Drug Program Information Network Research Articles

Government Direct-to-Consumer Education to Reduce Prescription Opioid Use

Direct-to-consumer education reduces chronic sedative use. The effectiveness of this approach for prescription opioids among patients with chronic noncancer pain remains untested. To evaluate the effectiveness of a government-led educational information brochure mailed to community-dwelling, long-term opioid consumers to reduce prescription opioid use compared with usual care. This cluster randomized clinical trial was conducted from July 2018 to January 2019 in Manitoba, Canada. All adults with long-term opioid prescriptions were enrolled (n = 4225). Participants were identified via the Manitoba Drug Program Information Network. Individuals receiving palliative care or with a diagnosis of cancer or dementia were excluded. Data were analyzed from July 2019 to March 2020. Participants were clustered according to their primary care clinic and randomized to the intervention (a codesigned direct-to-consumer educational brochure sent by mail) or usual care (comparator group). The main outcome was discontinuation of opioid prescriptions at the participant level after 6 months, ascertained by pharmacy drug claims. Secondary outcomes included dose reduction (in morphine milligram equivalents [MME]) and/or therapeutic switch. Reduction in opioid use was assessed using generalized estimating equations to account for clustering, with prespecified subgroup analyses by age and sex. Analysis was intention to treat. Of 4206 participants, 2409 (57.3%) were male; mean (SD) age was 60.0 (14.4) years. Mean (SD) baseline opioid use was comparable between groups (intervention, 157.7 [179.7] MME/d; control, 153.4 [181.8] MME/d). After 6 months, 235 of 2136 participants (11.0%) in 127 clusters in the intervention group no longer filled opioid prescriptions compared with 228 of 2070 (11.0%) in 124 clusters in the comparator group (difference, 0.0%; 95% CI, -1.9% to 1.9%). More participants in the intervention group than in the control group reduced their dose (1410 [66.0%] vs 1307 [63.1%]; difference, 2.8% [95% CI, 0.0%-5.7%]). Receipt of the brochure led to greater dose reductions for participants who were male (difference, 3.9%; 95% CI, 0.1%-7.7%), aged 18 to 64 years (difference, 3.7%; 95% CI, 0.2%-7.2%), or living in urban areas (difference, 5.9%; 95% CI, 1.9%-9.9%) compared with usual care. In this cluster randomized clinical trial, no significant difference in the prevalence of opioid cessation was observed after 6 months between the intervention and usual care groups; however, the intervention resulted in more adults reducing their opioid dose compared with usual care. ClinicalTrials.gov Identifier: NCT03400384.

Polypharmacy and Potentially Inappropriate Medication Use in Older Adults With Systemic Lupus Erythematosus.

To assess the prevalence and potential risk factors for polypharmacy and prescribing of the potentially inappropriate medications, opioids and benzodiazepines/Z-drugs, in older adults with systemic lupus erythematosus (SLE). The study population comprised adults age ≥50 years meeting American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria followed at a tertiary care rheumatology clinic. Information on prescriptions filled in the 4 months preceding chart review was obtained from the Manitoba Drug Program Information Network. Clinical data, including age, sex, Charlson Comorbidity Index (CCI) score, Systemic Lupus Erythematosus Disease Activity Index 2000 score, prednisone use, SLE duration, and rural residence were abstracted from electronic medical records. Logistic regression analyses were performed to assess any association between polypharmacy (using 2 definitions: ≥5 and ≥10 medications), potentially inappropriate medication use, and clinical features. A total of 206 patients (mean age 62 years, 91% female, 36% rural) were included: 148 (72%) filled ≥5 medications, 71 (35%) filled ≥10 medications, 63 (31%) used benzodiazepines/Z-drugs, and 50 (24%) used opioids. Among the 77 patients age ≥65 years, 57 (74%) filled ≥5 medications, and 26 (34%) filled ≥10 medications, compared to 30% and 4%, respectively, of Manitobans age ≥65 years (National Prescription Drug Utilization Information System, 2016). The odds of polypharmacy were greater with prednisone use (adjusted odds ratio [OR] 3.70 [95% confidence interval (95% CI) 1.40-9.79] for ≥5 medications), CCI score (adjusted OR 1.62 [95% CI 1.20-2.17]), and rural residence (adjusted OR 2.05 [95% CI 1.01-4.18]). Odds of benzodiazepine/Z-drug use were increased with polypharmacy (adjusted OR 4.35 [95% CI 1.69-11.22]), and odds of opioid use were increased with polypharmacy (adjusted OR 6.75 [95% CI 1.93-23.69]) and CCI score (adjusted OR 1.29 [95% CI 1.08-1.54]). The prevalence of polypharmacy in this SLE cohort was higher than in the general Manitoban population. Polypharmacy is a strong marker for use of prescription benzodiazepines/Z-drugs and opioids.

