ABSTRACT
Background: Studies show that more than 5.1 million deaths annually are attributed to nonoptimal temperatures, including extreme cold and extreme heat. However, those studies mostly report average estimates across large geographical areas. The health risks attributed to nonoptimal temperatures in British Columbia (BC) are reported incompletely or limit the study area to urban centers. In this study, we aim to estimate the attributable deaths linked to nonoptimal temperatures in all five regional health authorities (RHAs) of BC from 2001 to 2021. Methods: We applied the widely used distributed lag nonlinear modeling approach to estimate temperature-mortality association in the RHAs of BC, using daily all-cause deaths and 1 × 1 km gridded daily mean temperature. We evaluated the model by comparing the model-estimated attributable number of deaths during the 2021 heat dome to the number of heat-related deaths confirmed by the British Columbia Coroners Service. Results: Overall, between 2001 and 2021, we estimate that 7.17% (95% empirical confidence interval = 3.15, 10.32) of deaths in BC were attributed to nonoptimal temperatures, the majority of which are attributed to cold. On average, the mortality rates attributable to moderate cold, moderate heat, extreme cold, and extreme heat were 47.04 (95% confidence interval [CI] = 45.83, 48.26), 0.94 (95% CI = 0.81, 1.08), 2.88 (95% CI = 2.05, 3.71), and 3.10 (95% CI = 1.79, 4.4) per 100,000 population per year, respectively. Conclusions: Our results show significant spatial variability in deaths attributable to nonoptimal temperatures across BC. We find that the effect of extreme temperatures is significantly less compared to milder nonoptimal temperatures between 2001 and 2021. However, the increased contribution of extreme heat cannot be ruled out in the near future.
ABSTRACT
BACKGROUND: Congenital anomalies (CA) are one of the leading causes of infant mortality and long-term disability. Many jurisdictions rely on health administrative data to monitor these conditions. Case definition algorithms can be used to monitor CA; however, validation of these algorithms is needed to understand the strengths and limitations of the data. This study aimed to validate case definition algorithms used in a CA surveillance system in British Columbia (BC), Canada. METHODS: A cohort of births between March 2000 and April 2002 in BC was linked to the Health Status Registry (HSR) and the BC Congenital Anomalies Surveillance System (BCCASS) to identify cases and non-cases of specific anomalies within each surveillance system. Measures of algorithm performance were calculated for each CA using the HSR as the reference standard. Agreement between both databases was calculated using kappa coefficient. The modified Standards for Reporting Diagnostic Accuracy guidelines were used to enhance the quality of the study. RESULTS: Measures of algorithm performance varied by condition. Positive predictive value (PPV) ranged between approximately 73%-100%. Sensitivity was lower than PPV for most conditions. Internal congenital anomalies or conditions not easily identifiable at birth had the lowest sensitivity. Specificity and negative predictive value exceeded 99% for all algorithms. CONCLUSION: Case definition algorithms may be used to monitor CA at the population level. Accuracy of algorithms is higher for conditions that are easily identified at birth. Jurisdictions with similar administrative data may benefit from using validated case definitions for CA surveillance as this facilitates cross-jurisdictional comparison.
Subject(s)
Algorithms , Infant , Infant, Newborn , Humans , Predictive Value of Tests , Canada/epidemiology , Reference Standards , Databases, FactualABSTRACT
SETTING: Congenital anomalies (CAs) can cause lifelong morbidity and accounted for 23.2% of infant deaths from 2003 to 2007. In British Columbia (BC), surveillance of CAs has been irregular since the early 2000s. To enhance CAs surveillance in BC, the Public Health Agency of Canada has provided funding for the implementation of the BC Congenital Anomalies Surveillance System (BCCASS). INTERVENTION: BCCASS is a population-based surveillance system. The system leverages existing administrative data sources that capture information regarding vital events, disease status, drug prescription, and healthcare utilization. The system uses a series of algorithms to capture specific CAs diagnoses, some of which are further validated with the support of the Provincial Advisory Committee. This Advisory Committee is a multi-stakeholder coalition that includes the BC Office of the Provincial Health Officer, subject matter experts, data partners, users, and academia, and acts to provide support, expertise, and strategic guidance to BCCASS. OUTCOMES: Through BCCASS, prevalence and historical trends for 35 CAs in BC are available. Information pertaining to maternal place of residence, risk, and protective factors can be used for association studies such as links to environmental hazards and cluster analysis. IMPLICATIONS: BCCASS is a cost-effective and sustainable system that leverages existing data sources necessary to understand the overall burden of CAs across the BC population. This is fundamental to support data-driven decisions around policy development, program planning, and evaluation of preventive measures. Strong coalitions with stakeholders are instrumental to ensure successful implementation and expansion in the future.
