Abstract
Background
Suicide is among the top 10 leading causes of premature morality in the United States and its rates continue to increase. Thus, its prevention has become a salient public health ...responsibility. Risk factors of suicide transcend the individual and societal level as risk can increase based on climatic variables. The purpose of the present study is to evaluate the association between average temperature and suicide rates in the five most populous counties in California using mortality data from 1999 to 2019.
Methods
Monthly counts of death by suicide for the five counties of interest were obtained from CDC WONDER. Monthly average, maximum, and minimum temperature were obtained from nCLIMDIV for the same time period. We modelled the association of each temperature variable with suicide rate using negative binomial generalized additive models accounting for the county-specific annual trend and monthly seasonality.
Results
There were over 38,000 deaths by suicide in California’s five most populous counties between 1999 and 2019. An increase in average temperature of 1 °C corresponded to a 0.82% increase in suicide rate (IRR = 1.0082 per °C; 95% CI = 1.0025–1.0140). Estimated coefficients for maximum temperature (IRR = 1.0069 per °C; 95% CI = 1.0021–1.0117) and minimum temperature (IRR = 1.0088 per °C; 95% CI = 1.0023–1.0153) were similar.
Conclusion
This study adds to a growing body of evidence supporting a causal effect of elevated temperature on suicide. Further investigation into environmental causes of suicide, as well as the biological and societal contexts mediating these relationships, is critical for the development and implementation of new public health interventions to reduce the incidence of suicide, particularly in the face increasing temperatures due to climate change.
Background
In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab‐paclitaxel (GnP) have been publicly funded for first‐line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic ...pancreatic cancer (mPC) since April 2015. We examined the real‐world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC.
Methods
Patients receiving first‐line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database. Baseline characteristics and outcomes were obtained through the Ontario Cancer Registry and other population‐based databases. Overall survival (OS) was assessed using Kaplan‐Meier and weighted Cox proportional hazard models, weighted by the inverse propensity score adjusting for baseline characteristics. Weighted odds ratio (OR) for hospitalization and emergency department visits (EDV) were estimated from weighted logistic regression models.
Results
For 1130 patients (632 FFX, 498 GnP), crude median OS was 9.6 and 6.1 months for FFX and GnP, respectively. Weighted OS was improved for FFX vs GnP (HR = 0.77, 0.70‐0.85). Less frequent EDV and hospitalization were observed in FFX (EDV: 67.8%; Hospitalization: 49.2%) than GnP (EDV: 77.7%; Hospitalization: 59.3%). More frequent febrile neutropenia‐related hospitalization was observed in FFX (5.8%) than GnP (3.3%). Risk of EDV and hospitalization were significantly lower for FFX vs GnP (EDV: OR = 0.68, P = .0001; Hospitalization: OR = 0.76, P = .002), whereas the risk of febrile neutropenia‐related hospitalization was significantly higher (OR = 2.12, P = .001). Outcomes for uLAPC and mPC were similar.
Conclusion
In the real world, FFX had longer OS, less frequent all‐cause EDV and all‐cause hospitalization, but more febrile neutropenia‐related hospitalization compared to GnP.
In the real world, implementation of universal public funding of FOLFIRINOX for metastatic pancreatic cancer was associated with improved overall survival, less frequent all‐cause emergency department visits, less frequent all‐cause hospitalization, but increased febrile neutropenia‐related hospitalization compared to patients treated with gemcitabine + nab‐paclitaxel. Expanding funding to include unresectable locally advanced pancreatic cancer was associated with a similar trend in benefits, but with improved absolute survival.
Objective: Various statistical methods have been developed to estimate hazard ratios (HRs) from published Kaplan-Meier (KM) curves for the purpose of performing meta-analyses. The objective of this ...study was to determine the reliability, accuracy, and precision of four commonly used methods by Guyot, Williamson, Parmar, and Hoyle and Henley. Design: Pivotal randomized controlled trials (RCTs) in oncology were identified from the pan-Canadian Oncology Drug Review (pCODR) database (primary analysis) and the Food and Drug Administration's (FDA) drug approvals page (secondary analysis) between January 2012 and May 2016. Two reviewers independently reconstructed HRs using each method on KM curves extracted from each trial and compared them with reported HRs (gold standard). Bland-Altman plots and summary statistics were calculated to assess accuracy and precision of these methods. Interrater reliability was assessed using intraclass correlation coefficient (ICC). These four methods were also applied to KM curves of different structures (ie, flat versus steep curves). Results: A total of 118 KM curves (55 RCTs) and 77 KM curves (46 RCTs) were extracted from pCODR and FDA, respectively. In the primary analysis, the Guyot method was the most accurate with the lowest mean error (0.0094; 95% CI, -0.0012-0.020). All four methods had excellent interrater reliability. The Guyot method showed the smallest bias and greatest precision on the Bland-Altman plots. The Guyot method was consistently superior in both the secondary and all sensitivity analyses. Conclusion: In the absence of reported HRs, we recommend that researchers consider the Guyot method to reconstruct HRs from KM curves when performing aggregate data meta-analyses.