Long-Acting Injectable Antipsychotics in a Prescription Claims Data Source: A Validation Study.

BackgroundThe effectiveness of long-acting injectable antipsychotics (LAIAs) has been demonstrated in studies using prescription claims data. However, the validity of claims data for LAIAs has not been established.ObjectiveWe aimed to validate date dispensed, quantity dispensed and days supplied fields in prescription claims data, and to compare claims- and medical record-derived persistence estimates.MethodsWe evaluated LAIA dispensations in the Drug Programs Information Network prescription claims database from Manitoba, Canada against a random sample of medical records. Adults with one or more LAIA prescription between April 2015 and March 2016 were eligible. Results were stratified by LAIA type (first-generation LAIA, risperidone LAI or paliperidone LAI). Persistence estimates were assessed using Kaplan–Meier survival analysis and proportion of patients covered method.ResultsClaims data had high positive predictive value, ranging from 80.0% (95% CI 51.9–95.7) to 100.0% (95% CI 89.7–100.0), but low negative predictive value, ranging from 0.0% (95% CI 0.0–2.5) to 62.5% (95% CI 40.6–81.2). Quantity dispensed and days supplied exactly matched dose and dosing interval, respectively, for 99.7% and 97.1% of risperidone LAI doses, 100.0% and 76.6% of paliperidone doses, and 8.9% and 28.3% of first-generation LAIA doses. There were no significant differences in claims-derived versus medical record-derived persistence estimates.ConclusionsQuantity dispensed and days supplied provide valid estimates of dose and dosing interval for second-generation LAIAs, but underestimated these parameters for first-generation LAIAs. However, a large proportion of medical record-confirmed doses were missing from claims data, and dose and dosing interval are underestimated in claims data.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-022-00297-4.

Leveraging policy to reduce chronic opioid use by educating and empowering community dwelling adults: a study protocol for the TAPERING randomized controlled trial

BackgroundOpioid use has risen to epidemic proportions across Canada, with increasing evidence of harms including accidental overdose and death. Policy-makers have called for effective approaches to promote opioid reduction. One promising method from deprescribing randomized trials is to empower patients through direct-to-patient education. The current trial will evaluate the effectiveness of a government-led mail-out of educational information to adult community-dwelling, chronic opioid users on the reduction of opioids compared to usual care.MethodsThis is a pragmatic, prospective, cluster randomized, parallel-arm controlled trial, comparing mailed distribution of a direct-to-patient educational brochure for chronic opioid use (intervention arm) to usual care (control arm). Eligible participants from across Manitoba, Canada, will be identified by the Provincial Drug Programs Branch within the Manitoba Health, Seniors and Active Living Department of the Manitoba Government, allocated to primary care providers, and the latter will be randomized in clusters of family medicine practices to achieve a 1:1 ratio. The primary outcome is complete cessation of opioids after 6 months assessed using Drug Program Information Network data. Secondary outcomes include ≥ 25% dose reduction in the mean morphine milligram equivalent (MME) daily dose, reduction of daily dose to < 90 mg MME, or therapeutic switch to another opioid or non-opioid medication. Data will be analyzed using intent-to-treat generalized estimating equations.DiscussionThis trial will test the efficacy of a population-based, wide-scale, government-led direct-to-patient educational initiative to drive reductions in chronic opioid use by community-dwelling adults across Manitoba.Trial RegistrationClinicalTrials.gov, ID: NCT03400384. Registered on 18 January 2018.

