Effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on colorectal cancer incidence and its precursors

Incretin-based antihyperglycemic therapies increase intestinal mucosal expansion and polyp growth in mouse models. We aimed to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1ra) initiation on colorectal cancer incidence

Gender Disparities in Surgical Treatment of Axis Fractures in Older Adults

Study Design: Retrospective cohort study. Objectives: Gender appears to play in important role in surgical outcomes following acute cervical spine trauma, with current literature suggesting males have a significantly higher mortality following spine surgery. However, no well-adjusted population-based studies of gender disparities in incidence and outcomes of spine surgery following acute traumatic axis injuries exist to our knowledge. We hypothesized that females would receive surgery less often than males, but males would have a higher 1-year mortality following isolated traumatic axis fractures. Methods: We performed a retrospective cohort study using Medicare claims data that identified US citizens aged 65 and older with ICD-9 (International Classification of Diseases, Ninth Revision) code diagnosis corresponding to isolated acute traumatic axis fracture between 2007 and 2014. Our primary outcome was defined as cumulative incidence of surgical treatment, and our secondary outcome was 1-year mortality. Propensity weighted analysis was performed to balance covariates between genders. Our institutional review board approved the study (IRB #16-0533). Results: There was no difference in incidence of surgery between males and females following acute isolated traumatic axis fractures (7.4 and 7.5 per 100 fractures, respectively). Males had significantly higher 1-year weighted mortality overall (41.7 and 28.9 per 100 fractures, respectively, P < .001). Conclusion: Our well-adjusted data suggest there was no significant gender disparity in incidence of surgical treatment over the study period. The data also support previous observations that males have worse outcomes in comparison to females in the setting of axis fractures and spinal trauma regardless of surgical intervention

Considerations for observational study design: Comparing the evidence of opioid use between electronic health records and insurance claims

Purpose: Pharmacoepidemiology studies often use insurance claims and/or electronic health records (EHR) to capture information about medication exposure. The choice between these data sources has important implications. Methods: We linked EHR from a large academic health system (2015-2017) to Medicare insurance claims for patients undergoing surgery. Drug utilization was characterized based on medication order dates in the EHR, and prescription fill dates in Medicare claims. We compared opioid use documented in EHR orders to prescription claims in four time periods: 1) Baseline (182 days before surgery); 2) Perioperative period; 3) Discharge date; 4) Follow-up (90 days after surgery). Results: We identified 11 128 patients undergoing surgery. During baseline, 34.4% (EHR) versus 44.1% (claims) had evidence of opioid use, and 56.9% of all baseline use was reflected only in one data source. During the perioperative period, 78.8% (EHR) versus 47.6% (claims) had evidence of use. On the day of discharge, 59.6% (EHR) versus 45.5% (claims) had evidence of use, and 51.8% of all discharge use was reflected only in one data source. During follow-up, 4.3% (EHR) versus 10.4% (claims) were identified with prolonged opioid use following surgery with 81.4% of all prolonged use reflected only in one data source. Conclusions: When characterizing opioid exposure, we found substantial discrepancies between EHR medication orders and prescription claims data. In all time periods assessed, most patients' use was reflected only in the EHR, or only in the claims, not both. The potential for misclassification of drug utilization must be evaluated carefully, and choice of data source may have large impacts on key study design elements

