A population-based analysis of the management of symptoms of depression among patients with stage IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

PURPOSE: Patients with lung cancer can experience significant psychological morbidities including depression. We characterize patterns and factors associated with interventions for symptoms of depression in stage IV non-small cell lung cancer (NSCLC). METHODS: We conducted a population-based cohort study using health services administrative data in Ontario, Canada of stage IV NSCLC diagnosed from January 2007 to September 2018. A positive symptom of depression score was defined by reporting at least one ESAS (Edmonton Symptom Assessment System) depression score ≥ 2 following diagnosis until the end of follow-up (September 2019). Patient factors included age, sex, comorbidity burden, rurality of residence, and neighbourhood income quintile. Interventions included psychiatry assessment, psychology referral, social work referral and anti-depressant medical therapy (for patients ≥ 65 years with universal drug coverage). Multivariable modified Poisson regression models were used to examine the association between patient factors and intervention use for patients who reported symptoms of depression. RESULTS: In the cohort of 13,159 patients with stage IV NSCLC lung cancer, symptoms of depression were prevalent (71.4%, n = 9,397). Patients who reported symptoms of depression were more likely to receive psychiatry assessment/psychology referral (7.8% vs 3.5%; SD [standardized difference] 0.19), social work referral (17.4% vs 11.9%; SD 0.16) and anti-depressant prescriptions (23.8% vs 13.8%; SD 0.26) when compared to patients who did not report symptoms of depression respectively. In multivariable analyses, older patients were less likely to receive any intervention. Females were more likely to obtain a psychiatry assessment/psychology referral or social work referral. In addition, patients from non-major urban or rural residences were less likely to receive psychiatry assessment/psychology referral or social work referral, however patients from rural residences were more likely to be prescribed anti-depressants. CONCLUSIONS: There is high prevalence of symptoms of depression in stage IV NSCLC. We identify patient populations, including older patients and rural patients, who are less likely to receive interventions that will help identifying and screening for symptoms of depression.

Pain and Interventions in Stage IV Non-Small Cell Lung Cancer: A Province-Wide Analysis.

Pain is a common symptom in stage IV non-small cell lung cancer (NSCLC). The objective of the study was to examine the use of interventions and factors associated with interventions for pain. A population-based cohort study in Ontario, Canada was conducted with patients diagnosed with stage IV NSCLC from January 2007 to September 2018. An Edmonton Symptom Assessment System (ESAS) score of ≥4 defined moderate-to-severe pain following diagnosis. The study cohort included 13,159 patients, of which 68.5% reported at least one moderate-to-severe pain score. Most patients were assessed by a palliative care team (85.4%), and the majority received radiation therapy (73.2%). The use of nerve block was rare (0.8%). For patients ≥65 years of age who had drug coverage, 59.6% received an opiate prescription. Patients with moderate-to-severe pain were more likely to receive palliative assessment or radiation therapy compared to patients with none or mild pain. Patients aged ≥70 years and with a greater comorbidity burden were associated with less likelihood to receive radiation therapy. Patients from rural/non-major urban residence and with a greater comorbidity burden were also less likely to receive palliative care assessment. Factors associated with interventions for pain are described to inform future symptom management in this population.

Ensuring Superior Reporting of Radiation Therapy Noninferiority Trials: A Systematic Review.

Purpose: Although the frequency of noninferiority trials is increasing, the consistency of the reporting of these trials can vary. The aim of this systematic review was to assess the reporting quality of radiation therapy noninferiority trials. Methods and Materials: The PubMed, Embase, and Cochrane databases were queried for randomized controlled radiation therapy trials with noninferiority hypotheses published in English between January 2000 and July 2022, and this was performed by an information scientist. Descriptive statistics were used to summarize data. Results: Of 423 records screened, 59 (14%) were included after full-text review. All were published after 2003 and open label. The most common primary cancer type was breast (n = 15, 25%). Altered radiation fractionation (n = 26, 45%) and radiation de-escalation (n = 11, 19%) were the most common types of interventions. The most common primary endpoints were locoregional control (n = 17, 29%) and progression-free survival (n = 14, 24%). Fifty-three (90%) reported the noninferiority margin, and only 9 (17%) provided statistical justification for the margin. The median absolute noninferiority margin was 9% (interquartile range, 5%-10%), and the median relative margin was 1.51 (interquartile range, 1.33-2.04). Sample size calculations and confidence intervals were reported in 54 studies (92%). Both intention-to-treat and per-protocol analyses were reported in 27 studies (46%). In 31 trials (53%), noninferiority of the primary endpoint was reached. Conclusions: There was variability in the reporting of key components of noninferiority trials. We encourage consideration of additional statistical reasoning such as guidelines or previous trials in the selection of the noninferiority margin, reporting both absolute and relative margins, and the avoidance of statistically vague or misleading language in the reporting of future noninferiority trials.