We evaluated outcomes in non-small cell lung cancer (NSCLC) patients who presented with brain-only metastatic (BOM) disease overall and by EGFR/ALK mutation status.
We analyzed clinico-demographic, ...treatment and survival data for all NSCLC patients who presented to our center between 2014 and 2016 with BOM as their first presentation of metastatic disease. Differences in overall survival (OS) were evaluated using log-rank tests for NSCLC wildtype (NSCLCwt) versus NSCLC with an ALK-rearrangement/EGFR-mutation (NSCLCmut+).
Of 109 patients with BOM, median age was 68 years; 51 % were female; 69 % Caucasian; 76 % ever-smoker; 76 % adenocarcinoma; and 25 % NSCLCmut+. While 41 patients (38 %) had subsequent brain-only progressive disease (PD), 22 (20 %) developed extracranial metastases. A higher proportion of NSCLCmut+ (vs –wt) subsequently progressed outside the brain (37 % vs 15 %, p = 0.03). Median time-to-first-extracranial-metastases was 8.5 (NSCLCmut+) vs 21.0 months (NSCLCwt; p = 0.23).
With 17.7 months median follow-up, median-OS was 15.9 months 95%CI: 11.5–21.3; all patients; 12.3 7.4–18.4; NSCLCwt and 38.9 21.3-not reached (NR); NSCLCmut+ (p = 0.09). In 33 of 80 patients with de novo BOM, the primary tumor was treated with surgery or radiotherapy. In patients with NSCLCwt, there was no OS benefit associated with local lung tumor treatment (p = 0.68), whereas in NSCLCmut + pts, local lung tumor treatment correlated with greater OS (median-OS NR vs 21.5 months; p = 0.05).
In patients with NSCLCwt with BOM, we observed a -predominant pattern of brain-only secondary progression, however patients with NSCLCmut + more often progressed extracranially. In patients with NSCLCmut+ and BOM, definitive primary tumor treatment correlated with improved survival.
•We observed favourable outcomes in patients with NSCLC and brain only metastatic disease.•Significant differences in metastatic failure patterns according to mutational status were seen.•Primary tumor treatment was associated with improved survival in patients with NSCLCmut+.
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Introduction
The American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) have been developed to ...quantify clinical benefit and establish value of anticancer therapies. While ASCO-VF is indifferent to the cancer type, ESMO-MCBS does not endorse their framework for scoring hematologic malignancies. The reason for this exclusion and whether ESMO-MCBS can be applied in the hematologic setting is still unclear. The purpose of this study was to determine whether measurement characteristics of ESMO-MCBS are similar to ASCO-VF when evaluating hematologic malignancies.
Methods
Phase III randomized controlled trials (RCTs) of hematological malignancy drugs approved by the US Food and Drug Administration, European Medicines Agency and Health Canada between 2006 to 2017 were identified and scored using ASCO-VF (version 2) and ESMO-MCBS (version 1.1) by two independent reviewers. We assessed the convergent construct validity of the two frameworks to determine the degree to which these two theoretically similar measures assess the same construct of clinical benefit. Spearman correlation coefficients were calculated for the preliminary framework scores (using only the survival efficacy components of the scores) and the final framework scores (following adjustment of the preliminary scores with toxicity and quality of life (QoL) data). Correlation coefficients were also calculated for each subtype of blood cancer separately. The inter-rater reliability of the frameworks was assessed using intra-class correlation coefficients (ICC).
Results
In total, 48 studies were included and scored using the ASCO-VF (median score: 34.38; IQR: 22.26 - 51.69) and ESMO-MCBS (median score: 3; IQR: 2.75 - 4). Out of the 48 RCTs, 16 (33%) evaluated novel anticancer treatments for leukemia, 23 (48%) for myeloma, 8 (17%) for lymphoma and 1 (2%) for myelodysplastic syndromes. Spearman correlation coefficients between both frameworks for preliminary and final scores were 0.01 (95% CI, -0.23 to 0.25) and -0.02 (95% CI, -0.28 to 0.24), respectively. When stratified by indication, the correlation coefficients for the preliminary scores were -0.01 (95% CI, -0.50 to 0.49), -0.06 (95% CI, -0.46 to 0.29), and 0.58 (95% CI, -0.21 to 0.91) for leukemia, myeloma, and lymphoma, respectively. The correlation coefficients for the final scores by cancer indications were -0.09 (95% CI, -0.56 to 0.42), 0.15 (95% CI, -0.22 to 0.49), and -0.29 (95% CI, -0.86 to 0.52) for leukemia, myeloma, and lymphoma, respectively (Table 1). For both preliminary and final scores, ASCO-VF showed excellent and ESMO-MCBS showed good inter-rater reliability (Table 2).