Hormone Use After Nonserous Epithelial Ovarian Cancer: Overall and Disease-Free Survival.

To evaluate whether hormone therapy (HT) after nonserous epithelial ovarian cancer is associated with a decrease in overall and disease-free survival. We conducted a retrospective cohort study. The Manitoba Cancer Registry and Drug Programs Information Network were searched to find all women with known nonserous epithelial ovarian, fallopian tube, or primary peritoneal cancer between 1995 and 2010 who had used HT after treatment. Women who did not receive treatment or had no follow-up were excluded. Three hundred ninety-one patients met the inclusion criteria. Seventeen patients were excluded because the patients did not receive treatment for cancer, and 17 were excluded for lack of follow-up. A total of 94 women received HT after treatment, and 263 women did not. The average age was 57.8 years. In HT users younger than 55 years of age, disease-free survival is improved according to both the multivariable landmark analysis (n=68/145, adjusted hazard ratio 0.354, 95% confidence interval [CI] 0.17-0.74, P=.006) and the time-varying Cox regression analysis (n=42/158, adjusted hazard ratio 0.212, 95% CI 0.07-0.60, P=.004) when adjusting for International Federation of Gynecology and Obstetrics stage and need for chemotherapy. There is no statistical difference in overall survival in this age group. No associations between HT use and overall survival or disease-free survival were found among women aged 55 years and older. After treatment for nonserous epithelial ovarian cancer, hormone therapy is not associated with decreased disease-free or overall survival.

Diagnosis of VTE postdischarge for major abdominal and pelvic oncologic surgery: implications for a change in practice.

Extended thromboprophylaxis after hospital discharge following cancer surgery has been shown to reduce the incidence of venous thromboembolism (VTE); however, this practice has not been universally adopted. We conducted a population-based analysis to determine the proportion of patients with symptomatic VTE diagnosed within 90 days after initial discharge following major abdominopelvic cancer surgery who might have benefited from extended thromboprophylaxis. We used the Manitoba Cancer Registry to identify patients who underwent major abdominopelvic cancer surgery between 2004 and 2009. The proportion in whom VTE was diagnosed during the initial hospital stay was determined by accessing the Hospital Separations Abstracts. The proportion in whom VTE was diagnosed after discharge was determined by examining repeat admissions within 90 days and by accessing Drug Programs Information Network records for newly prescribed anticoagulants. Detailed tumour and treatment-specific data allowed calculation of VTE predictors. Of 6612 patients identified, 106 (1.60%) had VTE diagnosed during the initial stay and 96 (1.45%) presented with VTE after discharge. Among patients in whom VTE developed after discharge, 33.3% had a pulmonary embolus, 24% had deep vein thrombosis, and 6.3% had both. Predictors of presenting with VTE after discharge within 90 days of surgery included advanced disease, presence of other complications, increased hospital resource utilization, primary tumours of noncolorectal gastrointestinal origin and age younger than 45 years. The development of VTE was an independent predictor of decreased 5-year overall survival. The cumulative incidence of VTE within 90 days of major abdominopelvic oncologic surgery was 3.01%, with about half (1.45%) having been diagnosed within 90 days after discharge.

Abstract P3-07-13: Outcomes of women with small, early-stage breast cancer in Manitoba from 1995-2011

