Medication adherence in patients with asthma using once-daily versus twice-daily ICS/LABAs.

OBJECTIVE: This real-world observational study compared medication adherence and persistence among patients with asthma receiving the once-daily inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) fluticasone furoate/vilanterol (FF/VI) versus the twice-daily ICS/LABAs budesonide/formoterol (B/F) and fluticasone propionate/salmeterol (FP/SAL). METHODS: This retrospective cohort study conducted using IQVIATM Health Plan Claims Data included patients with asthma ≥18 years of age initiating ICS/LABA therapy with FF/VI, B/F, or FP/SAL between January 1, 2014 and June 30, 2016 (index date). Patients had ≥12 months and ≥3 months of continuous eligibility pre- and post-index date, respectively. Patients receiving FF/VI were separately matched 1:1 with patients receiving B/F or FP/SAL using propensity score matching (PSM) and multivariable regression to balance baseline covariates between cohorts. The primary endpoint was medication adherence, measured by proportion of days covered (PDC). Secondary endpoints included proportion of patients achieving PDC ≥ 0.5 and PDC ≥ 0.8 and persistence with index medication, measured by time to discontinuation (>45-day gap in therapy). RESULTS: After PSM, 3,764 and 3,339 patients receiving FF/VI were matched with patients receiving B/F or FP/SAL, respectively. Mean PDC was significantly higher for FF/VI versus B/F (0.453 vs 0.345; adjusted p < 0.001) and FP/SAL (0.446 vs 0.341; adjusted p < 0.001). The proportion of patients achieving PDC ≥ 0.5 or PDC ≥ 0.8, and treatment persistence were significantly higher for FF/VI versus B/F and FP/SAL (all p < 0.001). CONCLUSIONS: In this real-world study, patients initiating FF/VI had better adherence and lower risk of discontinuing treatment versus B/F or FP/SAL, suggesting that once-daily ICS/LABA treatment might improve adherence and persistence compared with twice-daily alternatives.

EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: The objective of this study was to investigate real-world EGFR mutation testing in patients with metastatic non-small cell lung cancer (NSCLC) upon progression on first-/second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI), and subsequent treatments received. METHODS: Flatiron Health electronic health records-derived database was used to identify adult patients with metastatic NSCLC treated with first-/second-generation EGFR-TKI from 11/2015-09/2017, with start of first EGFR-TKI defined as the index date. Patients were stratified by receipt of EGFR-TKI as first-line (1 L) or later-line (2 L+) treatment. Mutation testing and subsequent therapies following first-/second-generation EGFR-TKI were described. RESULTS: Overall, 782 patients (1 L = 435; 2 L+ =347) were included. Median age was 69.0 years, 63.6% were female, 56.3% were white, 87.1% were treated in community-based practices, and 30.1% of patients died during the study period; median follow-up was 309.0 days. Among the 294 (1 L = 160; 2L+ =134) patients who received subsequent therapies, treatments included chemotherapy only (1 L = 15.6%; 2L+ =21.6%), immunotherapy only (1 L = 13.8%; 2 L+ =41.0%), and targeted therapies (1 L = 70.0%; 2 L+ =36.6%). Specifically, 40 (25.0%) 1 L patients and 7 (5.2%) 2 L+ patients received osimertinib as subsequent therapy. Before the start of subsequent therapy, EGFR T790M resistance mutation testing was performed in 88 (29.9%) patients (1 L = 63 [39.4%]; 2 L+ =25 [18.7%]). Of these patients, 25 (28.4%) were T790M positive, among whom 24 (96.0%) received osimertinib. CONCLUSIONS: A third of patients received subsequent therapies on disease progression; only 30% of these were tested for EGFR-TKI resistance mutation, prior to receiving subsequent therapies. These results highlight the importance of choosing treatments in the 1 L setting that optimize benefits for patients with EGFR-mutated NSCLC.

Identification of incident pancreatic cancer in Ontario administrative health data: A validation study.

