Publications

BACKGROUND: Achalasia is an esophageal motor disorder that leads to swallowing dysfunction and weight loss. Nutritional risk in achalasia patients is not well defined.

AIMS: The aims of this study were to define baseline body mass index (BMI), changes in weight, and nutritional risk over time in a large cohort of achalasia patients.

METHODS: This was a retrospective cohort study of achalasia patients at a tertiary care center with documented BMI, symptom severity as per Eckardt score, and nutritional risk assessment as per the Malnutrition Universal Screening Tool, which considers BMI, degree of recent weight loss, and acuity of disease.

RESULTS: Among the 337 patients presenting for achalasia management, 179 had confirmed disease. Upon presentation 69.8% of patients were classified as overweight or obese. Using the Malnutrition Universal Screening Tool, we found 50% of patients to be at moderate or high risk for malnutrition at presentation. Eckardt score (OR 1.15, 95% CI 1.05-1.26), duration of disease (OR for each additional month 1.04, 95% CI 1.01-1.08), and female gender (OR 1.76, 95% CI 1.02-3.03) were independent predictors of increased risk for malnutrition. Nutrition risk score decreased after therapy in 93.3% of patients.

CONCLUSIONS: Despite a high prevalence of overweight and obese status in achalasia patients, many are at risk of developing nutritional complications secondary to rapid weight loss. This risk frequently resolves post-treatment. Regardless of baseline BMI, we recommend all patients undergo nutritional assessment to identify high-risk patients who may benefit from dietary intervention and expedited therapy.

BACKGROUND: Preliminary data suggest that treatment optimization can reverse immunogenicity and regain response in patients with IBD and secondary loss of response (SLR) to anti-TNF therapy due to antidrug antibodies. However, data regarding the long-term outcome of these patients are scarce.

AIMS: We aimed to investigate drug retention in IBD patients of whom infliximab was optimized to overcome immunogenicity and variables associated with drug retention.

METHODS: This was a retrospective, multicenter study of consecutive IBD patients with antibodies to infliximab (ATI), based on either proactive or reactive therapeutic drug monitoring, who underwent infliximab optimization (increasing dose, shortening interval, adding an immunomodulator, or combination) to overcome immunogenicity from September 2012 to July 2015; they were followed through December 2015. ATI were analyzed using the drug-tolerant Prometheus homogeneous mobility shift assay. Drug retention was defined as no need for drug discontinuation due to SLR or serious adverse event.

RESULTS: Our cohort consisted of 22 patients (Crohn's disease, n = 15). At the end of follow-up [median, (IQR): 17.3 (10.5-32.8) months] 77% (15/22) of patients were still on drug. Univariable Cox proportional hazards regression analysis identified first detectable ATI titer as the only variable associated with drug retention (HR: 0.89; 95% CI: 0.82-0.98, p = 0.016). Receiver-operating characteristic analysis identified an ATI titer < 8.8 U/mL associated with drug retention.

CONCLUSIONS: In real-life clinical practice, optimization of infliximab therapy can prevent drug discontinuation in approximately 3/4 of patients with ATI, especially in those with low titers. Large prospective studies are needed to confirm these data.

BACKGROUND: The benefit of surveillance after curative cystectomy in bladder cancer is unproven, but might be justified if detection of asymptomatic recurrence improves survival. Previous studies showing a benefit of surveillance might have been affected by lead-time or length-time bias.

MATERIALS AND METHODS: We conducted a retrospective cohort study among 463 cystectomy patients at the University of Pennsylvania. Patients were followed according to a standardized protocol and classified according to asymptomatic or symptomatic recurrence detection. Primary outcome was all-cause mortality. Adjusted Cox regression models were used to assess the effect of mode of recurrence on survival from time of cystectomy (model 1) and time of recurrence (model 2) to account for lead and length time.

RESULTS: One hundred ninety-seven patients (42.5%) recurred; 71 were asymptomatic (36.0%), 107 were symptomatic (54.3%), and 19 (9.6%) were unknown. Relative to patients with asymptomatic recurrence, patients with symptomatic recurrence had significantly increased risk of death (model 1: hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.07-2.61; model 2: HR, 1.74, 95% CI, 1.13-2.69) and had lower 1-year overall survival from time of recurrence (29.37% vs. 55.66%). Symptomatic patients were diagnosed with recurrence a median of 1.7 months before asymptomatic patients, yet their median survival from recurrence was 8.2 months less.

CONCLUSION: Symptomatic recurrence is associated with worse outcomes than asymptomatic recurrence, which cannot be explained by lead- or length-time bias. Similar methods to account for these biases should be considered in studies of cancer surveillance. Shortening surveillance intervals might allow for detection of more recurrences in an asymptomatic phase.

