groups on the cationic cage surface that act as H-bond donors and O atoms on the guests that act as H-bond acceptors. In a third case, with the guest 4-nitrophenyl-methanesulfonate, the guest lies in the spaces outside a cage cavity between cages and forms weak CH⋯O interactions with the cage exterior surface: the cavity is occupied by a network of H-bonded water molecules, though this guest does show cavity binding in solution. For the isomeric guests 4-nitrophenyl-methanesulfonate and 4-nitrophenyl methyl sulfite, hydrolysis in water/DMSO (98 : 2 v/v) could be monitored colorimetrically via appearance of the 4-nitrophenolate anion; both showed accelerated hydrolysis rates in the presence of the host cage with second-order rate constants for the catalysed reactions in the range 10-3 to 10-2 M-1 s-1 at pH 9. The typical rate dependence on external pH and the increased reaction rates when chloride ions are present (which can bind inside the cavity and displace other cavity-bound guests) imply that the catalysed reaction actually occurs at the external surface of the cage rather than inside the cavity.

Wait times and breast cancer survival: a population-based retrospective cohort study using CanIMPACT data.

PURPOSE: The time from breast cancer surgery to chemotherapy has been shown to affect survival outcomes; however, the effect of time from first breast cancer-related healthcare contact to first cancer specialist consultation, or the time from first breast cancer-related healthcare contact to adjuvant chemotherapy on survival has not been well explored. We aimed to determine whether various wait times along the breast cancer treatment pathway (contact-to-consultation, contact-to-chemotherapy, surgery-to-chemotherapy) were associated with overall survival in women within the Canadian province of Ontario. METHODS: We performed a population-based retrospective cohort study of women diagnosed with stage I-III breast cancer in Ontario between 2007 and 2011 who received surgery and adjuvant chemotherapy. This was the Ontario cohort of a larger, nationwide study (the Canadian Team to improve Community-Based Cancer Care along the Continuum - CanIMPACT). We used Cox-proportional hazards regression to determine the association between the contact-to-consultation, contact-to-chemotherapy, and surgery-to-chemotherapy intervals and overall survival while adjusting for cancer stage, age, comorbidity, neighborhood income, immigration status, surgery type, and method of cancer detection. RESULTS: Among 12,782 breast cancer patients, longer surgery-to-chemotherapy intervals (HR 1.13, 95% CI 1.03-1.18 per 30-day increase), but not the contact-to-consultation (HR 0.979, 95% CI 0.95-1.01 per 30-day increase), nor the more comprehensive contact-to-chemotherapy intervals (HR 1.00, 95% CI 0.98-1.02 per 30-day increase) were associated with decreased survival in our adjusted analyses. CONCLUSION: Our findings emphasize the prognostic importance of a shorter surgery-to-chemotherapy interval, whereas the contact-to-consultation and contact-to-chemotherapy intervals have less impact on survival outcomes.

Celiac Disease and Inflammatory Bowel Disease Are Associated With Increased Risk of Eating Disorders: An Ontario Health Administrative Database Study.

INTRODUCTION: Previous national registry studies have reported an increased risk of eating disorders in immune-mediated conditions (inflammatory bowel disease and celiac disease). Our objective was to examine the association between immune-mediated gastrointestinal (GI) diseases and incident eating disorders in Ontario. METHODS: This was a retrospective matched cohort study of individuals <50 years of age with a diagnosis of an immune-mediated GI disease between 2002 and 2020 ("cases"). Those with a pre-existing eating disorder were excluded. Cases (n = 83,920) were matched with controls (n = 167,776) based on birth year, sex, and region of residence. Incidence rate ratio and hazard ratio were estimated using Poisson regression model and adjusted Cox proportional models, respectively. RESULTS: Over the follow-up period (up to January 31, 2022), 161 cases and 160 controls were identified with eating disorders. The overall incidence rate ratio (95% confidence interval, P -value) of eating disorders in immune-mediated GI disease was 1.99 (1.6-2.5, P < 0.001). The adjusted hazard ratio for eating disorder in cases with immune-mediated GI diseases was 1.98 (1.6-2.5, P < 0.001). In the pediatric group of incident cases (≤18 years of age), overall adjusted hazard ratio was 2.62 (1.9-3.7, P < 0.001) compared with 1.56 (1.02-2.4, P = 0.041) for adults (>18 years of age). The largest hazard ratio of 4.11 (1.6-10.3, P = 0.003) was observed for pediatric incident cases of ulcerative colitis. DISCUSSION: Inflammatory bowel disease and celiac disease are associated with the development of eating disorders. The magnitude of the association was stronger in the pediatric age group, underscoring the need for early screening and detection.