Abstract OBJECTIVES: The objectives of this study were to describe the distribution, management, and outcomes of women with early-stage breast cancer in Manitoba during the period from 1995-2011. Specifically, we looked at tumours 1cm or smaller in size (T1mic/T1a/T1b) across the spectrum of molecular phenotypes: estrogen-receptor (ER) status, progesterone-receptor (PR) status, and human epidermal growth factor receptor 2 (HER2) status. This is the first study to evaluate these objectives in Manitoba, and will contribute significantly to the limited data of long-term outcomes for smaller-sized breast tumours. METHODS: Using the Manitoba Cancer Registry, we created a retrospective cohort of all patients with primary breast cancer of 1.0 cm or less, between 1995 and 2011. Women with previous or synchronous contralateral breast cancers were excluded. Data included patient demographics, diagnostic procedure, tumour size, nodal disease, treatment modalities (surgery, radiotherapy, hormone therapy, and chemotherapy), ER status, PR status, and HER2 status. Linkage to the Manitoba Health Drug Program Information Network (DPIN) database allowed capture of all hormonal therapies. Patient outcomes were evaluated, including risk of recurrence, overall survival and relative survival. Risk of recurrence was illustrated using cumulative incidence of recurrence, accounting for the competing risk of death. Kaplan-Meier curves were used to illustrate overall survival. The relative survival estimate was used to estimate the probability of surviving from breast cancer while controlling for differences in mortality due to other causes. RESULTS: Our study captured 2,341 women. Mean age at diagnosis was 62. ER+, PR+, and HER2+ status were 71% (11% unknown), 61.6% (11% unknown), and 8.6% (31% unknown), respectively. Clinically, 78% were Stage I disease, and by tumour size overall: T1mic 11.5%, T1a 18.9%, and T1b 69.7%. Ninety-eight percent had primary surgery, 58% had primary radiation, 48% received hormone therapy, and 16% received chemotherapy. At last follow-up, 21% of all patients were deceased. Relative survival estimates revealed that the survival of the overall cohort was not different than the general population, when comparing based on age groupings for Manitoban females. Recurrence occurred in 6.6% (156) of all cases. ER+, PR+, and HER2+ status were 63% (4% unknown), 58% (4% unknown), and 48% (5% unknown), respectively. By staging, 65% were Stage I disease and by tumour size 60% were T1b. Overall, 64% of recurrences were node-negative. For the HER2+, node-negative subpopulation at diagnosis: 21% of the T1mic group recurred, 41% of T1a recurred, and 19% of T1b recurred. In all recurrences, 39% of patients were deceased at last follow-up. CONCLUSIONS: Small, early-stage breast cancers are common and a significant proportion of patients recur. HER2-positivity appears to be an important risk factor for recurrence and may independently warrant treatment with trastuzumab, regardless of primary tumour size. Citation Format: Aly-Khan Lalani, Katherine Fradette, Rashid Ahmed, Debjani Grenier, Marshall Pitz. Outcomes of women with small, early-stage breast cancer in Manitoba from 1995-2011 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-13.

Androgen pathway manipulation and survival in patients with lung cancer.

The epidemiology of lung cancer differs between men and women. The role of androgens in lung cancer remains unclear. This study was performed to determine if exposure to androgen pathway manipulation (APM) is associated with greater survival in male patients diagnosed with lung cancer. Using a retrospective cohort design, all men diagnosed with lung cancer from January 1, 2004 to December 31, 2010 were identified from the population-based Manitoba Cancer Registry and Manitoba Health Administrative Databases. Information from the Drug Program Information Network (DPIN) was used to determine prescriptions filled for antiandrogens, 5-alpha reductase inhibitors, and gonadotropin-releasing hormone (GnRH) agonists. Multivariable Cox proportional hazards analysis with time-varying exposure variables was used to compare survival. A total of 3018 men with lung cancer were identified between 2004 and 2010. Of these, 339 (11.5%) were identified as having used a form of APM. The majority of patients received 5-alpha reductase inhibitors. Patients who received APM prior to the diagnosis of lung cancer had no significant difference in survival (HR 0.97, p = 0.69) compared to those who did not. Patients exposed to APM after their diagnosis were found to have a significantly better survival (HR 0.36, p = 0.0007), as were those exposed both before and after diagnosis (HR 0.53, p < 0.0001). In male patients diagnosed with lung cancer, exposure to APM is associated with significantly better survival when compared with no exposure. The association is only seen when some or all of the exposure has occurred after the diagnosis of lung cancer.