PURPOSE: To validate three approaches for identifying incident cases of pancreatic cancer in Ontario administrative claims data. METHODS: We created a cohort using Ontario (Canada) administrative health data from 2002 to 2012 and identified cases of pancreatic cancer with three approaches, using the Ontario Cancer Registry (OCR) as the reference standard. In the any diagnosis approach, cases were defined by primary or secondary diagnostic codes for pancreatic cancer in outpatient or inpatient records. In the any inpatient diagnosis approach, cases were defined using only diagnoses in hospital discharge abstracts. In the algorithm approach, cases were identified by an algorithm that combined the first two approaches. Comparing each approach to the OCR, we calculated the expected value and 95% confidence interval (CI) of the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We also compared the event dates using each approach with those recorded in the OCR. RESULTS: Among a total of 12 060 837 patients in Ontario administrative health data sources, 13 999 incident pancreatic cancer cases were identified in the OCR. Sensitivity ranged from 72.5% (algorithm) to 97.5% (any diagnosis), and PPV ranged from 38.4% (any diagnosis) to 78.9% (any inpatient diagnosis). Specificity and NPV were ~100% for all approaches. The median absolute difference in cancer event date ranged 0 to 15 days. The any inpatient diagnosis method had the highest PPV (78.9%; 95% CI: 78.2-79.5%) and moderate sensitivity (86.6%; 95% CI: 86.0-87.2%). CONCLUSION: Inpatient diagnoses of pancreatic cancer in Ontario administrative heath data are suitable for pancreatic cancer case identification.

The effect of statins on influenza-like illness morbidity and mortality.

PURPOSE: The effect of statins on cytokine-mediated inflammatory responses may impact on the prognosis of influenza. We assessed whether statin use decreases the incidence of adverse influenza-related outcomes. Additionally, we used a new-user study design to minimize healthy user bias. We further examined the possibility of non-causal associations by using unrelated outcomes. METHODS: We used the UK Clinical Practice Research Datalink to identify all patients aged 30 or older diagnosed with influenza-like illness during 1997-2010. Statin users were compared with propensity score-matched patients not receiving statins. The outcome was hospitalization for influenza or pneumonia or death in the 30 days following influenza diagnosis. Logistic regression estimated cumulative incidence ratios. RESULTS: The study cohort included 5181 statin users matched to 5181 non-users. The 30-day incidence of hospitalization or death was 3.5% in statin users and 5.2% in non-users, resulting in a 27% lower incidence with statin use (cumulative incidence ratio: 0.73, 95%CI: 0.59-0.89). New statin users were less protected against our composite outcome. The effect of statins was less pronounced among those with respiratory and cardiac disease. Statin use was shown to be associated with a non-statistically significant risk reduction of motor vehicle accident and burns. CONCLUSION: The attenuation of the effect of statins with the new-user design, supporting evidence from the assessment of effect modification, and additional sub-analyses evaluating the effect of statins on non-related outcomes suggest that the beneficial effect of statins on influenza-related adverse outcomes may be explained by a healthy user bias. Copyright © 2016 John Wiley & Sons, Ltd.

Index-based dietary patterns and risk of esophageal and gastric cancer in a large cohort study.

BACKGROUND & AIMS: Diet could affect risk for esophageal and gastric cancers, but associations have been inconsistent. The diet is complex, so studies of dietary patterns, rather than studies of individual foods, might be more likely to identify cancer risk factors. There is limited research on index-based dietary patterns and esophageal and gastric cancers. We prospectively evaluated associations between the Healthy Eating Index-2005 (HEI-2005) and alternate Mediterranean Diet (aMED) scores and risk of esophageal and gastric cancers. METHODS: We analyzed data from 494,968 participants in the National Institutes of Health-AARP Diet and Health study, in which AARP members (age, 51-70 y) completed a self-administered baseline food frequency questionnaire between 1995 and 1996. Their answers were used to estimate scores for each index. RESULTS: During the follow-up period (1995-2006), participants developed 215 esophageal squamous cell carcinomas (ESCCs), 633 esophageal adenocarcinomas (EACs), 453 gastric cardia adenocarcinomas, and 501 gastric noncardia adenocarcinomas. Higher scores from the HEI-2005 were associated with a reduced risk of ESCC (comparing the highest quintile with the lowest quintile: hazard ratio, 0.51; 95% confidence interval, 0.31-0.86; Ptrend = .001) and EAC (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; Ptrend = .01). We observed an inverse association between ESCC, but not EAC, and a higher aMED score (meaning a higher-quality diet). HEI-2005 and aMED scores were not associated significantly with gastric cardia or noncardia adenocarcinomas. CONCLUSIONS: By using data collected from 1995 through 2006 from the National Institutes of Health-AARP Diet and Health Study, HEI-2005 and aMED scores were associated inversely with risk for esophageal cancers, particularly ESCC. Adherence to dietary recommendations might help prevent esophageal cancers.