RéSUME: CONTEXTE: Les anomalies congénitales (AC) peuvent causer une morbidité à vie et ont représenté 23,2 % des décès infantiles de 2003 à 2007. En Colombie-Britannique, la surveillance des AC a été irrégulière depuis le début des années 2000. Afin d'améliorer la surveillance de l'AC en Colombie-Britannique, l'Agence de la santé publique du Canada a financé la mise en Åuvre du BC Congenital Anomalies Surveillance System (BCCASS). INTERVENTION: Le BCCASS est un système de surveillance basé sur la population. Le système exploite les sources de données administratives existantes qui capturent des informations concernant les événements vitaux, les diagnostics médicaux, la prescription de médicaments et l'utilisation des soins de santé. Le système utilise une série d'algorithmes pour saisir des diagnostics d'AC spécifiques, dont certains sont ensuite validés avec le soutien du Comité consultatif provincial. Ce comité consultatif est une coalition multipartite entre le bureau de l'Agence de santé provincial de la Colombie-Britannique, des experts en la matière, des partenaires de données, des utilisateurs et des universitaires, qui agit pour fournir un soutien, une expertise et des conseils stratégiques au BCCASS. RéSULTATS: Par le BCCASS, la prévalence et les tendances historiques pour 35 AC en Colombie-Britannique sont disponibles. Les informations relatives au lieu de résidence de la mère, aux facteurs de risque et de protection peuvent être utilisées pour des études d'association telles que les liens avec les facteurs environnementaux et l'analyse typologique. INCIDENCES: Le BCCASS est un système rentable et durable qui tire parti des sources de données existantes nécessaires pour comprendre le fardeau global des CA dans l'ensemble de la population de la Colombie-Britannique. Ceci est fondamental pour soutenir les décisions fondées sur les données concernant l'élaboration de politiques, la planification de programmes et l'évaluation des mesures préventives. Des coalitions solides avec les parties prenantes sont essentielles pour assurer une mise en Åuvre et une expansion réussie dans l'avenir.
Subject(s)
Population Surveillance , Public Health , British Columbia/epidemiology , Humans , Infant , Prevalence , Program DevelopmentABSTRACT
Several epidemiological studies have found an association between maternal antibiotics use during pregnancy and increased risk of certain cancer types, although conclusions differ between studies. We examined this association in a cohort study including 262 116 mother-child pairs of Manitoba births between 1996 and 2013. Maternal antibiotics use during prepregnancy (6 months prior to pregnancy) and pregnancy periods was assessed. Children's cancer incidence was tracked up to the end of the follow-up period (December 2015). We calculated incidence rate and used Cox regression to estimate adjusted hazard ratios (HRs). Antibiotics use during pregnancy was not associated with overall cancer (HR = 1.1, 95% confidence interval 0.9-1.4), leukemias (1.3, 0.9-1.8), or acute lymphocytic leukemia (1.1, 0.7-1.6). The association between antibiotics use and overall cancer risk differed by trimester: 1.5 (1.1-1.9) in the first, 0.8 (0.6-1.0) in the second, and 1.1 (0.8-1.5) in the third trimester. Further research is necessary to confirm the association between first-trimester exposure and cancer risk after a better controlling of confounding factors.
