Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Treatment, healthcare utilization and outcomes in patients with glioblastoma in Ontario: a 10-year cohort study.

BACKGROUND AND PURPOSE: Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. Receipt of adjuvant therapies has been shown to exert a significant positive effect on patient survival. Little is known however about how changes in standards of care and healthcare system factors, such as access, affect real-world outcomes. In this study, we provide an overview of GBM in Ontario and examine elements of care, including treatment patterns, healthcare utilization, and overall survival, from 2010 to 2019, to interpret the impact of the changes in practice standards and expansion of the care network within this period. METHODS: Using linked health-administrative databases from Ontario, Canada, we conducted a population-based cohort study to examine the clinical and biological characteristics, treatment, and healthcare utilization patterns of adult GBM patients diagnosed between 2010 and 2019. The primary outcomes were enrollment in adjuvant chemoradiation treatment and 1-, 2-, and 5-year survival. All analyses were performed using the Statistical Analysis Software (SAS). RESULTS: 5392 patients were diagnosed with GBM in Ontario from 2010 to 2019 (58% male, 42% female). The median age at diagnosis was 64. Receipt of adjuvant chemoradiation within one year of diagnosis increased from 51% in 2010 to 63% in 2019. 1-year, 2-year, and 5-year overall survival for all patients remained stable, ranging between 40 and 43%, 15-19%, and 5-7%, respectively. For patients above the age of 65, however, 1-year survival increased from 19% in 2010 to 26% in 2019. INTERPRETATION: Regionalization enabled access to treatment closer to home for many patients. Over the last decade, receipt of adjuvant chemoradiation increased among elderly patients, but the improvement in 1-year overall survival over time was accounted for by sociodemographic and clinical covariates. Our findings support the efforts for regionalization of services to improve accessibility. CONCLUSION: This Ontario-based study provides insight into the effect of practice evolution and healthcare utilization on the overall survival of patients with GBM. Overall survival for most patients with glioblastoma has remained stagnant over the past decade. Changes in treatment standards and expansion of access to treating centres have been associated with prolonged survival in elderly glioblastoma patients.

The impact of the COVID-19 pandemic on longitudinal trends of surgical mortality and inpatient quality of care in Ontario, Canada.

AIMS: Previous studies have shown the COVID-19 pandemic was associated with reductions in volume across a spectrum of non-SARS-CoV-2 hospitalizations. In the present study, we examine the impact of the pandemic on patient safety and quality of care. DESIGN: This is a retrospective population-based study of discharge abstracts. METHODS: We applied a set of nationally validated indicators for measuring the quality of inpatient care to hospitalizations in Ontario, Canada between January 2010 and December 2022. We measured 90-day mortality after selected types of higher risk admissions (such as cancer surgery and cardiovascular emergency) and the rate of patient harm events (such as delirium, pressure injuries and hospital-acquired infections) occurring during the hospital stay. RESULTS: A total 13,876,377 hospitalization episodes were captured. Compared with the pre-pandemic period, and independent of SARS-CoV-2 infection, the pandemic period was associated with higher rates of mortality after bladder cancer resection (adjusted risk ratio [aRR] 1.20 (1.07-1.34)) and open repair for abdominal aortic aneurysm (aRR 1.45 (1.06-1.99)). The pandemic was also associated with higher rates of delirium (adjusted odds ratio [aOR] 1.04 (1.02-1.06)), venous thromboembolism (aOR 1.10 (1.06-1.13)), pressure injuries (aOR 1.28 (1.24-1.33)), aspiration pneumonitis (aOR 1.15 (1.12-1.18)), urinary tract infections (aOR 1.02 (1.01-1.04)), Clostridiodes difficile infection (aOR 1.05 (1.02-1.09)), pneumothorax (aOR 1.08 (1.03-1.13)), and use of restraints (aOR 1.12 (1.10-1.14)), but was associated with lower rates of viral gastroenteritis (aOR 0.22 (0.18-0.28)). During the pandemic, SARS-CoV-2-positive admissions were associated with a higher likelihood of various harm events. CONCLUSION: The COVID-19 pandemic was associated with higher rates of patient harm for a wide range of non-SARS-CoV-2 inpatient populations. IMPACT: Understanding which quality measures are improving or deteriorating can help health systems prioritize quality improvement initiatives. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

SARS-CoV-2 infection among physicians over time in Ontario, Canada: a population-based retrospective cohort study.