Top Ten Lessons Learned from Trials in Oligometastatic Cancers.

Recent evidence supports the role of aggressive local treatment in the oligometastatic setting. In this review, we discuss the top 10 lessons we have learned from trials in oligometastatic cancers. Major lessons learned pertain to definitions of oligometastatic disease, outcomes, toxicity, costs, and the combination of ablative therapies with systemic therapy, including immunotherapy. Barriers to accrual for trials and upcoming phase III trials are also reviewed. These lessons may help to inform clinical practice and may be the basis for future research in the oligometastatic space.

Delayed Treatment of Retroclival Meningioma in a 70-year-old Female.

We report a case of a 70-year-old female who presented with a four-year history of progressive headaches in the occipital area. MRI revealed a right inferior clival meningioma. Treatment was delayed for over a year due to multiple referrals resulting in the development of new symptoms including decreased balance, generalized weakness, and difficulty swallowing.

Socioeconomic Status and Kidney Transplant Outcomes in a Universal Healthcare System: A Population-based Cohort Study.

BACKGROUND: Conflicting evidence exists regarding the relationship between socioeconomic status (SES) and outcomes after kidney transplantation. METHODS: We conducted a population-based cohort study in a publicly funded healthcare system using linked administrative healthcare databases from Ontario, Canada to assess the relationship between SES and total graft failure (ie, return to chronic dialysis, preemptive retransplantation, or death) in individuals who received their first kidney transplant between 2004 and 2014. Secondary outcomes included death-censored graft failure, death with a functioning graft, all-cause mortality, and all-cause hospitalization (post hoc outcome). RESULTS: Four thousand four hundred-fourteen kidney transplant recipients were included (median age, 53 years; 36.5% female), and the median (25th, 75th percentile) follow-up was 4.3 (2.1-7.1) years. In an unadjusted Cox proportional hazards model, each CAD $10000 increase in neighborhood median income was associated with an 8% decline in the rate of total graft failure (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.87-0.97). After adjusting for recipient, donor, and transplant characteristics, SES was not significantly associated with total or death-censored graft failure. However, each CAD $10000 increase in neighborhood median income remained associated with a decline in the rate of death with a functioning graft (adjusted (a)HR, 0.91; 95% CI, 0.83-0.98), all-cause mortality (aHR, 0.92; 95% CI, 0.86-0.99), and all-cause hospitalization (aHR, 0.95; 95% CI, 0.92-0.98). CONCLUSIONS: In conclusion, in a universal healthcare system, SES may not adversely influence graft health, but SES gradients may negatively impact other kidney transplant outcomes and could be used to identify patients at increased risk of death or hospitalization.

Predicting 3-Year Survival in Patients Receiving Maintenance Dialysis: An External Validation of iChoose Kidney in Ontario, Canada.

BACKGROUND: Many patients with end-stage kidney disease (ESKD) do not appreciate how their survival may differ if treated with a kidney transplant compared with dialysis. A risk calculator (iChoose Kidney) developed and validated in the United States provides individualized mortality estimates for different treatment options (dialysis vs living or deceased donor kidney transplantation). The calculator can be used with patients and families to help patients make more educated treatment decisions. OBJECTIVE: To validate the iChoose Kidney risk calculator in Ontario, Canada. DESIGN: External validation study. SETTING: We used several linked administrative health care databases from Ontario, Canada. PATIENTS: We included 22 520 maintenance dialysis patients and 4505 kidney transplant recipients. Patients entered the cohort between 2004 and 2014. MEASUREMENTS: Three-year all-cause mortality. METHODS: We assessed model discrimination using the C-statistic. We assessed model calibration by comparing the observed versus predicted mortality risk and by using smoothed calibration plots. We used multivariable logistic regression modeling to recalibrate model intercepts using a correction factor, when appropriate. RESULTS: In our final version of the iChoose Kidney model, we included the following variables: age (18-80 years), sex (male, female), race (white, black, other), time on dialysis (<6 months, 6-12 months, >12 months), and patient comorbidities (hypertension, diabetes, and/or cardiovascular disease). Over the 3-year follow-up period, 33.3% of dialysis patients and 6.2% of kidney transplant recipients died. The discriminatory ability was moderate (C-statistic for dialysis: 0.70, 95% confidence interval [CI]: 0.69-0.70, and C-statistic for transplant: 0.72, 95% CI: 0.69-0.75). The 3-year observed and predicted mortality estimates were comparable and even more so after we recalibrated the intercepts in 2 of our models (dialysis and deceased donor kidney transplantation). As done in the United States, we developed a Canadian Web site and an iOS application called Dialysis vs. Kidney Transplant- Estimated Survival in Ontario. LIMITATIONS: Missing data in our databases precluded the inclusion of all variables that were in the original iChoose Kidney (ie, patient ethnicity and low albumin). We were unable to perform all preplanned analyses due to the limited sample size. CONCLUSIONS: The original iChoose Kidney risk calculator was able to adequately predict mortality in this Canadian (Ontario) cohort of ESKD patients. After minor modifications, the predictive accuracy improved. The Dialysis vs. Kidney Transplant- Estimated Survival in Ontario risk calculator may be a valuable resource to help ESKD patients make an informed decision on pursuing kidney transplantation.