Subject(s)
Anti-Bacterial Agents/adverse effects , Maternal Exposure/adverse effects , Neoplasms/epidemiology , Neoplasms/etiology , Prenatal Exposure Delayed Effects , Anti-Bacterial Agents/administration & dosage , Female , Humans , Incidence , Male , Manitoba/epidemiology , Pregnancy , Proportional Hazards Models , Risk FactorsABSTRACT
BACKGROUND: Recent studies have reported reduced risk of chronic lymphocytic leukemia (CLL) among statin users. However, the possibility that the effect of statins may differ by their chemical or pharmacodynamic properties has not been investigated. METHODS: In this nested case-control study, all Manitobans ages ≥40 years when diagnosed with CLL (as a first cancer) from 1999 to 2014 (n = 1,385) were matched (on gender, age, residence, and duration of insurance coverage) to cancer-free controls (n = 6,841). Using conditional logistic regression, statin use was analyzed by individual statins and groups: hydrophilic, low-potency lipophilic (fluvastatin and lovastatin), and high-potency lipophilic statins. RESULTS: Statin users constituted 27% and 28% of the CLL cases and controls, respectively. After adjusting for potential confounding by indication, patterns of healthcare utilization, and use of other drugs, CLL incidence was not associated with use of hydrophilic [odds ratio (OR) = 1.08; 95% confidence interval (CI), 0.86-1.34] or high-potency lipophilic (OR = 0.94; 95% CI, 0.79-1.11) statins. Low-potency lipophilic statins were associated with a lower risk of CLL (OR = 0.64; 95% CI, 0.45-0.92), with stronger association (OR = 0.44; 95% CI, 0.22-0.88) observed with more regular use (half to full standard dose on average). CONCLUSIONS: We found an association between low-potency lipophilic statin use and reduced CLL risk, with a possible dose-response effect. IMPACT: Although requiring replication in future studies, our findings suggest that the effect of statins on CLL risk may depend on their specific chemical or pharmacodynamic properties.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Leukemia, Lymphocytic, Chronic, B-Cell/chemically induced , Adult , Canada , Case-Control Studies , Female , Humans , Incidence , MaleABSTRACT
We quantified the contributions of leading causes of death and drug overdose to changes in life expectancy at birth over time and inequalities by sex and socioeconomic status in British Columbia. From 2014 to 2016, life expectancy at birth declined by 0.38 years and drug overdose deaths (mainly opioid-involved) contributed a loss of 0.12 years of the decrease. The analysis also demonstrated that the higher drug overdose mortality among males and among those in lower socioeconomic status communities contributed to a differential decrease in life expectancy at birth for males and for those in the latter category.
RÉSUMÉ: Nous avons quantifié la contribution des principales causes de décès et de surdose à l'évolution de l'espérance de vie à la naissance et aux disparités en matière de sexe et de situation socioéconomique en Colombie-Britannique. Entre 2014 et 2016, l'espérance de vie à la naissance a diminué de 0,38 an et les décès par surdose (principalement liés aux opioïdes) ont contribué à ce recul pour 0,12 an. L'analyse a également montré que le taux plus élevé de mortalité par surdose constaté chez les hommes et les membres des catégories socioéconomiques plus défavorisées a contribué à une diminution différentielle dans ces deux groupes de l'espérance de vie à la naissance.
Subject(s)
Drug Overdose/mortality , Life Expectancy/trends , British Columbia/epidemiology , Cause of Death , Female , Humans , Infant, Newborn , Male , Sex Factors , Socioeconomic FactorsABSTRACT
Background: Several epidemiological studies have shown a positive association between diabetes and increased risk of non-Hodgkin lymphoma (NHL), but the effect of diabetic treatment drugs such as metformin on the risk is unknown.Methods: We conducted a population-based nested case-control study involving 878 NHL cases and 4,364 controls diagnosed with diabetes. Use of metformin and other medications before diagnosis and medical condition histories were assessed using administrative databases. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for use of metformin, adjusting for confounders.Results: Risk of total NHLs is not associated with ever use of metformin (OR, 0.93; 95% CI, 0.79-1.10) among diabetic patients. NHL subtypes were also not associated with metformin use.Conclusions: Metformin use is not associated with overall or subtype NHL risk among diabetic patients.Impact: NHLs are etiologically heterogeneous and larger scale studies are warranted to test the potential effect of metformin by NHL subtype. Cancer Epidemiol Biomarkers Prev; 27(5); 610-2. ©2018 AACR.