Breast (female), colorectal, and lung cancer survival in people with intellectual or developmental disabilities: A population-based retrospective cohort study.

OBJECTIVES: Cancer is a leading cause of death among people living with intellectual or developmental disabilities (IDD). There is little empirical evidence documenting survival or comparing outcomes to those without IDD. This study investigated the association between IDD and cancer survival among adults with breast (female), colorectal, or lung cancer. METHODS: A population-based retrospective cohort study was conducted in Ontario, Canada, with routinely collected data. Patients with breast, colorectal, or lung cancer were included (2007‒2019). IDD status before cancer was determined using an established administrative data algorithm. The outcomes of interest included death from any cause and death from cancer. Cox proportional hazards models and competing events analyses using multivariable cause-specific hazards regression were completed. Analyses were stratified by cancer type. Interactions with age, sex, and stage at diagnosis, as well as sensitivity analyses, were completed. RESULTS: The final cohorts included 123,695 breast, 98,809 colorectal, and 116,232 lung cancer patients. Individuals with IDD experienced significantly worse survival than those without IDD. The adjusted hazard ratios of all-cause death were 2.74 (95% CI 2.41‒3.12), 2.42 (95% CI 2.18‒2.68), and 1.49 (95% CI 1.34‒1.66) times higher for breast, colorectal, and lung cancer patients with IDD relative to those without. These findings were consistent for cancer-specific deaths. With few exceptions, worse survival for people with IDD persisted regardless of stage at diagnosis. CONCLUSION: People with IDD experienced worse cancer survival than those without IDD. Identifying and intervening on the factors and structures responsible for survival disparities is imperative.

RéSUMé: OBJECTIFS: Le cancer est l'une des principales causes de mortalité chez les personnes vivant avec des déficiences intellectuelles ou des troubles du développement (DI/TD). Il y a peu de preuves empiriques décrivant la survie de ces personnes lorsqu'elles sont atteintes d'un cancer ou comparant leurs résultats à ceux des personnes sans DI/TD. Notre étude porte sur l'association entre les DI/TD et la survie au cancer chez les adultes atteints de cancer du sein (femmes), du colorectum ou du poumon. MéTHODE: Une étude de cohorte rétrospective populationnelle a été menée en Ontario, au Canada, à l'aide de données recueillies systématiquement. Nous avons inclus les patientes et les patients atteints de cancer du sein, du colorectum ou du poumon (2007‒2019). Nous avons identifié la présence des DI/TD avant le cancer à l'aide d'un algorithme de traitement de données administratives reconnu. Les résultats d'intérêt étaient les décès de toutes causes et les décès dus au cancer. Nous avons appliqué des modèles des risques proportionnels de Cox et des analyses des événements concurrents en utilisant la régression multivariée des risques par cause. Nos analyses ont été stratifiées selon le type de cancer. Nous avons tenu compte des interactions avec l'âge, le sexe et le stade au diagnostic et effectué des analyses de sensibilité. RéSULTATS: Les cohortes finales ont inclus 123 695 personnes atteintes de cancer du sein, 98 809 atteintes de cancer colorectal et 116 232 atteintes de cancer du poumon. La survie des sujets ayant des DI/TD a été significativement moins bonne que celle des sujets sans DI/TD. Les rapports de risques instantanés ajustés pour les décès de toutes causes étaient 2,74 fois (IC de 95 % 2,41‒3,12), 2,42 fois (IC de 95 % 2,18‒2,68) et 1,49 fois (IC de 95 % 1,34‒1,66) plus élevés chez les personnes atteintes de cancer du sein, du colorectum et du poumon et ayant des DI/TD que chez les personnes sans DI/TD. Ces constatations ressortent pour tous les décès attribuables à des cancers particuliers. Avec peu d'exceptions, la survie moins bonne pour les personnes ayant des DI/TD persistait quel que soit le stade au moment du diagnostic. CONCLUSION: La survie au cancer était moins bonne chez les personnes ayant des DI/TD que chez celles n'ayant pas de DI/TD. Il est impératif d'identifier les facteurs et les structures responsables de ces disparités dans la survie et d'intervenir en conséquence.