Canadian healthcare capacity gaps for disease-modifying treatment in Huntington's disease: a survey of current practice and modelling of future needs.

OBJECTIVES: Disease-modifying therapies in development for Huntington's disease (HD) may require specialised administration and additional resource capacity. We sought to understand current and future capacity for HD management in Canada considering the possible introduction of an intrathecal (IT) disease-modifying treatment (DMT). DESIGN, SETTING AND PARTICIPANTS: Using a case study, mixed methods framework, online surveys followed by semistructured interviews were conducted in late 2020 and early 2021. Neurologists from Canadian HD (n=16) and community (n=11) centres and social workers (n=16) were invited to complete online surveys assessing current HD management and potential capacity to support administration of an IT DMT. OUTCOME MEASURES: Survey responses, anticipated demand and assumed resource requirements were modelled to reveal capacity to treat (ie, % of eligible patients) by centre. Resource bottlenecks and incremental support required (full-time equivalent, FTE) were also determined. RESULTS: Neurologists from 15/16 HD centres and 5/11 community centres, plus 16/16 social workers participated. HD centres manage 94% of patients with HD currently seeking care in Canada, however, only 20% of IT DMT-eligible patients are currently seen by neurologists. One-third of centres have no access to nursing support. The average national incremental nursing, room, neurologist and social worker support required to provide IT DMT to all eligible patients is 0.73, 0.36, 0.30 and 0.21 FTE per HD centre, respectively. At peak demand, current capacity would support the treatment of 6% of IT DMT-eligible patients. If frequency of administration is halved, capacity for IT-DMT administration only increases to 11%. CONCLUSIONS: In Canada, there is little to no capacity to support the administration of an IT DMT for HD. Current inequitable and inadequate resourcing will require solutions that consider regional gaps and patient needs.

Systematic Review of Motor Function Scales and Patient-Reported Outcomes in Spinal Muscular Atrophy.

ABSTRACT: Spinal muscular atrophy is a heterogeneous disease that results in loss of motor function. In an evolving treatment landscape, establishing the suitability and limitations of existing motor function scales and patient-reported outcomes used to monitor patients with this disease is important. A systematic review was conducted to examine utility of motor function scales and patient-reported outcomes in evaluating patients with spinal muscular atrophy. Published literature was reviewed up to June 2021 with no start date restriction. Of the reports screened, 122 were deemed appropriate for inclusion and are discussed in this review (including 24 validation studies for motor function scales or patient-reported outcomes). Fifteen motor function scales and patient-reported outcomes were identified to be commonly used (≥5 studies), of which 11 had available validation assessments. Each instrument has its strengths and limitations. It is imperative that the patient population (e.g., age, mobility), goals of treatment, and outcomes or endpoints of interest be considered when selecting the appropriate motor function scales and patient-reported outcomes for clinical studies.

Epidemiology and economic burden of Huntington's disease: a Canadian provincial public health system perspective.