Subject(s)
Diabetes Mellitus/drug therapy , Hypoglycemic Agents/adverse effects , Lymphoma, Non-Hodgkin/epidemiology , Metformin/adverse effects , Adult , Aged , Case-Control Studies , Female , Humans , Incidence , Male , Manitoba/epidemiology , Middle Aged , Odds RatioABSTRACT
Non-Hodgkin lymphomas (NHL) are a group of cancers with highly heterogeneous biology and clinical features. Statins are increasingly prescribed to prevent cardiovascular diseases. Early evidence shows a preventive effect of statins for some cancers, but their effect on NHL risk is unclear. We conducted a population-based nested case-control study involving 5,541 NHL cases and 27,315 controls matched for gender, age, place of residence and length of period of available prescription drug data. We assessed the use of statins prior to diagnosis (excluding the 12 months prior to the index date). We used conditional logistic regression models to estimate odds ratio (OR) and 95% confidence interval (CI) for use of any statin, adjusting for medical conditions, number of family physician visits for 5 years prior to index date, healthcare utilization, income and use of other medications. Over one-quarter of cases and controls were prescribed statins. Ever-use of any statin was associated with lower risk of Total NHL (OR = 0.82, 95% CI 0.76-0.89) and of certain subtypes including diffuse large B-cell lymphomas (DLBCL, OR = 0.77, 95% CI 0.65-0.92), plasma cell neoplasms (PCN, OR = 0.76, 95% CI 0.63-0.91) and other B-cell NHL (0.75, 0.59-0.95). Analysis by statin type suggested that the association was limited to high potency statin and lipophilic statin users. No clear duration or dose-response relationships were observed. Our findings provide evidence that statin use can reduce the risk of DLBCL and plasma cell lymphomas, but not other NHL types. Further studies are warranted to verify these associations and to examine the biological mechanisms.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Lymphoma, Non-Hodgkin/epidemiology , Adult , Aged , Case-Control Studies , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Logistic Models , Lymphoma, Non-Hodgkin/chemically induced , Male , Middle Aged , Risk FactorsABSTRACT
Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case-control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population-based prescription drug database. We used conditional logistic regression to model use of statins as a class and stratified analyses for groups defined by lipophilicity. Clinically significant PC was defined as Gleason score 8-10 OR stage C or D or III or IV at diagnosis. 12,745 cases of PC were risk-set matched on age and geographic location to 50,979 controls. Greater than 90% of subjects had prediagnosis drug exposure histories >15 years. 2,064 (16.2%) cases and 7,956 (15.6%) controls were dispensed one or more statin prescriptions. In multivariable models, ever prescription of statins was not associated with PC diagnosis (OR 0.97; 95% CI 0.90-1.05). Neither lipophilic statins (OR 0.96, 95% CI 0.88-1.04) nor hydrophilic statins (OR 1.06, 95% CI 0.95-1.20) impacted PC diagnosis. There was no effect of the dose or duration of statin use. Diagnosis of clinically significant PC decreased with statin use (OR 0.84, 95% CI 0.73-0.97). Statin use is not associated with overall PC risk, regardless of duration or dose of statin exposure. Statin use is associated with a decreased risk of clinically significant PC.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Canada/epidemiology , Case-Control Studies , Humans , Incidence , Logistic Models , Male , Middle Aged , Neoplasm GradingABSTRACT
Background: Non-hodgkin lymphoma (NHL) is one of the most common and deadly cancers. There is limited analysis of gene-environment interactions for the risk of NHL. This study intends to explore the interactions between genetic variants and environmental factors, and how they contribute to NHL risk. Methods: A case-control study was performed in Shanghai, China. The cases were diagnosed between 2003 and 2008 with patients aged 18 years or older. Samples and SNPs which did not satisfy quality control were excluded from the analysis. Weighted and unweighted genetic risk scores (GRS) and environmental risk scores were generated using clustering analysis algorithm. Univariate and multivariable logistic regression analyses were conducted. Moreover, genetics and environment interactions (G × E) were tested on the NHL cases and controls. Results: After quality control, there are 22 SNPs, 11 environmental variables and 5 demographical variables to be explored. For logistic regression analyses, 5 SNPs (rs1800893, rs4251961, rs1800630, rs13306698, rs1799931) and environmental tobacco smoking showed statistically significant associations with the risk of NHL. Odds ratio (OR) and 95% confidence interval (CI) was 10.82 (4.34-28.88) for rs13306698, 2.84 (1.66-4.95) for rs1800893, and 2.54 (1.43-4.58) for rs4251961. For G × E analysis, the interaction between smoking and dichotomized weighted GRS showed statistically significant association with NHL (OR = 0.23, 95% CI = [0.09, 0.61]). Conclusions: Several genetic and environmental risk factors and their interactions associated with the risk of NHL have been identified. Replication in other cohorts is needed to validate the results.