Stage IV breast, colorectal, and lung cancer at diagnosis in adults living with intellectual or developmental disabilities: A population-based cross-sectional study.

BACKGROUND: Cancer is a leading cause of death among people living with intellectual or developmental disabilities (IDD). Although studies have documented lower cancer screening rates, there is limited epidemiological evidence quantifying potential diagnostic delays. This study explores the risk of metastatic cancer stage for people with IDD compared to those without IDD among breast (female), colorectal, and lung cancer patients in Canada. METHODS: Separate population-based cross-sectional studies were conducted in Ontario and Manitoba by linking routinely collected data. Breast (female), colorectal, and lung cancer patients were included (Manitoba: 2004-2017; Ontario: 2007-2019). IDD status was identified using established administrative algorithms. Modified Poisson regression with robust error variance models estimated associations between IDD status and the likelihood of being diagnosed with metastatic cancer. Adjusted relative risks were pooled between provinces using random-effects meta-analyses. Potential effect modification was considered. RESULTS: The final cohorts included 115,456, 89,815, and 101,811 breast (female), colorectal, and lung cancer patients, respectively. Breast (female) and colorectal cancer patients with IDD were 1.60 and 1.44 times more likely to have metastatic cancer (stage IV) at diagnosis compared to those without IDD (relative risk [RR], 1.60; 95% confidence interval [CI], 1.16-2.20; RR, 1.44; 95% CI, 1.24-1.67). This increased risk was not observed in lung cancer. Significant effect modification was not observed. CONCLUSIONS: People with IDD were more likely to have stage IV breast and colorectal cancer identified at diagnosis compared to those without IDD. Identifying factors and processes contributing to stage disparities such as lower screening rates and developing strategies to address diagnostic delays is critical.

Engineered adult stem cells: Current clinical trials status of disease treatment.

Regenerative medicine is an interdisciplinary field involving the process of replacing and regenerating cells/tissues or organs by integrating medicine, science, and engineering principles to enhance the intrinsic regenerative capacity of the host. Recently, engineered adult stem cells have gained attention for their potential use in regenerative medicine by reducing inflammation and modulating the immune system. This chapter introduces adult stem cell engineering and chimeric antigen receptor T cells (CAR T) gene therapy and summarises current engineered stem cell- and extracellular vesicles (EVs)-focused clinical trial studies that provide the basis for the proposal of a personalised medicine approach to diseases diagnosis and treatment.

Impact of decompensated cirrhosis in children: A population-based study.

Background: We describe the proportion of children with compensated cirrhosis who develop decompensation in Ontario, Canada over the past two decades. Methods: This is a retrospective population-based cohort study using routinely collected health care data from Ontario, Canada held at ICES during 1997-2017. Diagnosis of cirrhosis was made using validated ICES definition, and decompensation events were defined according to validated coding. Rates of decompensation, type of decompensation, and incidence of liver transplantation after decompensation were analyzed. Databases were linked at the individual level and analyzed at ICES-Queen's. Results: A total of 2,755 children with compensated cirrhosis were included and 9% (253) developed decompensation over a median follow-up of 7 years. Children most likely to suffer decompensation were younger (median age 10 versus 4 years, p < 0.001) and female (45% versus 52%, p = 0.03). Ascites (137/253, 54%) was the most frequent complication. 199/2755 (7%) of children with cirrhosis received liver transplantation, of which 64% (128/199) occurred after a decompensation event. Overall, a total of 132 (4.7%) deaths occurred during the study period, with 55 deaths following a decompensating event. Conclusion: We present the first study to describe rates of decompensation, type, and rate of liver transplantation after decompensation in pediatric cirrhosis at the population level. To improve the care of children with liver disease, early detection of liver disease, early initiation of specific treatments as well as identification of children who are at risk of becoming decompensated are crucial.