AIMS: To evaluate the epidemiology, healthcare resource utilization, and direct healthcare costs associated with Huntington's disease in a Canadian setting with a universal healthcare system. MATERIALS AND METHODS: Using Albertan administrative health data, a retrospective cohort was identified applying an algorithm requiring two HD diagnostic codes within two years, using the first record as the index date (i.e. proxy for diagnosis date), from 1 April 2010 to 31 March 2019 for patients ≥21 years old. Incidence/prevalence measures were evaluated from 1 April 2010 to 31 March 2019, while healthcare resource utilization and healthcare costs per person-year (inflated to 2020 Canadian dollars) were evaluated from index to the end of follow-up (death, moved out of province, or 31 March 2020). RESULTS: Mean [standard deviation] age at index (n = 395) was 53.9 [13.8] years and 53.7% were female. From 2010 to 2019, annual HD incidence varied between 0.47 and 1.21/100,000 person-years and HD prevalence increased from 7.25 to 9.33/100,000 persons. The mean number of visits per person-year for general and specialist practitioners was 19.2 [18.8] and 12.2 [25.5], respectively. The mean total all-cause direct healthcare costs were $23,211 [$38,599] per person-year, with hospitalizations accounting for 57.8% of all-cause costs. Costs were higher among individuals with a long-term care stay, a proxy for disease severity. LIMITATIONS AND CONCLUSIONS: This study utilizes administrative health data to describe the epidemiology of HD and utilization of publicly funded care by individuals with HD. While administrative data presents limitations since it is not collected for research purposes, it provides a population-level examination of the burden of HD. There was a substantial economic burden associated with HD in a Canadian setting.

Disease Burden of Huntington's Disease (HD) on People Living with HD and Care Partners in Canada.

BACKGROUND: Huntington's disease (HD) has been shown to reduce health-related quality of life (HRQoL) and affect healthcare resource utilization (HRU) among patients and care partners internationally but has not been studied specifically in the Canadian context. OBJECTIVE: To characterize the burden of HD on individuals with HD and care partners of individuals with HD in Canada. METHODS: An online survey was distributed (September 14-November 23, 2020) through patient organizations to collect data on demographic and clinical characteristics, as well as: HRQoL, measured using the 36-Item Short-Form Health Survey (SF-36v1); HRU, measured using the Client Service Receipt Inventory (CSRI); and care partner burden, measured using the Caregiver Strain Index (CSI) and Huntington's Disease Quality of Life Battery for Carers (HDQoL-C). Descriptive statistics were used to report data and compare subgroups. RESULTS: A total of 62 adult individuals with HD (or their proxies) and 48 care partners met defined eligibility criteria. The mean [standard deviation] age was 51.2 [13.8] and 58.1 [13.9] years for individuals with HD and care partner respondents, respectively. For individuals with HD, the greatest HRQoL burden (i.e., lowest score) was for the SF-36v1 Role -Physical scale (46.8 [42.9]). HRU was higher for some services (e.g., general practitioner visits) for respondents who had experienced motor onset transition. Among care partners, 55.3% experienced high strain, as indicated by the CSI. The HDQoL-C showed the greatest HRQoL burden in feelings about life (45.1 [17.9]). CONCLUSION: This study quantified the substantial burden on individuals with HD and care partners in Canada, addressing a critical knowledge gap that can affect the availability of and access to healthcare services.

Epidemiology, healthcare resource utilization and healthcare costs for spinal muscular atrophy in Alberta, Canada.

AIMS: Spinal muscular atrophy (SMA) is a progressive neuromuscular disease associated with the degeneration of motor neurons in the brainstem and spinal cord. Studies examining the epidemiology and economic impact of SMA are limited in Canada. This study aimed to estimate the epidemiology as well as healthcare resource utilization (HRU) and healthcare costs for children with SMA in Alberta, Canada. MATERIALS AND METHODS: We conducted a retrospective study using anonymized data from administrative healthcare databases provided by Alberta Health. Data from 1 April 2010 to 31 March 2018, were extracted for patients <18 years of age identified with SMA. Five-year incidence and prevalence were calculated for cases identified between 1 April 2012 and 31 March 2017. HRU and healthcare costs were assessed one year after SMA diagnosis, including hospitalizations, physician visits, ambulatory care visits and long-term care admissions. RESULTS: The five-year incidence and prevalence of pediatric onset SMA were 1.03 per 100,000 person-years and 9.97 per 100,000 persons, respectively. General practitioner, specialist, and ambulatory care visits were common among children with SMA in the first-year post-diagnosis. The mean (SD) total annual direct cost per patient in the first-year post-diagnosis was $29,774 ($38,407); hospitalizations accounted for 41.7% of these costs ($12,412 [$21,170]), followed by practitioner visits at 32.3% ($9,615 [$13,054]), and ambulatory care visits at 26.0% ($7,746 [$9,988]). CONCLUSIONS: Children with SMA experience substantial HRU, particularly for hospitalizations and practitioner visits, following diagnosis. Given the high costs of SMA, timely access to effective treatment strategies, such as the novel survival motor neuron (SMN)-restoring treatments recently approved for use, are needed to improve health outcomes and HRU.