ED-28 * EFFECT OF VALPROIC ACID EXPOSURE ON SURVIVAL IN LOW-GRADE GLIOMA PATIENTS: A RETROSPECTIVE ANALYSIS

BACKGROUND: Recent years have seen growing interest in histone deacetylase inhibitors (HDACi) in the treatment of various cancers, including gliomas. Valproic acid (VPA), a well-known anticonvulsant, is an HDACi and has been shown to increase sensitivity of tumour cells to multiple agents in vitro and in vivo. Retrospective work in glioblastoma has suggested an overall survival (OS) benefit for patients taking VPA. We performed a retrospective analysis of low-grade glioma (LGG) diagnoses in Manitoba, Canada and prescription histories to determine whether VPA improved survival. METHODS: The Manitoba Cancer Registry was searched for all cases of glioma diagnosis dating back to 1996. We included all patients with LGG aged 18 or older. Patients were considered to have LGG if they had histological confirmation, or had neuroimaging >1 year prior to the first surgery date with a higher grade histology. Date of diagnosis was set as the date of first neuroimaging. The Drug Program Information Network database was searched for anticonvulsant prescriptions received by patients identified. Variables tested were use of VPA (with or without other anticonvulsants), use of anticonvulsants excluding VPA, and no use of any anticonvulsants. RESULTS: We identified 321 patients, 37 (12%) of whom were on VPA, 138 (43%) of whom were on other anticonvulsants excluding VPA, and 146 (45%) of whom were without anticonvulsants. Preliminary analysis reveals a 6.9 years median OS for patients taking VPA, compared to 3.1 years for those taking other anticonvulsants and 0.6 years for those taking no anticonvulsants. CONCLUSIONS: This retrospective analysis suggests that VPA lengthens OS in patients with LGG. Multivariable analysis will further evaluate this potential difference. One limitation is the inclusion of rapidly progressive lesions in the median OS analysis, despite their known poor prognosis. Further prospective work is warranted to study the utility of VPA in improving OS.

Results OF A PHYSICIAN ALERT SYSTEM FOR ANTICOAGULATION OF ATRIAL FIBRILLATION DETECTED ON CARDIAC IMPLANTED ELECTRONIC DEVICES

Results OF A PHYSICIAN ALERT SYSTEM FOR ANTICOAGULATION OF ATRIAL FIBRILLATION DETECTED ON CARDIAC IMPLANTED ELECTRONIC DEVICES

RATIONALE AND DESIGN OF THE PROGRAM FOR THE IDENTIFICATION OF “ACTIONABLE” ATRIAL FIBRILLATION (PIAAF): SYSTEMATIC IDENTIFICATION TO DETECT PREVIOUSLY UNDIAGNOSED OR UNTREATED AF IN THE COMMUNITY

strated that AF detected on cardiac implanted electronic devices (CIED) predicts a higher risk of stroke. Here we describe the results of a physician alert system for anticoagulation for AF detected on CIED. METHODS: Starting in 2013, the nurse-led pacemaker clinic at St Boniface Hospital implemented a physician alert system notifying referring physicians to the presence of AF on a CIED, and to suggest initiation of anticoagulation if CHADS2 > 1 and no contraindications. We reviewed patients who had these alerts from March 2013 to January 2014 using the pacemaker database and the St Boniface Hospital charts for demographics, stroke (CHADS2 and CHA2DS2VaSc) and bleeding (HASBLED) risk profile. We also reviewed the Manitoba Drug Program Information Network (DPIN) for prescription information regarding anticoagulation. Univariate and multivariate analysis were used to determine if risk factors were predictive of anticoagulation prescription. RESULTS: There were a total of 177 patients who had AF detected and alert produced, of which 126 had a CHADS2 > 1 (71%.) There were 72 males (57%) with a mean age of 82 9. Overall prevalence of risk factors for thromboembolism are listed in table 1. Overall 52 patients (41%) were started on anticoagulation (18 on vitamin K antagonist and 34 on non vitamin K antagonist) with the majority (39/52, 75%) started in the first 3 months. Overall there was no noticeable difference in the rates of anticoagulation for those with thromboembolism risk factors and those without (table 1) as well as for bleeding risk factors, except for prescription for ASA. On multivariate analysis, only being on ASA (OR 0.20 (0.08 0.46), and AF episodes lasting > 4 hours (OR 2.85 (1.07 7.56), p 1⁄4 0.035) were predictive of anticoagulation. CONCLUSION: In this analysis of a physician alert system for anticoagulation for patients with AF diagnosed on CIED, 41% of patients for whom alerts were produced were started on anticoagulation. There remains significant room for education with regards to anticoagulation for care providers of patients with CIED and AF. 456 RATIONALE AND DESIGN OF THE PROGRAM FOR THE IDENTIFICATION OF “ACTIONABLE” ATRIAL FIBRILLATION (PIAAF): SYSTEMATIC IDENTIFICATION TO DETECT PREVIOUSLY UNDIAGNOSED OR UNTREATED AF IN THE COMMUNITY