Surgeon Thyroidectomy Case Volume Impacts Disease-free Survival in the Management of Thyroid Cancer.

OBJECTIVES: To assess the association between surgeons thyroidectomy case volume and disease-free survival (DFS) for patients with well-differentiated thyroid cancer (WDTC). A secondary objective was to assess a surgeon volume cutoff to optimize outcomes in those with WDTC. We hypothesized that surgeon volume will be an important predictor of DFS in patients with WDTC after adjusting for hospital volume and sociodemographic and clinical factors. METHODS: In this retrospective population-based cohort study, we identified WDTC patients in Ontario, Canada, who underwent thyroidectomy confirmed by both hospital-level and surgeon-level administrative data between 1993 and 2017 (N = 37,233). Surgeon and hospital volumes were calculated based on number of cases performed in the year prior by the physician and at an institution performing each case, respectively and divided into quartiles. A multilevel hierarchical Cox regression model was used to estimate the effect of volume on DFS. RESULTS: A crude model without patient or treatment characteristics demonstrated that both higher surgeon volume quartiles (p < 0.001) and higher hospital volume quartiles (p < 0.001) were associated with DFS. After controlling for clustering and patient/treatment covariates and hospital volume, moderately low (18-39/year) and low (0-17/year) volume surgeons (hazard ratios [HR]: 1.23, 95% confidence interval [CI]: 1.09-1.39 and HR: 1.34, 95% CI: 1.17-1.53 respectively) remained an independent statistically significant negative predictor of DFS. CONCLUSION: Both high-volume surgeons and hospitals are predictors of better DFS in patients with WDTC. DFS is higher among surgeons performing more than 40 thyroidectomies a year. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:S1-S15, 2023.

Mode of conception in patients with endometriosis and adverse pregnancy outcomes: a population-based cohort study.

OBJECTIVE: To evaluate the association between endometriosis and adverse pregnancy outcomes. DESIGN: Population-based retrospective cohort study using linked universal health databases through ICES Ontario. PATIENT(S): All singleton pregnancies with an estimated date of confinement between October 2006 and February 2014. INTERVENTION(S): Endometriosis was determined based on a surgical and/or medical diagnosis (defined as an in-hospital admission or surgery with a diagnosis code of International Classification of Diseases [ICD]9-617 or ICD10-N80 and/or 2 medical consults billed as ICD9-617). MAIN OUTCOME MEASURE(S): The association between endometriosis and pregnancy outcomes was quantified by relative risks, derived using modified Poisson regression, and adjusted for maternal age, income quintiles, and history of fibroids (aRR). Mediation analysis was conducted to estimate direct effects of endometriosis diagnosis and indirect effects through mode of conception, namely: infertility without fertility treatment (known infertility but conceived without assistance), ovulation induction or intrauterine insemination, and in vitro fertilization or intracytoplasmic sperm injection, relative to unassisted conception. RESULT(S): A total of 19,099 pregnancies had an antecedent diagnosis of endometriosis, while 768,350 did not. Mean time (standard deviation) from endometriosis diagnosis to the index pregnancy was 5.6 (4.3) years. Endometriosis was associated with an increased risk of hypertensive disorders of pregnancy (aRR, 1.09; 95% confidence interval [CI], 1.02-1.16), preterm birth <37 weeks (aRR, 1.26; 95% CI, 1.20-1.33), early preterm birth <34 weeks (aRR, 1.33; 95% CI, 1.17-1.50), placenta previa (aRR, 2.07; 95% CI, 1.84-2.33), placenta abruption (aRR, 1.55; 95% CI, 1.31-1.83), other placental disorders (aRR, 1.77; 95% CI, 1.36-2.30), cesarean delivery (aRR, 1.18; 95% CI, 1.16-1.21), and stillbirth (aRR, 1.32; 95% CI, 1.09-1.59). Mediation analysis suggests that endometriosis directly affects most adverse pregnancy outcomes studied, except for stillbirth where infertility diagnosis or fertility treatment indirectly accounted for part of the increased risk. CONCLUSION(S): Endometriosis was associated with adverse pregnancy, independent of infertility diagnosis, or fertility treatment. Future studies should investigate the mechanisms of action and potential interventions.

