Aims
Both acute pancreatitis (AP) and pancreatic cancer (PC) have been areas of focus for studies of incretin drugs. This 5‐year prospective cohort study aimed to quantify possible associations ...between liraglutide and risk of AP and PC as compared to other antidiabetic drugs (ADs).
Materials and methods
Patients initiating liraglutide or other ADs who were enrolled in a US health plan (2010‐2014) were included. Comparisons of AP and PC incidence rates were made between matched cohorts of liraglutide initiators and initiators of other ADs. Adjudicated AP cases and algorithm‐based PC cases were identified. Propensity score‐matched intention‐to‐treat (ITT) and time‐on‐drug (TOD) analyses were completed using Poisson regression. A latency analysis was performed for PC.
Results
Median follow‐up was 405 days for AP cohorts (9995 liraglutide, 1:1 matched to all comparators) and 503 days for PC cohorts (35 163 liraglutide, 1:1 matched to all comparators). In the primary AP analysis, “current” use of liraglutide was not significantly associated with elevated risk across comparators (all comparators relative risk RR = 1.2; 95% confidence interval CI, 0.6‐2.3). ITT results were similar where, in the primary analysis, no RRs were significantly associated with PC (all comparators RR = 0.7; 95% CI, 0.3‐1.4); latency and TOD analyses did not alter findings. There was no evidence of a dose‐response effect.
Conclusions
Liraglutide was not associated with an increased risk of AP or PC, although risk estimates were more variable for AP, and numbers of cases for both outcomes were limited because of the rarity of outcomes.
Objective
To use propensity score methods to control for confounding by indication in the association between labour induction and caesarean delivery.
Design
Cross‐sectional analysis of ...administrative hospital discharge data supplemented by medical record information.
Setting
Fourteen US member hospitals of the National Perinatal Information Center.
Sample
A cohort of 166 559 singleton liveborn deliveries in the period 2007–2012.
Methods
We used propensity scores (PSs) to balance 83 covariates between induced and non‐induced women, and compared estimates with traditional covariate adjustment. We estimated PSs for labour induction versus expectant management of pregnancy each week from 34 to 42 weeks of gestation. We estimated risk ratios (RRs) for the association between labour induction and primary caesarean delivery from models with no adjustment, traditional adjustment of five covariates, matched PS, and adjustment for continuous PS.
Main outcome measure
Caesarean delivery in current or subsequent week of gestation.
Results
In crude models labour induction increased the risk of caesarean delivery in all weeks (RR 1.06–1.52), excepting 39 weeks of gestation (RR 0.89). After matching on PS, the analysis showed a significantly decreased risk of caesarean delivery with labour induction during weeks 35–39 (RR 0.77–0.92), and a significantly elevated risk at weeks 40 (RR 1.22) and 41 (RR 1.39). Traditional covariate and PS adjustment resulted in RRs between those from crude and PS‐matched models.
Conclusions
There is evidence of considerable confounding by indication in the association of labour induction and caesarean delivery, particularly for preterm deliveries. Using PS methods, we found a reduced risk of caesarean delivery with labour induction before 40 weeks of gestation, and an elevated risk for weeks 40–42.
Tweetable
With confounding adjustment, labour induction does not increase the risk of caesarean at 34–39 weeks of gestation.
Tweetable
With confounding adjustment, labour induction does not increase the risk of caesarean at 34–39 weeks of gestation.
We quantified transdermal fentanyl prescribing in elderly nursing home residents without prior opioid use or persistent pain, and the association of individual and facility traits with opioid-naïve ...prescribing.
Cross-sectional study.
Linked Minimum Data Set (MDS) assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims.
From a cross-section of all long-stay US nursing home residents in 2008 with an MDS assessment and Medicare Part D enrollment, we identified individuals (≥65 years old) who initiated transdermal fentanyl, excluding those with Alzheimer disease, severe cognitive impairment, cancer, or receipt of hospice care.
We used Medicare Part D to select beneficiaries initiating transdermal fentanyl in 2008 and determined whether they were "opioid-naïve," defined as no opioid dispensing during the previous 60 days. We obtained resident and facility characteristics from MDS and OSCAR records and defined persistent pain as moderate-to-severe, daily pain on consecutive MDS assessments at least 90 days apart. We estimated associations of patient and facility attributes and opioid-naïve fentanyl initiation using multilevel mixed effects logistic regression modeling.
Among 17,052 residents initiating transdermal fentanyl, 6190 (36.3%) were opioid-naïve and 15,659 (91.8%) did not have persistent pain. In the regression analysis with adjustments, residents who were older (ages ≥95 odds ratio OR 1.69, 95% confidence interval CI 1.46-1.95) or more cognitively impaired (moderate-to-severe cognitive impairment, OR 1.99, 95% CI 1.73-2.29) were more likely to initiate transdermal fentanyl without prior opioid use.