US Integrated Delivery Networks Perspective on Economic Burden of Patients with Treatment-Resistant Depression: A Retrospective Matched-Cohort Study.

OBJECTIVE: Our objective was to assess healthcare resource utilization (HRU) and costs among patients with major depressive disorder (MDD) with and without treatment-resistant depression (TRD) and those without MDD in US Integrated Delivery Networks (IDNs). METHODS: This was a retrospective matched-cohort study. The Optum© Integrated Claims Electronic Health Record de-identified database was used to identify adult patients with TRD (January 2011-June 2017) across US IDNs. TRD patients were propensity score matched 1:1 with non-TRD MDD and non-MDD patients on demographics. Rates of HRU and costs were compared up to 2 years following the first antidepressant pharmacy claim (or randomly imputed date for non-MDD patients) using negative binomial and ordinary least squares regressions, respectively, with 95% confidence intervals (CIs) from nonparametric bootstraps (costs only) adjusted for baseline comorbidity index and costs. RESULTS: All 1582 TRD patients were matched to non-TRD MDD and non-MDD patients and evaluated. TRD patients were on average 46 years old, and 67% were female. Mean duration of observation was 20.1, 19.6, and 17.9 months in the TRD, non-TRD MDD, and non-MDD cohorts, respectively. Patients with TRD had significantly higher rates of HRU than did non-TRD MDD patients (inpatient visits 0.35 vs. 0.16 per patient per year [PPPY]; adjusted incidence rate ratio [IRR] 2.04 [95% CI 1.74-2.39]) and non-MDD patients (0.35 vs. 0.09 PPPY, adjusted IRR 3.05 [95% CI 2.54-3.66]). TRD patients incurred significantly higher costs PPPY than did non-TRD MDD patients ($US25,807 vs. 13,701, adjusted cost difference $US9479 [95% CI 7071-11,621]) and non-MDD patients ($US25,807 vs. 8500, adjusted cost difference $US11,433 [95% CI 8668-13,876]). CONCLUSIONS: HRU and costs associated with TRD are significant in US IDNs.

Characterizing Real-World Use Of Tiotropium In Asthma In The USA.

BACKGROUND: Tiotropium bromide (TIO) is a long-acting muscarinic antagonist recommended as an add-on therapy option for patients with uncontrolled asthma on inhaled corticosteroids (ICS) and long-acting ß2-agonists (LABA). However, real-world data on TIO use in asthma remains limited. To identify unmet needs, this study explored the use of TIO in US patients with asthma. METHODS: This retrospective cohort study used IQVIATM Health Plan Claims Data (October 1, 2014─December 31, 2016). Patients with asthma diagnoses initiating TIO 1.25 or 2.5 mcg after September 16, 2015 (first dispensing on index date) with ≥6 and ≥3 months continuous enrollment pre- and post-index, respectively, were identified. Patients with COPD diagnoses were excluded. Baseline characteristics, healthcare resource utilization and costs, and treatment patterns before and following TIO initiation were described for TIO cohorts and subgroups classified by concomitant medications received during the 30-day period after initiation. RESULTS: The study included 766 TIO 1.25 mcg and 1055 TIO 2.5 mcg users. In the TIO 1.25 mcg cohort, 16% (126/766) used TIO monotherapy while 61% (465/766) used TIO+ICS/LABA± leukotriene receptor antagonists (triple therapy). In TIO 1.25 mcg monotherapy and triple therapy subgroups, 39% and 49% were treated by allergists/pulmonologists, 27% and 48% experienced a moderate/severe asthma exacerbation, and 50% and 68% used rescue oral corticosteroids during the baseline period, respectively. Following triple therapy initiation, 44% of patients discontinued ICS within 6 months. The TIO 2.5 mcg cohort demonstrated similar trends. CONCLUSION: This study provided insights into real-world US use of TIO in asthma. Overall, 16-19% of patients received TIO monotherapy and had high baseline exacerbation rates, suggesting that additional ICS-containing medication may be beneficial. Patients initiating triple therapy were among the most severe, with high baseline exacerbation rates and rescue medication use, and had high post-treatment ICS discontinuation rates, suggesting unmet needs in this population.