ABSTRACT
OBJECTIVE: To examine 30-year time trends in incidence, survival and mortality of lymphomas by subtype in Manitoba, Canada. METHODS: Lymphoma cases diagnosed between 1984 and 2013 were classified according to the 2008 WHO classification system for lymphoid neoplasms. Death data (1984-2014) were obtained from the Manitoba Vital Statistics Agency. To examine time trends in incidence and mortality, we used joinpoint regression to estimate annual percentage change and average annual percentage change. Age-period-cohort modelling was conducted to measure the effects of age, period and cohort on incidence and mortality time trends. We estimated age-specific and standardised 5-year relative survival and used Poisson regression model to test time trends in relative survival. RESULTS: Total Hodgkin lymphoma (HL) incidence in men and women was stable during the study period. Age-standardised total non-Hodgkin lymphoma (NHL) incidence increased by 4% annually until around 2000, and the trend varied by sex and NHL subtype. Total HL mortality continuously declined (by 2.5% annually in men and by 2.7% annually in women), while total NHL mortality increased (by 4.4% annually in men until 1998 and by 3.2% annually in women until 2001) and then declined (by 3.6% annually in men and by 2.5% annually in women). Age-standardised 5-year relative survival for HL improved from 72.6% in 1984-1993 to 85.8% in 2004-2013, and for NHL from 57.0% in 1984-1993 to 67.5% in 2004-2013. Survival improvement was also noted for NHL subtypes, although the extent varied, with the greatest improvement for follicular lymphoma (from 65.3% in 1984-1993 to 87.6% in 2004-2013). CONCLUSIONS: Time trends were generally consistent with those reported in other jurisdictions in total HL and NHL incidence, but were unique in incidence for HL and for NHL subtypes chronic/small lymphocytic leukaemia/lymphoma, diffuse large B cell lymphoma and follicular lymphoma. Survival improvements and mortality reductions were seen for HL and NHL in both sexes.
Subject(s)
Lymphoma/classification , Lymphoma/mortality , Adult , Age Distribution , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Incidence , Male , Manitoba/epidemiology , Middle Aged , Population Surveillance , Registries , Sex Distribution , Survival Analysis , Young AdultABSTRACT
OBJECTIVES: To test for time and spatial trends in lymphoid malignancies, including lymphoid leukemia (LL), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL), in children and adolescents in the province of Manitoba, Canada. METHODS: Incident cases diagnosed between 1984 and 2013 were identified from the Manitoba Cancer Registry. We assessed time trends in age-standardized incidence rates using joinpoint regression and in 5-year relative survival using Poisson regression model. Kulldorff's scan method was used to assess spatial variation and clustering. RESULTS: Age-standardized incidence rates (per million person-years) in males and females were 34.0 (95% confidence interval [CI] 28.9-39.1) and 26.2 (95% CI 21.5-30.7) for LL, 10.5 (95% CI 7.7-13.3) and 12.5 (95% CI 9.4-15.7) for HL, 12.5 (95% CI 9.3-15.4) and 7.7 (95% CI 5.2-10.2) for NHL (except for Burkitt lymphomas), and 3.2 (95% CI 1.6-4.7) and 1.5 (95% CI 0.4-2.5) for Burkitt lymphomas. Age- and sex- standardized LL incidence rate increased 1.4% (95% CI 0.3%-2.5%) per year, while the changes for HL and NHL incidence rates were not statistically significant. There were geographic differences in age-standardized incidence rates for LL, HL, and NHL and spatial clusters were detected in southern part of the province. Five-year relative survival has improved over time and there was no difference between rural and urban areas. CONCLUSIONS: Lymphoid leukemia incidence rate increased over time and varied by geographic area. Further research should examine the factors contributing to these trends.