Antidepressant Dose, Age, and the Risk of Deliberate Self-harm

IMPORTANCE A comprehensive meta-analysis of randomized trial data suggests that suicidal behavior is twice as likely when children and young adults are randomized to antidepressants compared with when they are randomized to placebo. Drug-related risk was not elevated for adults older than 24 years. To our knowledge, no study to date has examined whether the risk of suicidal behavior is related to antidepressant dose, and if so, whether risk depends on a patient's age. OBJECTIVE To assess the risk of deliberate self-harm by antidepressant dose, by age group. DESIGN, SETTING, AND PARTICIPANTS This was a propensity score-matched cohort study using population-based health care utilization data from 162 625 US residents with depression ages 10 to 64 years who initiated antidepressant therapy with selective serotonin reuptake inhibitors at modal or at higher than modal doses from January 1,1998, through December 31.2010. MAIN OUTCOMES AND MEASURES International Classification of Diseases, Ninth Revision (ICD-9) external cause of injury codes E950.x-E958.x (deliberate self-harm). RESULTS The rate of deliberate self-harm among children and adults 24 years of age or younger who initiated high-dose therapy was approximately twice as high as among matched patients initiating modal-dose therapy (hazard ratio [HR], 2.2 [95% Cl, 1.6-3.0]), corresponding to approximately 1 additional event for every 150 such patients treated with high-dose (instead of modal-dose) therapy. For adults 25 to 64 years of age, the absolute risk of suicidal behavior was far lower and the effective risk difference null (HR, 1.2 [95% CI, 0.8-1.9]). CONCLUSIONS AND RELEVANCE Children and young adults initiating therapy with antidepressants at high-therapeutic (rather than modal-therapeutic) doses seem to be at heightened risk of deliberate self-harm. Considered in light of recent meta-analyses concluding that the efficacy of antidepressant therapy for youth seems to be modest, and separate evidence that antidepressant dose is generally unrelated to therapeutic efficacy, our findings offer clinicians an additional incentive to avoid initiating pharmacotherapy at high-therapeutic doses and to closely monitor patients starting antidepressants, especially youth, for several months

More realistic power estimation for new user, active comparator studies: an empirical example: New User Design Power Estimation Considerations

Pharmacoepidemiologic studies are often expected to be sufficiently powered to study rare outcomes, but there is sequential loss of power with implementation of study design options minimizing bias. We illustrate this using a study comparing pancreatic cancer incidence after initiating dipeptidyl-peptidase-4 inhibitors (DPP-4i) versus thiazolidinediones or sulfonylureas

Comparison of diagnostic evaluations for cough among initiators of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: Diagnostic Workup in Antihypertensive Drug Initiators

Differential diagnostic evaluation associated with a drug may bias effect estimates due to an increased detection of preclinical outcomes. Persistent cough is a common side effect with angiotensin-converting enzyme inhibitors (ACEI) and we hypothesized that ACEI initiators would undergo more diagnostic evaluations, potentially leading to diagnosis of preclinical lung cancer. We compared the incidence of cough-related diagnostic evaluations and lung cancer among ACEI versus angiotensin receptor blockers (ARB) initiators

Cancer Incidence Among Those Initiating Insulin Therapy With Glargine Versus Human NPH Insulin

OBJECTIVE To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer. RESEARCH DESIGN AND METHODS We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality. RESULTS More patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer. The overall HR was 1.12 (95% CI 0.95–1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses. CONCLUSIONS Patients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing

Sling revision/removal for mesh erosion and urinary retention: long-term risk and predictors

To estimate the long-term risk of sling revision/removal after an initial sling and to assess indications (mesh erosion and urinary retention) and predictors of sling revision/removal

Lifetime Risk of Stress Urinary Incontinence or Pelvic Organ Prolapse Surgery

To estimate the lifetime risk of stress incontinence, pelvic organ prolapse surgery, or both using current, population-based surgical rates from 2007–2011

Estimating the Impact of Prescribing Limits On Prolonged Opioid Use Following Surgery

Background: In response to concerns about opioid addiction, some states now limit the days supplied (DS) for initial postoperative prescriptions. However, few studies have examined the impact of these policy changes on prolonged opioid use in the population. Objectives: To a) examine the gradient of risk of prolonged postsurgical opioid use based on the initial prescription duration, and b) estimate the potential impact of varying prescribing limits on risk of prolonged postsurgical opioid use. Conclusions: We illustrate a method to examine potential impacts of prescribing limits. While risk of prolonged postsurgical opioid use increased as patients received larger initial DS, the number of prolonged use cases theoretically preventable by prescribing limits differed by orders of magnitude depending on the number of patients above the proposed limit. While most laws focus on DS limits, results for quantity and dosage dispensed show similar trends and will also be presented, along with procedure specific (knee arthroplasty, hernia repair, cholecystectomy) results