CONTEXTE: Plusieurs patients atteints d'insuffisance rénale terminale (IRT) ignorent à quel point leurs chances de survie varient selon qu'ils sont traités par dialyse ou par une greffe rénale. Un modèle de prévision des risques (l'outil de calcul iChoose Kidney), développé et validé aux États-Unis, fournit une estimation personnalisée des chances de survie selon les différentes modalités de traitement (dialyse ou greffe d'un rein provenant d'un donneur vivant ou décédé). L'outil de calcul peut être employé par les patients et leurs familles pour les aider à prendre une décision plus éclairée au sujet du traitement. OBJECTIF DE L'ÉTUDE: Valider l'outil de calcul iChoose Kidney dans une cohorte de patients de l'Ontario, au Canada. TYPE D'ÉTUDE: Une étude de validité externe. CADRE DE L'ÉTUDE: Plusieurs bases de données couplées du système de santé ontarien (Canada). PATIENTS: Un total de 22 520 patients dialysés et de 4 505 receveurs d'une greffe de rein ont été inclus entre 2004 et 2014. MESURES: La mortalité toutes causes sur une période de trois (3) ans. MÉTHODOLOGIE: Nous avons évalué le pouvoir discriminant du modèle à l'aide de la statistique C. L'étalonnage du modèle a été établi en comparant les risques de mortalité observé et prédit, et à l'aide de courbes d'étalonnage lissées. Des modèles de régression logistique multivariés ont été employés pour réétalonner les valeurs à l'origine en utilisant au besoin un facteur de correction. RÉSULTATS: Notre version définitive du modèle de prévision inclut les variables suivantes : l'âge du patient (18 à 80 ans), son genre, sa race (blanc, noir, autre), son expérience en dialyse (moins de 6 mois, entre 6 et 12 mois, plus de 12 mois) et ses comorbidités (hypertension, diabète et maladies cardiovasculaires). Au cours des trois ans de suivi, 33,3 % des patients dialysés et 6,2 % des receveurs d'une greffe sont décédés. Le pouvoir discriminant s'est avéré modéré avec une valeur de statistique C de 0,70 (IC 95 % : 0,69-0,70) pour la dialyse et de 0,72 (IC 95 % : 0,69-0,75) pour les greffes. Les taux de mortalité observé et estimé au cours des trois ans étaient comparables, et davantage après le réétalonnage des valeurs à l'origine dans deux de nos modèles (dialyse et receveur d'un rein d'un donneur décédé). Comme aux États-Unis, nous avons développé un site Web et une application iOS canadiens nommés Dialysis vs. Kidney Transplant-Estimated Survival in Ontario. LIMITES: Des informations manquantes dans les bases de données consultées nous ont empêchés de tenir compte de toutes les variables incluses dans le modèle iChoose Kidney original, notamment l'origine ethnique du patient et les valeurs d'albuminurie. De plus, la taille restreinte de l'échantillon ne nous a pas permis de procéder à toutes les analyses prévues. CONCLUSION: La version originale du modèle de prévision des risques iChoose Kidney a prédit adéquatement le risque de mortalité dans une cohorte de patients ontariens atteints d'IRT. La précision du pouvoir prédictif du modèle s'est améliorée à la suite d'ajustements mineurs. L'outil Dialysis vs. Kidney Transplant-Estimated Survival in Ontario pourrait ainsi devenir une ressource précieuse pour les patients ontariens atteints d'IRT, pour les aider à prendre une décision éclairée dans leur choix d'une modalité de traitement.

ESRD among Immigrants to Ontario, Canada: A Population-Based Study.