Encouraging impacts of an Open Education Resource Degree Initiative on college students' progress to degree.

Textbooks are traditional and useful learning resources for college students, but commercial texts books have been widely criticized for their high costs, restricted access, limited flexibility, and uninspiring learning experiences. Open Education Resources (OER) are an alternative to commercial textbooks that have the potential to increase college affordability, access, and instructional quality. The current study examined how an OER degree-or pathway of OER courses that meet the requirements for a degree program-impacted students' progress to degree at 11 US community colleges. We conducted quasi-experimental impact studies and meta-analysis examining whether OER course enrollment was associated with differences in credit accumulation and cumulative GPA over multiple terms. Overall, we found a positive effect of OER degrees on credit accumulation and no significant difference on cumulative GPA. Taken together, these results suggest students are maintaining their GPAs despite taking more courses, on average. This suggests that students taking OER courses were making faster progress towards degrees than their peers who took no OER courses.

Infertility Consults in Immigrant and Refugee Women in Ontario: Population-Based Cohort Study.

Though immigrant women comprise a growing portion of the Canadian population, there remains a lack of information on the rates of infertility diagnosis in this group. Our study aimed to investigate the differences in rates of infertility consults between refugee, non-refugee immigrant, and Canadian-born women. We conducted a population-based matched cohort study in women 15-45 years of age in Ontario. Immigration status was defined as refugee, non-refugee immigrant, and Canadian-born woman. Refugee and non-refugee immigrant women were matched by age and residence in the same Local Health Integration Network (LHIN) to two Canadian-born women. The cohort was followed for 2 years for occurrence of infertility consult. Proportion of infertility consults by immigration status was calculated and differences between groups were assessed using standardized differences (SD). Modified Poisson regression was used to calculate the relative risk (RR) for infertility consults by immigration status after adjusting for confounding variables. Our results showed an increased proportion of infertility consults among both refugees (4.7%) and non-refugee immigrant women (5.8%) compared to their Canadian-born matches (2.8% and 3.2%, respectively), with SD ≧ 0.1 in most stratified age groups, denoting a meaningful statistical difference. In the multivariable analysis, relative to Canadian-born women, the RR for fertility consults was increased in refugee women (RR 1.66, CI 95% 1.58-1.75), and non-refugee immigrants (RR 1.77, 95% CI 1.74-1.80). These findings may be explained by immigrant women originating from areas with higher infertility rates, or their experience of higher than average stress levels, a known risk factor for infertility.

An evaluation of a first-of-its-kind hybrid law degree program.

There are few published studies investigating the effectiveness of hybrid formats at the program level in graduate legal education. A hybrid Juris Doctorate (J.D.) program launched by a Midwestern institution was the first ABA-accredited law degree program with a substantial online learning component. This study takes a mixed methods approach (both quantitative and qualitative) to evaluate student outcomes and the extent to which the hybrid program expands access to legal education. The study compares student outcomes in the hybrid program with full-time and part-time traditional, in-person programs at the same institution. After three terms of data collection, findings suggest that student outcomes and engagement are comparable across formats when controlling for student background characteristics and prior achievement. Evidence suggests that the hybrid option may increase access to legal education but is insufficient to determine whether the hybrid program will increase availability of legal services in underserved areas.

The Impact of Hospital Surgical Volume on Healthcare Utilization Outcomes After Pediatric Thyroidectomy.