AIM: To assess this risk of SARS-CoV-2 infection among Ontario physicians by specialty and in comparison with non-physician controls during the COVID-19 pandemic. METHODS: In this retrospective cohort study, the primary outcome was incident SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR). Secondary outcomes were hospitalization, use of critical care, and mortality. RESULTS: From March 1, 2020 to December 31, 2022, 6172/30 617 (20%) active Ontario physicians tested positive for SARS-CoV-2. Infection was less likely if physicians were older (OR 0.78 [0.76-0.81] per 10 years), rural residents (OR 0.70 [0.59-0.83]), and lived in more marginalized neighborhoods (OR 0.74 [0.62-0.89]), but more likely if they were female (OR 1.14 [1.07-1.22]), worked in long-term care settings (OR 1.16 [1.02-1.32]), had higher patient volumes (OR 2.05 [1.82-2.30] for highest vs lowest), and were pediatricians (OR 1.25 [1.09-1.44]). Compared with community-matched controls (n=29 763), physicians had a higher risk of infection during the first two waves of the pandemic (OR 1.38 [1.20-1.59]) but by wave 3 the risk was no longer significantly different (OR 0.93 [0.83-1.05]). Physicians were less likely to be hospitalized within 14 days of their first positive PCR test than non-physicians (P<0.0001), but there was no difference in the use of critical care (P=0.48) or mortality (P=0.15). CONCLUSION: Physicians had higher rates of infection than community-matched controls during the first two waves of the pandemic in Ontario, but not from wave 3 onward. Physicians practicing in long-term care facilities and pediatricians were more likely to test positive for SARS-CoV-2 than other physicians.

Estimating the incidence of breast cancer recurrence using administrative data.

BACKGROUND: Breast cancer is the most common cancer among women, but most cancer registries do not capture recurrences. We estimated the incidence of local, regional, and distant recurrences using administrative data. METHODS: Patients diagnosed with stage I-III primary breast cancer in Ontario, Canada from 2013 to 2017 were included. Patients were followed until 31/Dec/2021, death, or a new primary cancer diagnosis. We used hospital administrative data (diagnostic and intervention codes) to identify local recurrence, regional recurrence, and distant metastasis after primary diagnosis. We used logistic regression to explore factors associated with developing a distant metastasis. RESULTS: With a median follow-up 67 months, 5,431/45,857 (11.8%) of patients developed a distant metastasis a median 23 (9, 42) months after diagnosis of the primary tumor. 1086 (2.4%) and 1069 (2.3%) patients developed an isolated regional or a local recurrence, respectively. Patients with distant metastatic disease had a median overall survival of 15.4 months (95% CI 14.4-16.4 months) from the time recurrence/metastasis was identified. In contrast, the median survival for all other patients was not reached. Patients were more likely to develop a distant metastasis if they had more advanced stage, greater comorbidity, and presented with symptoms (p < 0.0001). Trastuzumab halved the risk of recurrence [OR 0.53 (0.45-0.63), p < 0.0001]. CONCLUSION: Distant metastasis is not a rare outcome for patients diagnosed with breast cancer, translating to an annual incidence of 2132 new cases (17.8% of all breast cancer diagnoses). Overall survival remains high for patients with locoregional recurrences, but was poor following a diagnosis of a distant metastasis.

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Development of population-level colon cancer pathway concordance measures and association with survival.