Conclusions
Our results suggest divergent validity of ESMO-MCBS and ASCO-VF when assessing hematologic malignancies, indicating that these frameworks likely measure different constructs of clinical benefit in this setting. Furthermore, the ASCO-VF demonstrated improved inter-rater reliability compared to ESMO-MCBS. It remains unclear which framework is correctly assessing the clinical benefit of hematologic drugs. To better understand if one framework is more accurate in its evaluation, future research that compares these frameworks to other established measures of clinical benefit (such as quality adjusted life years) in the hematologic setting is warranted. Due to the lack of construct validity and ESMO's endorsement of their framework solely for solid cancers, the ASCO-VF should currently be considered for use in the hematologic setting.
No relevant conflicts of interest to declare.
Purpose Whether the ASCO Value Framework and the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) measure similar constructs of clinical benefit is unclear. It ...is also unclear how they relate to quality-adjusted life-years (QALYs) and funding recommendations in the United Kingdom and Canada. Methods Randomized clinical trials of oncology drug approvals by the US Food and Drug Administration, European Medicines Agency, and Health Canada between 2006 and August 2015 were identified and scored using the ASCO version 1 (v1) framework, ASCO version 2 (v2) framework, and ESMO-MCBS by at least two independent reviewers. Spearman correlation coefficients were calculated to assess construct (between frameworks) and criterion validity (against QALYs from the National Institute for Health and Care Excellence NICE and the pan-Canadian Oncology Drug Review pCODR). Associations between scores and NICE/pCODR recommendations were examined. Inter-rater reliability was assessed using intraclass correlation coefficients. Results From 109 included randomized clinical trials, 108 ASCOv1, 111 ASCOv2, and 83 ESMO scores were determined. Correlation coefficients for ASCOv1 versus ESMO, ASCOv2 versus ESMO, and ASCOv1 versus ASCOv2 were 0.36 (95% CI, 0.15 to 0.54), 0.17 (95% CI, -0.06 to 0.37), and 0.50 (95% CI, 0.35 to 0.63), respectively. Compared with NICE QALYs, correlation coefficients were 0.45 (ASCOv1), 0.53 (ASCOv2), and 0.46 (ESMO); with pCODR QALYs, coefficients were 0.19 (ASCOv1), 0.20 (ASCOv2), and 0.36 (ESMO). None of the frameworks were significantly associated with NICE/pCODR recommendations. Inter-rater reliability was good for all frameworks. Conclusion The weak-to-moderate correlations of the ASCO frameworks with the ESMO-MCBS, as well as their correlations with QALYs and with NICE/pCODR funding recommendations, suggest different constructs of clinical benefit measured. Construct convergent validity with the ESMO-MCBS did not increase with the updated ASCO framework.
Studies to date have yielded inconclusive results as to whether maternal medical history during pregnancy, and a child's early-life medical history contribute to the development of childhood brain ...tumours (CBTs). This study examined associations between maternal and childhood medical history and the risk of CBTs.
The Childhood Brain Tumour Epidemiology Study of Ontario (CBREO) examined children 0-15 years of age with newly diagnosed CBTs from 1997 to 2003. Multivariable logistic regression analysis determined associations for prenatal medications and childhood medical history, adjusted for child's demographics, and maternal education. Analyses were stratified by histology. A latency period analysis was conducted using 12- and 24-month lead times.
Maternal intake of immunosuppressants during the prenatal period was significantly associated with glial tumours (OR 2.73, 95% CI 1.17-6.39). Childhood intake of anti-epileptics was significantly associated with CBTs overall, after accounting for 12-month (OR 8.51, 95% CI 3.35-21.63) and 24-month (OR 6.04, 95% CI 2.06-17.70) lead time before diagnosis. No associations for other medications were found.
This study underscores the need to examine potential carcinogenic effects of the medication classes highlighted and of the indication of medication use. Despite possible reverse causality, increased CBT surveillance for children with epilepsy might be warranted.
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