Background The epidemiology of ESRD requiring maintenance dialysis (ESRD-D) in large, diverse immigrant populations is unclear.Methods We estimated ESRD-D prevalence and incidence among immigrants in Ontario, Canada. Adults residing in Ontario in 2014 were categorized as long-term Canadian residents or immigrants according to administrative health and immigration datasets. We determined ESRD-D prevalence among these adults and calculated age-adjusted prevalence ratios (PRs) comparing immigrants to long-term residents. Among those who immigrated to Ontario between 1991 and 2012, age-adjusted ESRD-D incidence was calculated by world region and country of birth, with immigrants from Western nations as the referent group.Results Among 1,902,394 immigrants and 8,860,283 long-term residents, 1700 (0.09%) and 8909 (0.10%), respectively, presented with ESRD-D. Age-adjusted ESRD-D prevalence was higher among immigrants from sub-Saharan Africa (PR, 2.17; 95% confidence interval [95% CI], 1.84 to 2.57), Latin America and the Caribbean (PR, 2.11; 95% CI, 1.90 to 2.34), South Asia (PR, 1.45; 95% CI, 1.32 to 1.59), and East Asia and the Pacific (PR, 1.34; 95% CI, 1.22 to 1.46). Immigrants from Somalia (PR, 4.18; 95% CI, 3.11 to 5.61), Trinidad and Tobago (PR, 2.88; 95% CI, 2.23 to 3.73), Jamaica (PR, 2.88; 95% CI, 2.40 to 3.44), Sudan (PR, 2.84; 95% CI, 1.53 to 5.27), and Guyana (PR, 2.69; 95% CI, 2.19 to 3.29) had the highest age-adjusted ESRD-D PRs relative to long-term residents. Immigrants from these countries also exhibited higher age-adjusted ESKD-D incidence relative to Western Nations immigrants.Conclusions Among immigrants in Canada, those from sub-Saharan Africa and the Caribbean have the highest ESRD-D risk. Tailored kidney-protective interventions should be developed for these susceptible populations.

Impact of Injectable Furosemide Hospital Shortage on Congestive Heart Failure Outcomes: A Time Series Analysis.

BACKGROUND: Beginning in February 2012, there was a shortage of injectable furosemide in the province of Ontario, Canada. The objective of this study was to assess the effects of the furosemide shortage on heart failure outcomes in Ontario, Canada. METHODS: We determined which hospitals experienced a shortage of injectable furosemide using an online survey. We then used health administrative data to identify all patients who presented to those hospitals with congestive heart failure. Using 40 months of data from before the shortage, we determined the proportion of patients with heart failure expected to die each month. We then used time series analysis to forecast the 30-day mortality rate during the shortage period and compared it with the observed rate. Secondary outcomes included length of hospital stay, transfer to an intensive care unit, mechanical ventilation during the hospital stay, and risk of 30-day readmission for heart failure. RESULTS: Survey results were obtained for 82% of hospitals, 28 of which experienced a severe shortage of injectable furosemide in the year 2012. The 30-day mortality among patients presenting to these hospitals with congestive heart failure before the shortage period was 11.2%. We forecasted a mortality rate of 11.3% (95% confidence interval, 8.2-14.4) for the shortage period, which was not significantly different from the observed rate of 10.9%. Similarly, we found no significant effect of the shortage on secondary outcomes. CONCLUSIONS: A severe shortage of injectable furosemide did not increase the risk of adverse outcomes among patients who presented to the hospital with congestive heart failure.

The 3-Year Incidence of Gout in Elderly Patients with CKD.

BACKGROUND AND OBJECTIVES: The risk of gout across CKD stages is not well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study using linked health care databases from Ontario, Canada from 2002 to 2010. The primary outcome was the 3-year cumulative incidence of gout, on the basis of diagnostic codes. We presented our results by level of kidney function (eGFR≥90 ml/min per 1.73 m2, 60-89, 45-59, 30-44, 15-29, and chronic dialysis) and by sex. Additional analyses examined the risk of gout adjusting for clinical characteristics, incidence of gout defined by the receipt of allopurinol or colchicine, and gout risk in a subpopulation stratified by the level of eGFR and albuminuria. RESULTS: Of the 282,925 adults aged ≥66 years, the mean age was 75 years and 57.9% were women. The 3-year cumulative incidence of gout was higher in older adults with a lower level of eGFR. In women, the 3-year cumulative incidence of gout was 0.6%, 0.7%, 1.3%, 2.2%, and 3.4%, and in men the values were 0.8%, 1.2%, 2.5%, 3.7%, and 4.6%, respectively. However, patients on chronic dialysis had a lower 3-year cumulative incidence of gout (women 2.0%, men 2.9%) than those with more moderate reductions in kidney function (i.e., eGFR 15-44 ml/min per 1.73 m2). The association between a greater loss of kidney function and a higher risk of diagnosed gout was also evident after adjustment for clinical characteristics and in all additional analyses. CONCLUSIONS: Patients with a lower level of eGFR had a higher 3-year cumulative incidence of gout, with the exception of patients receiving dialysis. Results can be used for risk stratification.