BACKGROUND: A positive relationship between an individual surgeon's operative volume and clinical outcomes after pediatric and adult thyroidectomy is well-established. The impact of a hospital's pediatric operative volume on surgical outcomes and healthcare utilization, however, are infrequently reported. We investigated associations between hospital volume and healthcare utilization outcomes following pediatric thyroidectomy in Canada's largest province, Ontario. METHODS: Retrospective analysis of administrative and health-related population-level data from 1993 to 2017. A cohort of 1908 pediatric (<18 years) index thyroidectomies was established. Hospital volume was defined per-case as thyroidectomies performed in the preceding year. Healthcare utilization outcomes: length of stay (LOS), same day surgery (SDS), readmission, and emergency department (ED) visits were measured. Multivariate analysis adjusted for patient-level, disease and hospital-level co-variates. RESULTS: Hospitals with the lowest volume of pediatric thyroidectomies, accounted for 30% of thyroidectomies province-wide and performed 0-1 thyroidectomies/year. The highest-volume hospitals performed 19-60 cases/year. LOS was 0.64 days longer in the highest, versus the lowest quartile. SDS was 83% less likely at the highest, versus the lowest quartile. Hospital volume was not associated with rate of readmission or ED visits. Increased ED visits were, however, associated with male sex, increased material deprivation, and rurality. CONCLUSIONS: Increased hospital pediatric surgical volume was associated with increased LOS and lower likelihood of SDS. This may reflect patient complexity at such centers. In this cohort, low-volume hospitals were not associated with poorer healthcare utilization outcomes. Further study of groups disproportionately accessing the ED post-operatively may help direct resources to these populations.

Increasing Incidence of Cirrhosis Over the Past 2 Decades Among Children in Ontario, Canada.

INTRODUCTION: We describe the incidence of cirrhosis in the general pediatric population. METHODS: This is a population-based study using health-care data from Ontario, Canada, between 1997 and 2017. Age-adjusted and sex-adjusted standardized incidence rates were described, and age-period-cohort modeling approach was used to estimate the independent effect of birth cohort. RESULTS: In total, 2,966 new diagnoses of cirrhosis among children were identified at a median age of 9 years. The incidence rate increased almost 4-fold over the study period (2.7/100,000 person-years in 1997 vs 10.6/100,000 person-years in 2017) with the highest increase seen in children younger than 1 year. DISCUSSION: In this first population-based study in children, the incidence of cirrhosis has increased dramatically over the past 2 decades.

Use of imaging for active surveillance in testicular cancer: Is real-world practice concordant with guidelines?

INTRODUCTION: Imaging is an integral component of active surveillance (AS) following orchiectomy for stage 1 non-seminoma (NSGCT) and seminoma germ cell tumors. In this population-based study, we describe use of imaging among patients with early-stage testicular cancer and evaluate whether they are concordant with guideline recommendations. METHODS: This is a population-based, retrospective cohort study to describe use of imaging among all patients with early-stage testicular cancer treated with AS in the Canadian province of Ontario. The Ontario Cancer Registry was linked to electronic records of treatment to identify use of chest and abdomen/pelvis imaging. Data from 2000-2010 were included, with followup for up to five years for patients with non-seminoma and 10 years for patients with seminoma. The key outcome of interest was the frequency of imaging at temporal milestones following orchiectomy. Compared to the most contemporaneous guidelines in Ontario, any discordant frequency of imaging was defined as underuse or overuse. Substantial under- or overuse was defined as >1 imaging test less/ more than what was recommended during a 12-month period. RESULTS: The study population included 569 patients with NSGCT (median age 28) and 1107 with seminoma (median age 37). Among patients with NSGCT, adherence with body imaging was low in years 1-3 of surveillance (range 26-37%, predominantly underuse) and higher in years 4-5 (63-67%, predominantly overuse). Adherence with chest imaging was even lower (range 11-34% during years 1-5). Among patients with seminoma, adherence with abdominal and chest imaging was relatively stable and comparable throughout the 10-year followup period (range 23-47% abdomen and 28-47% chest). Multivariable analysis confirmed that underuse of imaging was more common in recent years. NSGCT histology was associated with underuse in years 1-2 but overse in years 3-5. CONCLUSIONS: In routine clinical practice, patients with testicular cancer commonly receive imaging discordant to the protocol for AS, with a substantial proportion receiving both under- and overuse at various times during surveillance followup.