Clinical cancer pathways help standardize healthcare delivery to optimize patient outcomes and health system costs. However, population-level measurement of concordance between standardized pathways and actual care received is lacking. Two measures of pathway concordance were developed for a simplified colon cancer pathway map for Stage II-III colon cancer patients in Ontario, Canada: a cumulative count of concordant events (CCCE) and the Levenshtein algorithm. Associations of concordance with patient survival were estimated using Cox proportional hazards models adjusted for patient characteristics and time-dependent cancer-related activities. Models were compared and the impact of including concordance scores was quantified using the likelihood ratio chi-squared test. The ability of the measures to discriminate between survivors and decedents was compared using the C-index. Normalized concordance scores were significantly associated with patient survival in models for cancer stage-a 10% increase in concordance for Stage II patients resulted in a CCCE score adjusted hazard ratio (aHR) of death of 0.93, 95% CI 0.88-0.98 and a Levenshtein score aHR of 0.64, 95% CI 0.60-0.67. A similar relationship was found for Stage III patients-a 10% increase in concordance resulted in a CCCE aHR of 0.85, 95% CI 0.81-0.88 and a Levenshtein aHR of 0.78, 95% CI, 0.74-0.81. Pathway concordance can be used as a tool for health systems to monitor deviations from established clinical pathways. The Levenshtein score better characterized differences between actual care and clinical pathways in a population, was more strongly associated with survival and demonstrated better patient discrimination.

Erythroblastic oncogene B-2 status and intracranial metastatic disease in patients with gastrointestinal cancer: a systematic review.

PURPOSE: The incidence of intracranial metastatic disease (IMD) in patients with gastrointestinal (GI) cancers is rising. Expression of the erythroblastic oncogene B-2 (ERBB2) is associated with an in increased risk of IMD in patients with breast cancer. The implications of ERBB2 expression for IMD risk in patients with GI cancers is less clear. The objective of this systematic review was to determine the incidence of IMD and OS in patients with ERBB2+ gastrointestinal cancers. METHODS: A literature search of MEDLINE, EMBASE, CENTRAL, and grey literature sources was conducted from date of database inception to July 2021. Included studies reported outcomes on patients with IMD secondary to ERBB2 GI cancers. RESULTS: Fourteen cohort studies met inclusion criteria, of which thirteen were retrospective. Eleven studies reported on gastric, esophageal, or gastroesophageal junction cancers. Three studies directly compared incidence of IMD based on ERBB2 status and among these, ERBB2+ patients had a higher incidence of IMD. One study indicated that ERBB2+ patients had significantly longer OS from the times of primary cancer (P = .015) and IMD diagnosis (P = .01), compared with patients with ERBB2- disease. CONCLUSIONS: In this systematic review, patients with ERBB2+ GI cancer were more likely to develop IMD. Future study is required on the prognostic and predictive value of ERBB2 status in patients with GI cancers.

Inverse optimization on hierarchical networks: an application to breast cancer clinical pathways.

Clinical pathways are standardized processes that outline the steps required for managing a specific disease. However, patient pathways often deviate from clinical pathways. Measuring the concordance of patient pathways to clinical pathways is important for health system monitoring and informing quality improvement initiatives. In this paper, we develop an inverse optimization-based approach to measuring pathway concordance in breast cancer, a complex disease. We capture this complexity in a hierarchical network that models the patient's journey through the health system. A novel inverse shortest path model is formulated and solved on this hierarchical network to estimate arc costs, which are used to form a concordance metric to measure the distance between patient pathways and shortest paths (i.e., clinical pathways). Using real breast cancer patient data from Ontario, Canada, we demonstrate that our concordance metric has a statistically significant association with survival for all breast cancer patient subgroups. We also use it to quantify the extent of patient pathway discordances across all subgroups, finding that patients undertaking additional clinical activities constitute the primary driver of discordance in the population.

Multiple imputation and clinico-serological models to predict human papillomavirus status in oropharyngeal carcinoma: An alternative when tissue is unavailable.