Subject(s)
Leukemia, Lymphoid/epidemiology , Lymphoma/epidemiology , Adolescent , Child , Child, Preschool , Female , Humans , Incidence , Male , Manitoba/epidemiology , Survival AnalysisABSTRACT
We undertook a hospital-based case-control study to examine the associations between single nucleotide polymorphisms (SNPs) in selected immunoregulatory genes and non-Hodgkin lymphoma (NHL) risk in a Chinese population. One hundred and sixty-nine NHL patients diagnosed according to the World Health Organization (WHO) 2001 standard and 421 controls were recruited. Nine SNPs in three genes (IL-10, IL-1RN, and TNF-α) were selected based on predicted functions and previous study findings. Genetic association analysis was performed using the Cochran-Armitage trend test and multiple logistic regression. Four SNPs were associated with an increased risk of overall NHL: odds ratio per minor allele [ORper-minor-allele] and 95% confidence interval [CI] were 2.64 (1.75-3.98) for IL-10 rs1800893, 2.67 (1.72-4.16) for IL-1RN rs4251961, 1.80 (1.24-2.63) for TNF- α rs1800630, and 1.55 (1.02-2.37) for TNF- α rs2229094. These SNPs were also associated with an increased risk of diffuse large B-cell lymphoma (DLBCL). In addition, another SNP (TNF- α rs1041981) was associated with an increased risk of DLBCL (ORper-minor-allele=1.73, 95% CI 1.14-2.61). The findings provide evidence on the role of these immunoregulatory gene variants in NHL etiology.
Subject(s)
Biomarkers, Tumor/genetics , Interleukin 1 Receptor Antagonist Protein/genetics , Interleukin-10/genetics , Lymphoma, Non-Hodgkin/genetics , Polymorphism, Single Nucleotide , Tumor Necrosis Factor-alpha/genetics , Aged , Asian People/genetics , Case-Control Studies , Chi-Square Distribution , China , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Logistic Models , Lymphoma, Large B-Cell, Diffuse/ethnology , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Non-Hodgkin/ethnology , Lymphoma, Non-Hodgkin/immunology , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Phenotype , Risk FactorsABSTRACT
Evidence on the effect of statin use on non-Hodgkin lymphoma (NHL) is not clear. We conducted a systematic review and meta-analysis to examine the associations between statin use and NHL risk and survival. We searched multiple literature sources up to October 2014 and identified 10 studies on the risk of diagnosis with NHL and 9 studies on survival. Random effects model was used to calculate pooled odds ratio (PORs) for risk and pooled hazard ratio (PHR) for survival. Heterogeneity among studies was examined using the Tau-squared and the I-squared (I2 ) tests. Statin use was associated with reduced risk for total NHL (POR = 0.82, 95% CI 0.69-0.99). Among statin users, there was a lower incidence risk for marginal zone lymphoma (POR = 0.54, 95% CI 0.31-0.94), but this was not observed for other types of NHL. However, statin use did not affect overall survival (PHR = 1.02, 95% CI 0.99-1.06) or event-free survival (PHR = 0.99, 95% CI 0.87-1.12) in diffuse large B-cell lymphoma. There is suggestive epidemiological evidence that statins decrease the risk of NHL, but they do not influence survival in NHL patients. Copyright © 2015 John Wiley & Sons, Ltd.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lymphoma, Non-Hodgkin/prevention & control , Humans , Lymphoma, B-Cell, Marginal Zone/prevention & control , Lymphoma, Non-Hodgkin/mortality , RiskABSTRACT
Bendamustine (BEN) has structural similarities to an alkylating agent and a nucleoside analog, and effective against tumor cells that are resistant to standard therapy. In this study we compared the activities of BEN against that of the alkylating agent, chlorambucil (CLB), and the nucleoside analogs, fludarabine (FLU) and deoxyadenosine/pentostatin (dADO/PEN), in primary chronic lymphocytic leukemia (CLL) cells in vitro. Cross-resistance was observed between BEN, CLB and FLU, with previously treated patients or those with a deletion 17p being most resistant. In contrast, some resistant CLL cells retained moderate sensitivity to dADO/PEN. Like FLU and CLB, BEN induced apoptosis through both the mitochondrial and death receptor pathways. There was a greater increase in DNA double-strand breaks (DSB) following FLU, as compared to BEN and CLB. Synergistic cytotoxicity was seen on combining BEN or CLB with FLU or dADO/PEN, but not when combining BEN with CLB. These results demonstrate that BEN acts as an alkylating agent, demonstrates cross-resistance to CLB and FLU and resistance to cells with a del 17p. Synergistic cytotoxic activity was seen between BEN and dADO/PEN suggesting that the combination of BEN and PEN should be evaluated in the clinic.