Abstract P1-13-04: A comparison of cardiovascular outcomes in postmenopausal women treated with aromatase inhibitors versus tamoxifen in breast cancer

Abstract OBJECTIVE: Breast cancer treatment Phase III studies show that Aromatase Inhibitors (AI) provide a longer disease free survival period compared to tamoxifen although overall survival is not consistently improved. This suggests an increase in a competing risk. The purpose of this study is to determine if there is an increase in cardiovascular morbidity and mortality in postmenopausal women treated with AI versus those treated with tamoxifen. METHODS: Using a retrospective cohort study design all postmenopausal women with breast cancer from January 1, 2002 to December 31, 2010 were identified from the Manitoba Cancer Registry (MCR). Data from these patients was requested from the Manitoba Health administrative databases for exposure, comorbidity, and outcome variables. Specifically, Drug Program Information Network (DPIN) data from 2002 to the most recent data available to determine prescriptions filled for tamoxifen and AI as a measure of exposure to these drugs. Hospital separation abstracts, physician claims data, and DPIN were used to determine comorbidity as well as new events for cardiovascular disease. Four specific groups were identified for comparison with respect to the outcomes of interest: tamoxifen exposed, AI exposed, exposure to both and no exposure. The primary end point was cardiovascular outcomes, including incident coronary heart disease and stroke. RESULTS: There were 4729 postmenopausal women diagnosed with Stage I – III breast cancer within previously defined years. The numbers for those treated with AI, Tamoxifen or both were 1590, 1015 and 607 respectively. Excluding women with preexisting comorbidity of coronary heart disease (CHD) and stroke, a competing risk regression model found that tamoxifen at 1 year of use had a statistically significantly lower rate of CHD endpoints compared to AI (p 0.040). There was no difference in stroke incidence between the two groups. CONCLUSION: Tamoxifen appears to provide a protective affect against CHD. Aromatase Inhibitors may lead to an increase in cardiovascular morbidity and mortality which may explain the lack of overall survival benefits with it's use. In the future, Tamoxifen may be preferentially used in women with a significant cardiac history. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-04.

Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n=4241), colorectal (n=3967), breast (n=4019) or prostate (n=3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.

Antiestrogen use and survival of women with non-small cell lung cancer in Manitoba, Canada.

Lung cancer is the leading cause of cancer death worldwide. Sex differences in lung cancer incidence and survival are known. Female sex is an independent good prognostic factor. Estrogens appear to play a key role in lung cancer outcomes. Accordingly, antiestrogen use may also influence survival in female non-small cell lung cancer (NSCLC) patients. In this study, we compared survival among antiestrogen users and nonusers. We performed a retrospective population-based study. Using the Manitoba Cancer Registry (MCR), we identified all women diagnosed with NSCLC from 2000 to 2007. The population-based Drug Program Information Network was accessed to establish which patients received antiestrogens. Demographic data (e.g., smoking patterns, stage, histology) were gathered from the MCR and by chart review. Survival differences between antiestrogen-exposed and not exposed groups were compared using multivariable Cox regression. Two thousand three hundred twenty women fit our patient criteria, of which 156 had received antiestrogens. Exposure to antiestrogens was associated with a significantly decreased mortality in those exposed both before and after the diagnosis of NSCLC (adjusted hazard ratio, 0.42, p = 0.0006). This association remained consistent across age and stage groups. Antiestrogen use before and after the diagnosis of NSCLC is associated with decreased mortality. This supports previous evidence that estrogens may play a key role in the biology and outcomes of NSCLC and suggests a potential therapeutic use for these agents in this disease.