Medication adherence and persistence in chronic obstructive pulmonary disease patients receiving triple therapy in a USA commercially insured population.

INTRODUCTION: This longitudinal, retrospective cohort study of patients with COPD describes baseline characteristics, adherence, and persistence following initiation of inhaled corticosteroids (ICS)/long-acting ß2-agonists (LABA)/long-acting muscarinic antagonists (LAMA) from multiple inhaler triple therapy (MITT). METHODS: Patients aged ≥40 years receiving MITT between January 2012 and September 2015 were identified from the IQVIA™ Real-world Data Adjudicated Claims-USA database. MITT was defined as subjects with ≥1 overlapping days' supply of three COPD medications (ICS, LABA, and LAMA). Adherence (proportion of days covered, PDC) and discontinuation (defined as a gap of 1, 30, 60, or 90 days of supply in any of the three components of the triple therapy) were calculated for each patient over 12 months of follow-up. In addition, analyses were stratified by number of inhalers. RESULTS: In total, 14,635 MITT users were identified (mean age, 62 years). Mean PDC for MITT at 12 months was 0.37%. Mean PDC for the ICS/LABA and LAMA component at 12 months was 49% (0.49±0.31; median, 0.47) and 54% (0.54±0.33; 0.56), respectively. The proportion of adherent patients (PDC ≥0.8) at 12 months was 14% for MITT. Allowing for a 30-day gap from last day of therapy, 86% of MITT users discontinued therapy during follow-up. CONCLUSION: Patients with COPD had low adherence to and persistence with MITT in a real-world setting. Mean PDC for each single inhaler component was higher than the mean PDC observed with MITT. Reducing the number of inhalers may improve overall adherence to intended triple therapy.

Ejection fraction, B-type natriuretic peptide and risk of stroke and acute myocardial infarction among patients with heart failure.

BACKGROUND: Real-world data on the clinical outcomes of heart failure (HF) across the spectrum of ejection fraction (EF) and the prognostic value of B-type natriuretic peptide (BNP) have not been well examined. HYPOTHESIS: The real-world association between the clinical outcomes of HF and EF or BNP levels may differ across different EF or BNP values. METHODS: The Optum Integrated Claims-Clinical data (07/2009-09/2016) was used to identify adult patients with ≥1 HF diagnosis during hospitalization or emergency room visit. Three EF cohorts were formed: reduced (rEF; EF < 40%), mid-range (mrEF; EF 40%-49%), and preserved EF (pEF; EF ≥ 50%). Stratifications by BNP levels were performed using median BNP as cutoff between high vs low BNP (H-BNP vs L-BNP). RESULTS: In total, 7005 HF patients with EF measurements (2456 patients with both HF and BNP measurements) were identified. rEF patients had higher risk of stroke (hazard ratio [HR] = 1.57, P = 0.010) and acute myocardial infarction (AMI) (HR = 2.42, P < 0.001) compared to pEF patients. H-BNP was associated with a significantly higher risk of mortality (P < 0.001). rEF patients with H-BNP had a significantly higher risk of stroke than those with L-BNP. CONCLUSIONS: Patients with rEF had a significantly higher rate of stroke and AMI vs pEF patients, as did patients with H-BNP vs L-BNP. The present study is the first to show the real-world association of EF and BNP (alone and in combination) with clinical outcomes, further supporting the recommendation to use these markers in clinical practice. These results may help to guide future recommendations and improve the clinical management of HF.