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bendamustine Hydrochloride/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Adenosine Deaminase Inhibitors , Apoptosis/drug effects , Chlorambucil/therapeutic use , DNA Breaks, Double-Stranded/drug effects , Deoxyadenosines/therapeutic use , Drug Synergism , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Pentostatin/therapeutic use , Tumor Cells, CulturedABSTRACT
BACKGROUND: Hospital readmission is costly and potentially avoidable. The concept of virtual wards as a new model of care is intended to reduce hospital readmissions by providing short-term transitional care to high-risk and complex patients in the community. In order to provide information regarding the development of virtual wards in the Winnipeg Health Region, Canada, this study used spatial statistics to identify geographic variations of hospital readmissions in 25 neighborhood clusters. METHODS: The data were obtained from the Population Health Research Data Repository housed at the Manitoba Centre for Health Policy. We used a Bayesian Disease Mapping approach which applied Markov chain Monte Carlo (MCMC) for cluster detection. RESULTS: Between 2005/06 and 2008/09, 123,842 patients were hospitalized in all Winnipeg hospitals. Of these, 41,551 (33%) were readmitted to hospital in the year following discharge. Most of these readmitted patients (89.4%) had 1-2 readmissions, while 11.6% of readmitted patients had more than 2 readmissions after initial discharge. The smoothed age- and sex- adjusted relative risk rates of hospital readmission in 25 Winnipeg neighborhood clusters ranged between 0.73 and 1.27. We found that there were spatial cluster variations of hospital readmission across the Winnipeg Health Region. Seven neighborhood clusters are more likely to be significant potential clusters for hospital readmissions (p < .05), while six neighborhood clusters are less likely to be significant potential clusters. CONCLUSIONS: This study provides the foundation and implementation guide for the Winnipeg Regional Health Authority virtual ward program. The findings will also help to improve long-term condition management in community settings and will help program planners to assure the efficient use of healthcare resources.
Subject(s)
Continuity of Patient Care/statistics & numerical data , Patient Discharge/statistics & numerical data , Patient Readmission/statistics & numerical data , Telemedicine/statistics & numerical data , Adult , Age Factors , Aged , Aged, 80 and over , Bayes Theorem , Female , Humans , Male , Manitoba , Middle Aged , Residence Characteristics , Sex FactorsABSTRACT
OBJECTIVE: A number of predictive models have been developed to identify patients at risk of hospital readmission. Most of these have focused on readmission within 30 days of discharge. We used population-based health administrative data to develop a predictive model for hospital readmission within 12 months of discharge in Winnipeg, Canada. METHODS: This was a retrospective cohort study with derivation and validation data sets. Multivariable logistic regression analyses were performed and factors significantly associated with readmission were selected to construct a risk scoring tool. RESULTS: Several variables were identified that predicted readmission (i.e. older age, male, at least one hospital admission in the previous two years, an emergent (index) hospital admission, Charlson comorbidity score >0 and length of stay). Discrimination power was acceptable (C statistic =0.701). At a median risk score threshold, the sensitivity, specificity, positive and negative predictive values were 45.5%, 79%, 68.8% and 58.6%. CONCLUSIONS: This predictive model demonstrated that hospital readmission within 12 months of discharge can be reasonably well predicted based on administrative data. It will help health care providers target interventions to prevent unnecessary hospital readmissions.