Surgical Case Volume has an Impact on Outcomes for Patients with Lateral Neck Disease in Thyroid Cancer.

BACKGROUND: This study aimed to assess whether surgical case volume for lateral neck dissection has an impact on the survival of patients who have well-differentiated thyroid cancer (WDTC) with lateral cervical node metastases. The authors used a population-based cohort study design. METHODS: The study cohort consisted of WDTC patients in Ontario Canada who underwent thyroidectomy and lateral neck dissection. These patients were identified using both hospital- and surgeon-level administrative data between 1993 and 2017 (n = 1832). Surgeon and hospital volumes were calculated based on the number of cases managed in the year before the procedure by the physician and at the institution managing each case, respectively, and divided into tertiles. Multilevel Cox regression models were used to estimate the effect of volume on disease-free survival (DFS). RESULTS: A crude model without patient or treatment characteristics demonstrated that DFS was associated with both higher surgeon volume tertiles (p < 0.01) and higher hospital volume tertiles (p < 0.01). After control for clustering, patient/treatment covariates, and hospital volume, the lowest surgeon volume tertile (range, 0-20/year; mean, 6.5/year) remained an independent statistically significant negative predictor of DFS (hazard ratio, 1.71; 95 % confidence interval, 1.22-2.4; p < 0.01). CONCLUSION: Surgeon lateral neck dissection case volume is a predictor of better DFS for thyroid cancer patients, with the lowest surgeon volume tertile (<20 neck dissections per year) demonstrating poorer DFS.

Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics.

Developing robust methodology for the sustainable production of red blood cells in vitro is essential for providing an alternative source of clinical-quality blood, particularly for individuals with rare blood group phenotypes. Immortalized erythroid progenitor cell lines are the most promising emergent technology for achieving this goal. We previously created the erythroid cell line BEL-A from bone marrow CD34+ cells that had improved differentiation and enucleation potential compared to other lines reported. In this study we show that our immortalization approach is reproducible for erythroid cells differentiated from bone marrow and also from far more accessible peripheral and cord blood CD34+ cells, consistently generating lines with similar improved erythroid performance. Extensive characterization of the lines shows them to accurately recapitulate their primary cell equivalents and provides a molecular signature for immortalization. In addition, we show that only cells at a specific stage of erythropoiesis, predominantly proerythroblasts, are amenable to immortalization. Our methodology provides a step forward in the drive for a sustainable supply of red cells for clinical use and for the generation of model cellular systems for the study of erythropoiesis in health and disease, with the added benefit of an indefinite expansion window for manipulation of molecular targets.

A Population-Based Analysis of Outpatient Thyroidectomy: Safe and Under-Utilized.

OBJECTIVES/HYPOTHESIS: Performance of thyroidectomy on an outpatient basis has gained popularity although many jurisdictions have not shifted their practice despite a strong safety profile. We sought to assess the uptake and safety of outpatient thyroidectomy in Ontario. STUDY DESIGN: Retrospective cohort study. METHODS: This was a population-based retrospecive cohort of adult patients undergoing hemithyroidectomy or total thyroidectomy between 1993 and 2017 in Ontario, Canada. Outpatient surgery was defined as discharge home on the same day of surgery. Outcomes of interest include 30-day all cause death, hematoma, emergency department use, and readmission. To adjust for confounding, propensity scores were calculated. Logistic regression models with inverse probability of treatment weighting (IPTW) were then used to estimate the exposure-outcome relationship. RESULTS: The final cohort consisted of 81,199 patients: 8,442 underwent same day surgery and 72,757 were admitted. The proportion of patients undergoing outpatient thyroidectomy increased overtime (2.3% in 1993-1994 to 17.8% in 2016-2017). Factors associated with higher odds of outpatient thyroidectomy included: younger age, less material deprivation, less comorbidities, and higher surgeon volume. The absolute number of deaths (≤5) and hematomas (64, 0.8%) in the outpatient cohort was low. After IPTW adjustment, patients with outpatient management had lower odds of neck hematoma (OR 0.73[95CI% 0.58-0.93)], but higher odds of emergency department use (OR 1.67[95%CI 1.56-1.79]). CONCLUSIONS: Outpatient thyroidectomy is not associated with an increased mortality risk. Less than one in five patients undergo outpatient thyroidectomy in Ontario, despite a well-established safety profile. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2625-2633, 2021.