Most nursing home residents initiating transdermal fentanyl did not have persistent pain and many were opioid-naïve. Changes in prescribing practices may be necessary to ensure Food and Drug Administration warnings are followed, particularly for vulnerable subgroups, such as the cognitively impaired.
Quantify association between the glucagon-like peptide-1 receptor agonist liraglutide and risk of thyroid cancer (TC) compared to other antidiabetics.
Initiators of liraglutide, exenatide, metformin, ...pioglitazone or groups of dipeptidyl peptidase-4 inhibitors or sulfonylureas were identified in a US health plan (2010-2014) and followed for a median of 17 months. Thyroid cancer cases during follow-up were identified via a validated algorithm. Incidence rates of TC among liraglutide and comparators were assessed using relative risks estimated within propensity score-matched cohorts using intention to treat (ITT) and time on drug analyses. Latency effects and potential surveillance bias were evaluated.
Relative risks from ITT analyses ranged from 1.00 (95% confidence interval (CI) 0.56-1.79) versus metformin to 1.70 (95% CI 1.03-2.81) versus all comparators excluding exenatide. Effect estimates from latency analyses were slightly attenuated. Time on drug analyses suggested no increased risk for either longer duration or higher cumulative dose of liraglutide. Medical record review found 85% were papillary or a follicular variant of papillary or both; 46% were microcarcinomas (≤10 millimeters), which were more prevalent in the liraglutide cohort (67% versus 43% in all comparators).
Relative risks were elevated for several comparisons, which should be interpreted cautiously because of potential residual confounding and surveillance bias. Liraglutide cases had smaller thyroid nodules and shorter time-to-diagnosis, suggesting increased surveillance for TC among liraglutide initiators, especially shortly after the drug´s approval. After adjusting the primary analyses (ITT) for latency, no significant elevated risk of TC was observed among liraglutide initiators.
Objectives Pediatric guidelines in 2008 and 2011 recommended lipid lowering therapy in children ≥8 years of age with high-risk cardiovascular conditions, such as familial hypercholesterolemia (FH). ...Our objective was to describe the patterns and predictors of lipid lowering therapy initiation in commercially insured children between 2005 and 2010. Study design Using commercial health plan data on children ages 8-20 years from 2004-2010, we estimated rates of lipid lowering therapy initiation overall and stratified by age. Using a nested case-control design, we used multivariable logistic regression to identify temporal, demographic, clinical, and health utilization characteristics associated with lipid lowering therapy initiation. Results Among >13 million children, 665 initiated lipid lowering therapy for an incidence rate 2.6/100 000 person-years (PY). Incidence rates were highest in 2005 (4.1/100 000 PY) and 2008 (3.9/100 000 PY), with no discernable secular trend. Rates of lipid lowering therapy initiation were significantly greater in children ≥15 years of age (OR 2.9 95% CI 5.2-13.0), males (2.1 1.7-2.4), and those with a diagnosis of FH (165.2 129.0-211.6), other dyslipidemia (175.5 143.2-215.3), diabetes type I (7.7 4.7-12.4), diabetes type II (13.6 8.5-21.7), hypertension (8.1 4.9-13.3), obesity (7.8 4.7-12.7), and ≥5 outpatient visits (1.5 1.2-1.7), and children with dispensing of ≥2 nonlipid lowering therapy prescriptions were less likely to initiate lipid lowering therapy (0.2 0.2-0.3). Conclusions Despite new guidelines, lipid lowering therapy initiation in children is low and has not increased through 2010. Although diagnosis of FH and other dyslipidemias was associated with higher probability of lipid lowering therapy initiation, our findings suggest lipid lowering therapy is underutilized in this population given the prevalence of these disorders.
Abstract Purpose Evidence of the impact of labor induction on cesarean delivery (CD) remains inconclusive because of differing methodological approaches. A spontaneous labor comparison group ...describes patterns retrospectively, whereas an expectant management comparison group prospectively evaluates a decision to induce. We examined the influence of comparison group on the association between labor induction and CD. Methods We studied 166,559 mother-newborn dyads from 14 National Perinatal Information Center member hospitals, 2007–2012. We included singleton births 34–42 completed weeks' gestation and excluded women with contraindications to vaginal delivery. We calculated risk ratios (RR) adjusted for hypertensive and diabetic disorders, intrauterine growth restriction, parity, and maternal age. Results When comparing induction to spontaneous labor, induction had significantly lower risk for CD at weeks 34–35 (adjusted RR 95% confidence interval (CI): 0.6 0.5, 0.7 for week 34 and 0.7 0.6, 0.8 for week 35) and higher risk at weeks 37–41 (adjusted RRs 95% CIs: 1.8 1.6, 2.1, 2.1 1.9, 2.2, 1.8 1.7, 1.9, 1.9 1.8, 2.0, and 1.6 1.5, 1.7, respectively). When comparing induction to expectant management, adjusted RRs 95% CIs were significantly below 1.0 for week 34 (0.8 0.7, 0.9), week 36 (0.9 0.8, 0.9), and week 37 (0.9 0.8, 0.9), and were only elevated at week 40 (1.4 1.3, 1.4) and week 41 (1.4 1.3, 1.5). Conclusions Using two different methodological approaches with the same sample, we confirm that comparing labor induction to spontaneous onset of labor, instead of expectant management of pregnancy, does not fully inform clinical practice and may lead to an exaggerated estimate of the risk of CD.