In cancer epidemiological studies, determination of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) typically depends on the availability of tumor tissue testing, and/or tumor tissue access. Identifying alternative methods for estimating HPV status can improve the quality of such studies when tissue is unavailable. We developed multiple predictive models for tumor HPV status and prognosis by combining both clinico-epidemiological variables and either serological multiplex assays of HPV or multiple imputation of HPV status (HPVmi ). Sensitivity, specificity and accuracy of these methods compared to either p16 immunostaining (p16 IHC) or survival were assessed. When compared to a reference of tumor tissue p16 IHC in 783 OPSCC patients, the clinic-HPVsero model incorporating a composite of 20 HPV serological antibodies (HPVsero ) and 4 clinical factors (c-index: 0.96) performed better than using HPVsero (c-index: 0.92) or HPVmi (c-index: 0.76) alone. However, the model that contained a single HPV16 E6 antibody combined with four clinical variables, performed extremely well (clinic-s1-16E6; c-index: 0.95). When defining HPV status by HPVsero , s1-16E6, HPVmi or through p16 IHC, each of these definitions demonstrated improved overall and disease-free survival in HPV-positive OPSCC patients, when compared to HPV-negative patients (adjusted hazard ratios between 0.25 and 0.63). Our study demonstrates that when blood samples are available, a model that utilizes a single s1-16E6 antibody combined with several clinical features has excellent test performance characteristics to estimate HPV status and prognosis. When neither blood nor tumor tissue is available, multiple imputation, calibrated on local population characteristics, remains a viable, but suboptimal option.

Evaluating multiple living kidney donor candidates simultaneously is more cost-effective than sequentially.

When multiple living donor candidates come forward to donate a kidney to the same recipient, some living donor programs evaluate one candidate at a time to avoid unnecessary evaluations. Evaluating multiple candidates concurrently rather than sequentially may be cost-effective from a societal perspective if it reduces the time recipients spend on dialysis. We used a simple decision tree to estimate the cost-effectiveness of evaluating two to four candidates simultaneously rather than sequentially as potential kidney donors for the same intended recipient. Evaluating two donor candidates simultaneously cost $1,266 (CAD) more than if they were evaluated sequentially, but living donation occurred one month earlier. This translated into $6,931 in averted dialysis costs and a total cost-savings of $5,665 per intended recipient. Simultaneous evaluations also resulted in one percent more living donor transplants and overall gains in quality-of-life as recipients spent less time on dialysis. If recipients were free from dialysis at the start of donor candidate evaluations, simultaneous evaluations also reduced the rate of dialysis initiation by two percent. Benefits were also observed in the three- and four-candidate scenarios. Thus, living donor programs should consider evaluating up to four living donor candidates simultaneously when they come forward for the same recipient as health care system costs incurred are more than offset by avoided dialysis costs.

Human papillomavirus and p16 immunostaining, prevalence and prognosis of squamous carcinoma of unknown primary in the head and neck region.

The prevalence of human papillomavirus (HPV) in squamous cell carcinoma of unknown primary in the head and neck (SCCUPHN), and prognosis by HPV status of SCCUPHN patients has been difficult to estimate because of the rarity of this subtype. In MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, EMBASE, Cochrane library and Web of Science searches, observational studies and clinical trials that reported survival rates of patients with SCCUPHN by HPV status were identified. Meta-analysis estimated the prevalence and prognosis (overall survival, OS; progression-free survival, PFS) of SCCUPHN by HPV status, and compared them to studies of oropharyngeal squamous cell carcinoma (OPSCC) from the same institutions and across continents. In 17 SCCUPHN studies (n = 1,149) and 17 institution-matched OPSCC studies (n = 6,522), the pooled HPV prevalence of SCCUPHN was 49%, which was only 10% (95%CI: 1-19%) lower than OPSCC prevalence in the underlying population. Estimated 5-year OS for HPV-negative SCCUPHN was 44% (95%CI: 36-51%) vs. HPV-positive SCCUPHN of 91% (95%CI: 86-96%); hazard ratio (HR) for OS was 3.25 (95%CI: 2.45-4.31) and PFS was 4.49 (95%CI: 2.88-7.02). HRs by HPV status for OPSCC were similar to that in SCCUPHN. While North American SCCUPHNs had higher HPV prevalence than European SCCUPHNs (OR = 2.68 (95%CI: 1.3-5.6)), HR of OS for HPV-negative vs. HPV-positive patients were similar in both continents (HRs of 3.78-4.09). Prevalence of HPV among SCCUPHN patients were lower than in OPSCC. The survival benefit conferred by being HPV-positive was similar in SCCUPHN as in OPSCCs, independent of continent.

Potential implications of a more timely living kidney donor evaluation.