Mental Health Resource Use Among Patients Undergoing Curative Intent Treatment for Bladder Cancer.

BACKGROUND: Patients with bladder cancer may experience mental health distress. Mental health-care service (MHS) use can quantify the magnitude of the problem. METHODS: The Ontario Cancer Registry was used to identify all patients with bladder cancer treated with curative-intent cystectomy or radiotherapy in Ontario, Canada (2004-2013). Population-level databases were used to identify MHS use (visits to general practitioner, psychiatrist, emergency department, or hospitalization). Generalized estimating equations were used to compare rates of MHS use. Baseline, peritreatment, and posttreatment MHS use were defined as visits from 2 years to 3 months before, 3 months before to 3 months after, and from 3 months after to 2 years after start of treatment, respectively. RESULTS: From 2004 to 2013, 4296 patients underwent cystectomy (n = 3332) or curative-intent radiotherapy (n = 964). Compared with baseline, the rate of MHS use was higher in the peritreatment (adjusted rate ratio [aRR] = 1.64, 95% confidence interval [CI] = 1.48 to 1.82) and posttreatment periods (aRR = 1.45, 95% CI =1.30 to 1.63). By 2 years posttreatment, 24.6% (95% CI = 23.4% to 25.9%) of all patients had MHS use. Patients with baseline MHS use had substantially higher MHS use in the peritreatment (aRR = 5.77, 95% CI = 4.86 to 6.86) and posttreatment periods (aRR = 4.58, 95% CI = 3.78 to 5.55). Female patients had higher use MHS use overall, but males had a higher incremental increase in the posttreatment period compared with baseline (2-sided Pinteraction = .02). Male patients had a statistically significant increase in MHS use following surgery or radiotherapy, whereas female patients only had an increase following surgery. CONCLUSIONS: MHS use is common among patients undergoing treatment for bladder cancer, particularly in the peritreatment period. Screening for mental health concerns in this population is warranted.

Field-testing an iCST touch-screen application with people with dementia and carers: a mixed method study.

OBJECTIVES: To test the individual Cognitive Stimulation Therapy (iCST) application with people with dementia and carers in order to modify and refine the application, and improve its usability. In an iterative development process, two different prototypes were used to elicit the subjects' views and preferences. This application may address the current need for more innovative approaches to support people with dementia and their carers. METHODS: An opportunistic sample of 13 people with dementia and 13 carers participated in four focus groups and ten semi-structured interviews to obtain feedback in key areas, including the layout and content of the application, and the experience of its use as a dyad. Data were audio-recorded, transcribed and analysed thematically. An additional 18 people with dementia and 16 carers completed a short usability and acceptability questionnaire regarding a subsequent version of the iCST application prototype. RESULTS: Most participants expressed enthusiasm about the iCST application, its usability, design, and content. Participants highlighted the importance of adaptability to individual preferences, indicating a need for a wider range of activities and flexibility in the use of the application. Furthermore, participants reported perceived benefits, including mental stimulation, quality time spent together, and enjoyment. The application was rated slightly better by carers than people with dementia in terms of usability and acceptability. CONCLUSIONS: This study gives insights from people with dementia and carers concerning the usability, feasibility, and perceived benefits of the iCST application. The feedback will be incorporated in an updated version of the iCST application for commercial release.