Long-Term Use of Long-Acting Insulin Analogs and Breast Cancer Incidence in Women With Type 2 Diabetes.

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom's Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.

Effect of Long-Acting Insulin Analogs on the Risk of Cancer: A Systematic Review of Observational Studies.

OBJECTIVE: Observational studies examining the association between long-acting insulin analogs and cancer incidence have produced inconsistent results. We conducted a systematic review of these studies, focusing on their methodological strengths and weaknesses. RESEARCH DESIGN AND METHODS: We systematically searched MEDLINE and EMBASE from 2000 to 2014 to identify all observational studies evaluating the relationship between the long-acting insulin analogs and the risk of any and site-specific cancers (breast, colorectal, prostate). We included cohort and case-control studies published in English on insulin glargine and detemir and any cancer incidence among patients with type 1 or 2 diabetes. The methodological assessment involved the inclusion of prevalent users, inclusion of lag periods, time-related biases, and duration of follow-up between insulin initiation and cancer incidence. RESULTS: A total of 16 cohort and 3 case-control studies met our inclusion criteria. All studies evaluated insulin glargine, and four studies also examined insulin detemir. Follow-up ranged from 0.9 to 7.0 years. Thirteen of 15 studies reported no association between insulin glargine and detemir and any cancer. Four of 13 studies reported an increased risk of breast cancer with insulin glargine. In the quality assessment, 7 studies included prevalent users, 11 did not consider a lag period, 6 had time-related biases, and 16 had short (<5 years) follow-up. CONCLUSIONS: The observational studies examining the risk of cancer associated with long-acting insulin analogs have important methodological shortcomings that limit the conclusions that can be drawn. Thus, uncertainty remains, particularly for breast cancer risk.

The Use of Glyburide Compared With Other Sulfonylureas and the Risk of Cancer in Patients With Type 2 Diabetes.

OBJECTIVE: To determine whether the use of glyburide is associated with an increased risk of cancer compared with the use of other second-generation sulfonylureas among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The U.K. Clinical Practice Research Datalink was used to conduct a cohort study among 52,600 patients newly prescribed glyburide or other second-generation sulfonylureas between 1 January 1988 and 31 July 2013. A time-dependent Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs) and 95% CIs of any cancer associated with the use of glyburide compared with the use of second-generation sulfonylureas. Secondary analyses were conducted to determine whether the association varied with cumulative duration of use and cumulative dose (expressed as defined daily dose [DDD]). RESULTS: During 280,288 person-years of follow-up, 4,105 patients were given a new diagnosis of cancer (incidence rate 14.6 per 1,000 person-years). Overall, when compared with the use of other second-generation sulfonylureas, the use of glyburide was associated with a nonsignificant increased risk of any cancer (HR 1.09 [95% CI 0.98-1.22]). In secondary analyses, duration- and dose-response relationships were observed, with longer cumulative durations and cumulative doses associated with an increased risk of any cancer (>36 months: HR 1.21 [95% CI: 1.03-1.42]; >1,096 DDDs: HR 1.27 [95% CI 1.06-1.51]). CONCLUSIONS: In this population-based cohort study, longer cumulative durations and higher cumulative doses of glyburide were associated with an increased risk of cancer.

Commonly used diabetes and cardiovascular medications and cancer recurrence and cancer-specific mortality: a review of the literature.