Androgen deprivation therapy and survival in patients with lung cancer.

1597 Background: The epidemiology of lung cancer differs between men and women. There exists significant evidence suggesting estrogens influence the pathophysiology of lung cancer, however the role of androgens remains unclear. This study was performed to determine if exposure to androgen deprivation therapy (ADT) has an effect on survival in male patients (pts) diagnosed with lung cancer. Methods: Using the population-based Manitoba Cancer Registry and Manitoba Health Administrative Databases, all pts diagnosed with lung cancer from January 1, 2004 to December 31, 2010 were identified. Information from the Drug Program Information Network (DPIN) and the Aria electronic record at CancerCare Manitoba were used to determine prescriptions filled for anti-androgens, 5-alpha reductase inhibitors and GnRH agonists as a measure of exposure (defined as having filled at least 2 prescriptions and/or bilateral orchiectomy). Multivariable analysis with Cox proportional hazards analysis was used to compare survival. Results: A total of 3018 men with lung cancer were identified between 2004 and 2010. Of these, 339 (10%) were identified as having used a form of ADT. The majority of pts received 5-alpha reductase inhibitors (85%), the most common being finasteride (80% of total). Multivariable analysis revealed that patients who received ADT prior to the diagnosis of lung cancer had no statistically significant difference in survival (HR: 0.97 p=0.69) compared to those who did not. Patients exposed to ADT after their diagnosis were found to have a significantly better survival than those not exposed (HR 0.36 p=0.0007). This effect was also seen in those who received ADT before and after diagnosis (HR 0.53 p&lt;0.0001). Conclusions: In male pts diagnosed with lung cancer, exposure to ADT is associated with significantly better survival when compared with no exposure. This effect is only seen when some or all of the exposure has occurred after the diagnosis of lung cancer. This study supports the hypothesis that the androgen pathway plays a role in lung cancer pathophysiology, and that androgen deprivation may improve prognosis

Association Between the Use of Antibiotics and New Diagnoses of Crohn's Disease and Ulcerative Colitis

The objective of this study was to determine if the use of antibiotics 2-5 years before diagnosis was associated with the development of inflammatory bowel disease (IBD). This was a nested case-control analysis of the population-based University of Manitoba Inflammatory Bowel Disease Epidemiologic Database. A total of 2,234 subjects diagnosed with IBD between 2001 and 2008 were matched to 22,346 controls, based on age, sex, and geographic region. Antibiotic data were drawn from the Manitoba Drug Program Information Network, a comprehensive database of all prescription drugs for all Manitobans dating back to 1995. The mean age at diagnosis was 43.4 years. In all, 12% of cases had ≥3 prescriptions 2 years before the case date, compared with 7% of controls. The odds ratio for those receiving ≥3 dispensations 2 years before their study inclusion was 1.5 (95% confidence interval: 1.3,1.8; P<0.0001) of being an IBD case. This difference in ≥3 dispensations between cases and controls was fairly consistent at 3, 4, and 5 years before IBD case date. Antibiotic dispensations were associated with both Crohn's disease (CD) and ulcerative colitis (UC), with the association nominally stronger in CD cases for ≥1 and ≥2 dispensations, while the association was stronger in UC cases for ≥3 dispensations. A dose-dependent relationship between the number of antibiotic dispensations, and the risk of IBD was observed across all years investigated. Subjects diagnosed with IBD were more likely to have been prescribed antibiotics 2-5 years before their diagnosis. This possibly implicates antibiotic use as a predisposing factor in IBD etiology.