Post-marketing safety studies of medicines often rely on administrative claims databases to identify adverse outcomes following drug exposure. Valid ascertainment of outcomes is essential for ...accurate results. We aim to quantify the validity of diagnostic codes for serious hypocalcemia and dermatologic adverse events from insurance claims data among women with postmenopausal osteoporosis (PMO).
We identified potential cases of serious hypocalcemia and dermatologic events through ICD-9 diagnosis codes among women with PMO within claims from a large US healthcare insurer (June 2005-May 2010). A physician adjudicated potential hypocalcemic and dermatologic events identified from the primary position on emergency department (ED) or inpatient claims through medical record review. Positive predictive values (PPVs) and 95% confidence intervals (CIs) quantified the fraction of potential cases that were confirmed.
Among 165,729 patients with PMO, medical charts were obtained for 40 of 55 (73%) potential hypocalcemia cases; 16 were confirmed (PPV 40%, 95% CI 25-57%). The PPV was higher for ED than inpatient claims (82 vs. 24%). Among 265 potential dermatologic events (primarily urticaria or rash), we obtained 184 (69%) charts and confirmed 128 (PPV 70%, 95% CI 62-76%). The PPV was higher for ED than inpatient claims (77 vs. 39%).
Diagnostic codes for hypocalcemia and dermatologic events may be sufficient to identify events giving rise to emergency care, but are less accurate for identifying events within hospitalizations.
Abstract Purpose The amount of immortal time bias in studies with nonfatal outcomes is unclear. To quantify the magnitude of bias from mishandling of immortal person-time in studies of nonfatal ...outcomes. Methods We derived formulas for quantifying bias from misclassified or excluded immortal person-time in settings with nonfatal outcomes, assuming a constant rate of outcome. In the situation of misclassified or excluded immortal person-time, the quantification includes the immortal time and corresponding events mistakenly attributed to the exposed group (misclassified) or excluded from study (excluded) that must be attributed to the comparison group. Results With misclassified immortal person-time, the magnitude of bias varies according to the incidence rate ratio of immortal time and comparison group as well as the rate ratio of immortal time and exposed group: toward null for both ratios less than 1, no bias for both ratios equal to 1, away from null for both ratios greater than 1. For one ratio less than 1 and the other greater than 1, the direction and magnitude of bias can be obtained from the formula provided. With excluded immortal person-time, the magnitude of bias is associated with the incidence rate ratio of immortal time and comparison group: toward null for the ratio less than 1, no bias for the ratio equal to 1, and away from null for the ratio greater than 1. Conclusions Bias due to immortal person-time in studies with nonfatal outcomes can vary widely and can be quantified under assumptions that apply to many studies.
Summary Objective To describe the reproducibility and validity of six different measurement techniques for knee subchondral bone mineral density (sBMD). Methods A consecutive sample of 50 male and ...female participants from a population-based longitudinal study had sBMD assessed using dual energy X-ray absorptiometry scans. Anthropometric, knee pain, cartilage and bone measures by magnetic resonance imaging and radiographic osteoarthritis (OA) were assessed. The six methods were defined as: (1) the midpoint of one intercondylar spine, across the tibial surface and descending 10 mm; from the midpoint of the two intercondylar spines (2) the top of the spine descending 20 mm, (3) 10–20 mm beneath the top of the spine; from the tibial surface descending, (4) 10 mm, (5) 15 mm, and (6) 20 mm. Results All six methods had excellent reproducibility (intra-class correlation coefficient 0.98–1.00). sBMD was higher in males (methods 2–4) and higher in those with medial tibial osteophytes (methods 1, 3 and 4). Medial tibial cartilage defects and overall cartilage defects correlated with sBMD (methods 3 and 4). Method 2, which includes the intercondylar spine, correlated with medial tibial bone size. Measuring sBMD using methods 3 and 4 produced the greatest number of associations with joint features of OA. Conclusions These preliminary results need confirmation in larger longitudinal samples but suggest that sBMD can be accurately measured and plays a role in knee OA. Methods 3 and 4 had the best concurrent validity; however, method 2 adds additional information on tibial bone size, suggesting that two measures are necessary in clinical studies.
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