Living donor kidney transplantation is the most promising way to avoid or minimize the amount of time a recipient spends on dialysis before transplantation. We studied 887 living kidney donors at 5 transplant centers in Ontario, Canada, who started their evaluation and donated between April 2006 and March 2014. Using a series of hypothetical scenarios, we estimated the impact of an earlier living donor evaluation completion and donation on the number pre-emptive transplants, the time spent on dialysis, healthcare cost savings from averted dialysis costs (CAD $2016), and the number of additional transplants. During the study period, if the donor transplants occurred 3 months earlier, the healthcare system would save on average $12 055 (standard deviation [SD] $13 594) per recipient; 21 recipients could have avoided dialysis altogether, and 57 additional transplants (a 26% increase) could have occurred each year. For the 220 living kidney donor transplants performed in Ontario, Canada, each year, this translates to a total annual cost savings of $2.7M. In conclusion, a more timely evaluation of living donor candidates and their intended recipients may increase the supply of kidneys for transplantation. Improved evaluation efficiency may also yield more pre-emptive transplants and substantial healthcare cost savings through averted dialysis costs.

Gestational hypertension and preeclampsia in living kidney donors.

BACKGROUND: Young women wishing to become living kidney donors frequently ask whether nephrectomy will affect their future pregnancies. METHODS: We conducted a retrospective cohort study of living kidney donors involving 85 women (131 pregnancies after cohort entry) who were matched in a 1:6 ratio with 510 healthy nondonors from the general population (788 pregnancies after cohort entry). Kidney donations occurred between 1992 and 2009 in Ontario, Canada, with follow-up through linked health care databases until March 2013. Donors and nondonors were matched with respect to age, year of cohort entry, residency (urban or rural), income, number of pregnancies before cohort entry, and the time to the first pregnancy after cohort entry. The primary outcome was a hospital diagnosis of gestational hypertension or preeclampsia. Secondary outcomes were each component of the primary outcome examined separately and other maternal and fetal outcomes. RESULTS: Gestational hypertension or preeclampsia was more common among living kidney donors than among nondonors (occurring in 15 of 131 pregnancies [11%] vs. 38 of 788 pregnancies [5%]; odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P=0.01). Each component of the primary outcome was also more common among donors (odds ratio, 2.5 for gestational hypertension and 2.4 for preeclampsia). There were no significant differences between donors and nondonors with respect to rates of preterm birth (8% and 7%, respectively) or low birth weight (6% and 4%, respectively). There were no reports of maternal death, stillbirth, or neonatal death among the donors. Most women had uncomplicated pregnancies after donation. CONCLUSIONS: Gestational hypertension or preeclampsia was more likely to be diagnosed in kidney donors than in matched nondonors with similar indicators of baseline health. (Funded by the Canadian Institutes of Health Research and others.).

Duration of Living Kidney Transplant Donor Evaluations: Findings From 2 Multicenter Cohort Studies.

BACKGROUND: A prolonged living kidney donor evaluation may result in worse outcomes for transplant recipients. Better knowledge of the duration of this process may help inform future donors and identify opportunities for improvement. STUDY DESIGN: 1 prospective and 1 retrospective cohort study. SETTING & PARTICIPANTS: At 16 Canadian and Australian transplantation centers (prospective cohort) and 5 Ontario transplantation centers (retrospective cohort), we assessed the duration of living kidney donor evaluation and explored donor, recipient, and transplantation factors associated with longer evaluation times. Data were obtained from 2 sources: donor medical records using chart abstraction and health care administrative databases. PREDICTORS: Donor and recipient demographics, direct versus paired donation, center-level variables. OUTCOMES: Duration of living donor evaluation. RESULTS: The median total duration of transplantation evaluation (time from when the candidate started the evaluation until donation) was 10.3 (IQR, 6.5-16.7) months. The median duration from evaluation start until approval to donate was 7.9 (IQR, 4.6-14.1) months, and from approval until donation was 0.7 (IQR, 0.3-2.4) months, respectively. The median time between the first and last consultation among donors who completed a nephrology, surgery, and psychosocial assessment in the prospective cohort was 3.0 (IQR, 1.0-6.3) months, and between computed tomography angiography and donation was 4.8 (IQR, 2.6-9.2) months. After adjustment, the total duration of transplantation evaluation was longer if the donor participated in paired donation (6.6 [95% CI, 1.6-9.7] months) and if the recipient was referred later relative to the donor's evaluation start date (0.9 [95% CI, 0.8-1.0] months [per month of delayed referral]). Results depended on whether the recipient was receiving dialysis. LIMITATIONS: Living donor candidates who did not donate were not included and proxy measures were used for some dates in the donor evaluation process. CONCLUSIONS: The duration of kidney transplant donor evaluation is variable and can be lengthy. Better understanding of the reasons for a prolonged evaluation may inform quality improvement initiatives to reduce unnecessary delays.