Subject(s)
Patient Readmission/statistics & numerical data , Risk Assessment/methods , Adult , Age Distribution , Aged , Aged, 80 and over , Comorbidity , Databases, Factual , Female , Humans , Length of Stay , Logistic Models , Male , Manitoba , Middle Aged , Retrospective Studies , Risk Assessment/standards , Risk Factors , Sex DistributionABSTRACT
Epidemiological study findings regarding the association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of non-Hodgkin lymphoma (NHL) have been inconsistent. We aimed to systematically review epidemiological studies of the association and calculate pooled relative risks using meta-analytic methods. We searched eight electronic literature databases and three clinical trial registers to identify all studies (including observational studies and randomized clinical trials) of the association published prior to October 2013. Identified studies were independently reviewed by two researchers. We used a random effects model to calculate pooled odds ratio (PORs). Heterogeneity amongst studies was examined using Cochran's Q and I-squared (I(2)) tests; and sources of heterogeneity were explored using subgroup and meta-regression analyses. A total of 17 studies (12 case-control studies and five cohort studies), all adult studies, were included. Use of NSAIDs was not associated with overall risk of NHL [POR = 1.05, and 95% confidence interval (95% CI) 0.90-1.22] or NHL subtypes including B-cell lymphoma, T-cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Aspirin use was associated with reduced risk of CLL/SLL (POR = 0.70, 95% CI 0.54-0.91) but not with the risk of all NHLs (POR = 1.02, 95% CI 0.89-1.17). Use of non-aspirin NSAIDs was associated with increased risk of NHL (POR = 1.41, 95% CI 1.01-1.97) amongst females only. The epidemiologic evidence remains inconclusive. Effects of NSAIDs may differ by drug type, NHL subtype, and sex and more studies taking into consideration these differences are needed.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Humans , Risk FactorsABSTRACT
BACKGROUND: The majority of internet-based anxiety and depression intervention studies have targeted adults. An increasing number of studies of children, youth, and young adults have been conducted, but the evidence on effectiveness has not been synthesized. The objective of this research is to systematically review the most recent findings in this area and calculate overall (pooled) effect estimates of internet-based anxiety and/or depression interventions. METHODS: We searched five literature databases (PubMed, EMBASE, CINAHL, PsychInfo, and Google Scholar) for studies published between January 1990 and December 2012. We included studies evaluating the effectiveness of internet-based interventions for children, youth, and young adults (age <25 years) with anxiety and/or depression and their parents. Two reviewers independently assessed the risk of bias regarding selection bias, allocation bias, confounding bias, blinding, data collection, and withdrawals/dropouts. We included studies rated as high or moderate quality according to the risk of bias assessment. We conducted meta-analyses using the random effects model. We calculated standardized mean difference and its 95% confidence interval (95% CI) for anxiety and depression symptom severity scores by comparing internet-based intervention vs. waitlist control and internet-based intervention vs. face-to-face intervention. We also calculated pooled remission rate ratio and 95% CI. RESULTS: We included seven studies involving 569 participants aged between 7 and 25 years. Meta-analysis suggested that, compared to waitlist control, internet-based interventions were able to reduce anxiety symptom severity (standardized mean difference and 95% CI = -0.52 [-0.90, -0.14]) and increase remission rate (pooled remission rate ratio and 95% CI =3.63 [1.59, 8.27]). The effect in reducing depression symptom severity was not statistically significant (standardized mean difference and 95% CI = -0.16 [-0.44, 0.12]). We found no statistical difference in anxiety or depression symptoms between internet-based intervention and face-to-face intervention (or usual care). CONCLUSIONS: The present analysis indicated that internet-based interventions were effective in reducing anxiety symptoms and increasing remission rate, but not effective in reducing depression symptom severity. Due to the small number of higher quality studies, more attention to this area of research is encouraged. TRIAL REGISTRATION: PROSPERO registration: CRD42012002100.
Subject(s)
Anxiety Disorders/therapy , Depressive Disorder/therapy , Internet , Psychotherapy/methods , Adolescent , Child , Health Services Accessibility , Humans , Randomized Controlled Trials as Topic , Young AdultABSTRACT
OBJECTIVE: To review the quality of Internet-based mental health intervention studies and their methodological challenges. MATERIALS AND METHODS: We searched multiple literature databases to identify relevant studies according to the Population, Interventions, Comparators, Outcomes, and Study Design framework. Two reviewers independently assessed selection bias, allocation bias, confounding bias, blinding, data collection methods, and withdrawals/dropouts, using the Quality Assessment Tool for Quantitative Studies. We rated each component as strong, moderate, or weak and assigned a global rating (strong, moderate, or weak) to each study. We discussed methodological issues related to the study quality. RESULTS: Of 122 studies included, 31 (25%), 44 (36%), and 47 (39%) were rated strong, moderate, and weak, respectively. Only five studies were rated strong for all of the six quality components (three of them were published by the same group). Lack of blinding, selection bias, and low adherence were the top three challenges in Internet-based mental health intervention studies. CONCLUSIONS: The overall quality of Internet-based mental health intervention needs to improve. In particular, studies need to improve sample selection, intervention allocation, and blinding.