INTRODUCTION: Cancer most commonly arises in the elderly who are often burdened with comorbidities. Medications used for treating these comorbidities may alter cancer prognosis. Understanding the impact of these medications on cancer is important in order to make effective evidence-based decisions about managing comorbidities while improving cancer outcomes. AREAS COVERED: The evidence on diabetes, statins, antihypertensive and anti-inflammatory medications and their association with cancer recurrence and cancer-specific mortality are reviewed. The strengths and limitations of the existing literature, the current state of the field and future directions are discussed. EXPERT OPINION: Metformin and aspirin were associated with a reduced risk of cancer recurrence and cancer-specific mortality. The evidence for statins and antihypertensive medications on cancer survival was inconsistent. There were few studies to suggest that any of the medication classes of interest were associated with negative effects on cancer survival. Methodological shortcomings within observational studies, such as confounding, distinguishing between use of medications pre-cancer versus post-cancer diagnosis/treatment, misclassification of exposures/outcomes, informative censoring and competing risks, must be considered. New observational studies addressing these limitations are essential. Some clinical trials are underway to further investigate the beneficial effects of these drugs and completed trials have confirmed results demonstrated in observational studies.

Index-based dietary patterns and risk of head and neck cancer in a large prospective study.

BACKGROUND: Head and neck cancer (HNC) is the seventh most common cancer worldwide. Although diet has been proposed to play an important role in HNC, few associations with diet have been convincing other than alcohol intake. Studies of dietary patterns that examine overall diets may provide broader insight than studies of individual foods. Little is known about the association between dietary patterns and risk of HNC. OBJECTIVE: We prospectively evaluated the association between 2 index-based dietary patterns [ie, the Healthy Eating Index-2005 (HEI-2005) and alternate Mediterranean Diet Score (aMED)] and risk of head and neck squamous cell carcinoma. DESIGN: We included 494,967 participants from the NIH-AARP Diet and Health study (1995-2006). HRs (95% CIs) were estimated by using Cox regression. Scores for the HEI-2005 and aMED were calculated on the basis of diet assessed by using a baseline food-frequency questionnaire. Higher scores reflected adherence to dietary recommendations for healthy eating. Our main outcome was the incidence of HNC, including cancer of the larynx, oral cavity, and orohypopharynx. RESULTS: A total of 1868 HNC cases were identified during follow-up. Higher HEI-2005 scores were associated with reduced risk of HNC in men [HR: 0.74 (95% CI: 0.61, 0.89) for highest compared with lowest quintiles; P-trend = 0.0008] and women [HR: 0.48; 95% CI: 0.33, 0.70; P-trend < 0.0001]. High aMED scores were also associated with lower HNC risk in men (HR: 0.80; 95% CI: 0.64, 1.01; P-trend = 0.002) and women (HR: 0.42; 95% CI: 0.24, 0.74; P-trend < 0.0001). Associations were similar among subsites. We did not find significant interactions between smoking and alcohol intake and each index on HNC risk. CONCLUSIONS: HEI-2005 and aMED scores were associated inversely with risk of HNC. Large interventional studies are required to assess the causality before conveying definite public health messages.

Lifestyle and dietary factors in relation to risk of chronic myeloid leukemia in the NIH-AARP Diet and Health Study.

BACKGROUND: Aside from exposure to ionizing radiation and benzene, little is known about lifestyle risk factors for chronic myeloid leukemia (CML) in the general population. METHODS: We examined the relation between lifestyle and dietary risk factors for CML in 493,188 participants (294,271 males and 198,917 females) aged 50 to 71 years who completed a baseline questionnaire in the National Institutes of Health-AARP Diet and Health Study in 1995 to 1996. Over a median of 10.5 years of follow-up, 178 incident cases of CML (139 males and 39 females) were ascertained from state registries. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for exposures of interest, adjusting for potential confounding variables. RESULTS: In multivariable analysis of all participants combined, female sex, years of education, and vigorous physical activity (HR for ≥3 times/week vs. <1 time/week 0.70; 95% CI, 0.49-0.99) were inversely associated with risk of CML, whereas smoking intensity (HR for smokers of ≥20 cigarettes per day vs. never smokers: 1.53; 95% CI, 1.03-2.27) and body mass (HR for BMI ≥ 30 vs. <25 kg/m(2) 1.46; 95% CI, 0.95-2.23) were associated with increased risk. A range of dietary factors was not associated with disease. CONCLUSIONS: This study adds to the sparse information about lifestyle factors, which affect the risk of CML in the general population. IMPACT: If these findings are confirmed, it would suggest that CML may be amenable to preventive strategies.