Cost-Effectiveness of First-Line Sevelamer and Lanthanum versus Calcium-Based Binders for Hyperphosphatemia of Chronic Kidney Disease.

BACKGROUND: Phosphate binders are used to treat hyperphosphatemia among patients with chronic kidney disease (CKD). OBJECTIVES: To conduct an economic evaluation comparing calcium-free binders sevelamer and lanthanum with calcium-based binders for patients with CKD. METHODS: Effectiveness data were obtained from a recent meta-analysis of randomized trials. Effectiveness was measured as life-years gained and translated to quality-adjusted life-years (QALYs) using utility weights from the literature. A Markov model consisting of non-dialysis-dependent (NDD)-CKD, dialysis-dependent (DD)-CKD, and death was developed to estimate the incremental costs and effects of sevelamer and lanthanum versus those of calcium-based binders. A lifetime horizon was used and both costs and effects were discounted at 1.5%. All costs are presented in 2015 Canadian dollars from the Canadian public payer perspective. Results of probabilistic sensitivity analysis were presented using cost-effectiveness acceptability curves. Sensitivity analyses were conducted for risk pooling methods, omission of dialysis costs, and persistence of drug effects on mortality. RESULTS: Sevelamer resulted in an incremental cost-effectiveness ratio of $106,522/QALY for NDD-CKD and $133,847/QALY for DD-CKD cohorts. Excluding dialysis costs, sevelamer was cost-effective in the NDD-CKD cohort ($5,847/QALY) and the DD-CKD cohort ($11,178/QALY). Lanthanum was dominated regardless of whether dialysis costs were included. CONCLUSIONS: Existing evidence does not clearly support the cost-effectiveness of non-calcium-containing phosphate binders (sevelamer and lanthanum) relative to calcium-containing phosphate binders in DD-CKD patients. Our study suggests that sevelamer may be cost-effective before dialysis onset. Because of the remaining uncertainty in several clinically relevant outcomes over time in DD-CKD and NDD-CKD patients, further research is encouraged.

The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis.

Background: It remains unclear which phosphate binders should be preferred for hyperphosphatemia management in chronic kidney disease (CKD). Methods: We performed a systematic review and meta-analysis of randomized trials comparing sevelamer or lanthanum with other phosphate binders in CKD. Results: Fifty-one trials (8829 patients) were reviewed. Compared with calcium-based binders, all-cause mortality was nonsignificantly lower with sevelamer {risk ratio [RR] 0.62 [95% confidence interval (CI) 0.35-1.08]} and lanthanum [RR 0.73 (95% CI 0.18-3.00)], but risk of bias was concerning. Compared with calcium-based binders, sevelamer reduced the risk of hypercalcemia [RR 0.27 (95% CI 0.17-0.42)], as did lanthanum [RR 0.12 (95% CI 0.05-0.32)]. Sevelamer reduced hospitalizations [RR 0.50 (95% CI 0.31-0.81)], but not lanthanum [RR 0.80 (95% CI 0.34-1.93)]. The presence/absence of other clinically relevant outcomes was infrequently reported. Compared with calcium-based binders, sevelamer reduced serum calcium, low-density lipoprotein and coronary artery calcification, but increased intact parathyroid hormone. The clinical relevance of these changes is unknown since corresponding clinical outcomes were not reported. Lanthanum had less favorable impact on biochemical parameters. Sevelamer hydrochloride and sevelamer carbonate were similar in three studies. Sevelamer was similar to lanthanum (three studies) and iron-based binders (three studies). Conclusion: Sevelamer was associated with a nonsignificant reduction in mortality and significantly lower hospitalization rates and hypercalcemia compared with calcium-based binders. However, differences in important outcomes, such as cardiac events, fractures, calciphylaxis, hyperchloremic acidosis and health-related quality of life remain understudied. Lanthanum and iron-based binders did not show superiority for any clinically relevant outcomes. Future studies that fail to measure clinically important outcomes (the reason why phosphate binders are prescribed in the first place) will be wasteful.