Exposure to bisphosphonates and risk of colorectal cancer

Chemoprevention is a potentially attractive strategy for decreasing the burden of colorectal cancer (CRC). Preclinical studies suggest that bisphosphonates (BPs) may have direct antitumour effects against CRC. The objective of this study was to determine the effect of exposure to BPs on the incidence of CRC. The Manitoba Cancer Registry was used to identify patients who were diagnosed with CRC from 2000 to 2009 who had been living in Manitoba for at least 5 years before diagnosis (cases). Each case was matched to 10 controls of similar age, sex, and duration of residence in Manitoba using incidence density sampling. Exposure to BPs was determined using the provincial Drug Program Information Network database. Conditional logistic regression analysis was performed to determine the effect of exposure to BPs on CRC incidence with adjustment for health care use, medical procedures (including lower gastrointestinal endoscopy), socioeconomic status, and pre-existing health conditions. In total, 5425 patients with CRC were matched to 54,242 controls. In the multivariate analysis, exposure to BPs was associated with a reduction in the risk of CRC (2-13 BP prescriptions over ≥5 years: odds ratio [OR] 0.84; 95% confidence interval [CI], 0.71-1.00; ≥14 BP prescriptions over ≥5 years: OR, 0.78; 95% CI, 0.65-0.94). When the effect of specific BP agents was evaluated, the effect was significant only for exposure to risedronic acid (OR, 0.50; 95% CI, 0.30-0.85). There was no significant effect of increasing duration or cumulative dose of alendronic acid. The results from this study suggested that exposure to BPs, especially risedronic acid, may be associated with a decreased risk of developing CRC.

Association Between the Use of Antibiotics in the First Year of Life and Pediatric Inflammatory Bowel Disease

The development of commensal flora in infants has been shown to be sensitive to antibiotic use. Altered intestinal flora is thought to contribute to the etiology of inflammatory bowel disease (IBD), an idiopathic chronic condition. We aimed to determine if early use of antibiotics was associated with the development of IBD in childhood. Nested case-control analysis of the population-based University of Manitoba Inflammatory Bowel Disease Epidemiologic Database was carried out. IBD status was determined from a validated administrative database definition. A total of 36 subjects diagnosed between 1996 and 2008 were matched to 360 controls, on the basis of age, sex, and geographic region. Antibiotic data were drawn from the Manitoba Drug Program Information Network, a comprehensive population-based database of all prescription drugs for all Manitobans dating back to 1995. Antibiotic use in the first year of life was compared between IBD cases and controls. The mean age at IBD diagnosis was 8.4 years. Twenty-one cases (58%) had one or more antibiotic dispensations in their first year of life compared with 39% of controls. Crohn's disease was diagnosed in 75% of IBD cases. Those receiving one or more dispensations of antibiotics were at 2.9 times the odds (95% confidence interval: 1.2, 7.0) of being an IBD case. Subjects diagnosed with IBD in childhood are more likely to have used antibiotics in their first year of life.

This Month in Gastroenterology

This Month in Gastroenterology

Utilization and Costs of Antipsychotic Agents: A Canadian Population-Based Study, 1996–2006

This study evaluated the prescribing patterns and costs for antipsychotic agents in the population of the Canadian province of Manitoba over the past decade. A population-based study of antipsychotic utilization and costs was conducted on data collected from the administrative databases of the Manitoba Population Health Data Repository and the Statistics Canada census between index years 1996 and 2006 (April 1, 1995, through March 31, 2006). The total annual number of antipsychotic prescriptions dispensed in Manitoba increased by 227% between 1996 and 2006, and the prevalence of antipsychotic users increased by 62% over the same time interval. The fastest-growing segment of antipsychotic users in Manitoba appears to be young males, who increased from .16% in 1996 to .88% in 2006. The highest numbers of prescriptions were reported for schizophrenia, dementia, and conduct disorder. Annual expenditures for antipsychotics increased from $1.7 million in 1996 to $22.0 million in 2006 (expenditures are in Canadian dollars). The cost of second-generation agents reached 80% of total antipsychotic expenditures in 2006; risperidone was the most prescribed agent in all age groups of patients. The per-patient annual cost of antipsychotic pharmacotherapy increased by approximately 680% between 1996 and 2006 in Manitoba. The number of antipsychotic prescriptions and the prevalence of users of antipsychotic medications increased significantly in Manitoba over the study period, despite a steady-state population of approximately 1.2 million. Incremental costs relative to the use of antipsychotic medications can be explained by the market penetration of the second-generation agents and their expanded use in the treatment of various diagnoses.