Human papillomavirus in oropharyngeal cancer in Canada: analysis of 5 comprehensive cancer centres using multiple imputation.

BACKGROUND: The incidence of oropharyngeal cancer has risen over the past 2 decades. This rise has been attributed to human papillomavirus (HPV), but information on temporal trends in incidence of HPV-associated cancers across Canada is limited. METHODS: We collected social, clinical and demographic characteristics and p16 protein status (p16-positive or p16-negative, using this immunohistochemistry variable as a surrogate marker of HPV status) for 3643 patients with oropharyngeal cancer diagnosed between 2000 and 2012 at comprehensive cancer centres in British Columbia (6 centres), Edmonton, Calgary, Toronto and Halifax. We used receiver operating characteristic curves and multiple imputation to estimate the p16 status for missing values. We chose a best-imputation probability cut point on the basis of accuracy in samples with known p16 status and through an independent relation between p16 status and overall survival. We used logistic and Cox proportional hazard regression. RESULTS: We found no temporal changes in p16-positive status initially, but there was significant selection bias, with p16 testing significantly more likely to be performed in males, lifetime never-smokers, patients with tonsillar or base-of-tongue tumours and those with nodal involvement (p < 0.05 for each variable). We used the following variables associated with p16-positive status for multiple imputation: male sex, tonsillar or base-of-tongue tumours, smaller tumours, nodal involvement, less smoking and lower alcohol consumption (p < 0.05 for each variable). Using sensitivity analyses, we showed that different imputation probability cut points for p16-positive status each identified a rise from 2000 to 2012, with the best-probability cut point identifying an increase from 47.3% in 2000 to 73.7% in 2012 (p < 0.001). INTERPRETATION: Across multiple centres in Canada, there was a steady rise in the proportion of oropharyngeal cancers attributable to HPV from 2000 to 2012.

A cost-effectiveness analysis of human papillomavirus vaccination of boys for the prevention of oropharyngeal cancer.

BACKGROUND: Many western countries have established female human papillomavirus (HPV) vaccination programs for the prevention of cervical cancer. The quadrivalent HPV vaccine (HPV4) has proven efficacy against additional HPV-related disease in both sexes, but the cost effectiveness of male HPV vaccination remains controversial. To assess the cost effectiveness of male HPV vaccination in Canada with respect to oropharyngeal cancer (OPC), the authors performed a preliminary cost-effectiveness analysis. METHODS: After an extensive literature review regarding HPV-related OPC in Canadian males, health care costs and clinical effectiveness estimates were obtained. A Markov model was used to compare the potential costs and effectiveness of HPV4 versus no vaccination among boys aged 12 years. A theoretical cohort based on a Canadian population of 192,940 boys aged 12 years in 2012 was assumed to apply the model. A 3-month cycle length was used with a "lifetime" time horizon. The outcome of the analysis was the incremental cost per quality-adjusted life-year (QALY). Sensitivity analyses were conducted on variables, including the vaccine uptake rate and vaccine efficacy. RESULTS: Assuming 99% vaccine efficacy and 70% uptake, HPV4 produced 0.05 more QALYs and saved $145 Canadian dollars (CAD) per individual compared with no vaccine (QALYs and costs were discounted at 5% per year). Assuming 50% vaccine efficacy and 50% uptake, HPV4 produced 0.023 more QALYs and saved $42 CAD. The results indicated that HPV4 in males may potentially save between $8 and $28 million CAD for the theoretical cohort of 192,940 over its lifetime. CONCLUSIONS: On the basis of this model, HPV vaccination for boys aged 12 years may be a cost-effective strategy for the prevention of OPC in Canada.