BACKGROUND & AIMS: Although recurrent diverticular hemorrhage is common, its incidence and risk factors have not been measured outside of small institutional cohorts. We analyzed the incidence of and risk factors for recurrent diverticular hemorrhage and whether discontinuing anticoagulation after diverticular hemorrhage is associated with ischemic stroke.

METHODS: We performed a retrospective cohort study of patients enrolled in the OptumInsight Clinformatics database from 2000 through 2016. Incidence rates for initial and recurrent diverticular hemorrhage were calculated by identifying patients who had hospitalizations with a primary discharge diagnosis consistent with diverticular hemorrhage. The hazard ratios of second diverticular hemorrhage associated with anticoagulants or platelet aggregation inhibitors were calculated using Cox proportional hazards regression adjusted for demographics, comorbidities, and medication use. The hazard ratio for ischemic stroke among patients who discontinued anticoagulation after diverticular hemorrhage was calculated similarly.

RESULTS: In the cohort analyzed, 14,925 patients had an initial diverticular hemorrhage; 1368 of these patients had a second episode. The unstandardized incidence rates of initial and second diverticular hemorrhage were 10.9 per 100,000 person-years (95% confidence interval [CI] 10.7-11.0) and 3625.6 per 100,000 person-years (95% CI 3436.0-3823.0). Platelet aggregation inhibitors were associated with second episodes of diverticular hemorrhage (hazard ratio 1.47; 95% CI 1.15-1.88), whereas all classes of anticoagulation agents were not associated. Among patients with a potential indication for stroke prophylaxis, those who discontinued anticoagulation after the diverticular hemorrhage had an increased hazard of ischemic stroke (hazard ratio 1.93; 95% CI 1.17-3.19).

CONCLUSIONS: In this retrospective cohort study, platelet aggregation inhibitors, but not anticoagulants, were associated with recurrent diverticular hemorrhage. Discontinuing anticoagulation was associated with increased hazard for ischemic stroke.

OBJECTIVE: Observational studies analyzing multiple exposures simultaneously have been limited by difficulty distinguishing relevant results from chance associations due to poor specificity. Set-based methods have been successfully used in genomics to improve signal-to-noise ratio. We present and demonstrate medication class enrichment analysis (MCEA), a signal-to-noise enhancement algorithm for observational data inspired by set-based methods.

MATERIALS AND METHODS: We used The Health Improvement Network database to study medications associated with Clostridium difficile infection (CDI). We performed case-control studies for each medication in The Health Improvement Network to obtain odds ratios (ORs) for association with CDI. We then calculated the association of each pharmacologic class with CDI using logistic regression and MCEA. We also performed simulation studies in which we assessed the sensitivity and specificity of logistic regression compared to MCEA for ORs 0.1-2.0.

RESULTS: When analyzing pharmacologic classes using logistic regression, 47 of 110 pharmacologic classes were identified as associated with CDI. When analyzing pharmacologic classes using MCEA, only fluoroquinolones, a class of antibiotics with biologically confirmed causation, and heparin products were associated with CDI. In simulation, MCEA had superior specificity compared to logistic regression across all tested effect sizes and equal or better sensitivity for all effect sizes besides those close to null.

DISCUSSION: Although these results demonstrate the promise of MCEA, additional studies that include inpatient administered medications are necessary for validation of the algorithm.

CONCLUSIONS: In clinical and simulation studies, MCEA demonstrated superior sensitivity and specificity for identifying pharmacologic classes associated with CDI compared to logistic regression.

BACKGROUND AND AIMS: Reactive testing has emerged as the new standard of care for managing loss of response to infliximab in inflammatory bowel disease [IBD]. Recent data suggest that proactive infliximab monitoring is associated with better therapeutic outcomes in IBD. Nevertheless, there are no data regarding the clinical utility of proactive infliximab monitoring after first reactive testing. We aimed to evaluate long-term outcomes of proactive infliximab monitoring following reactive testing compared with reactive testing alone in patients with IBD.

METHODS: This was a retrospective multicenter cohort study of consecutive IBD patients on infliximab maintenance therapy receiving a first reactive testing between September 2006 and January 2015. Patients were divided into two groups; Group A [proactive infliximab monitoring after reactive testing] and Group B [reactive testing alone]. Patients were followed through December 2015. Time-to-event analysis for treatment failure and IBD-related surgery and hospitalization was performed. Treatment failure was defined as drug discontinuation due to either loss of response or serious adverse event.

RESULTS: The study population consisted of 102 [n = 70, 69% with CD] patients [Group A, n = 33 and Group B, n = 69] who were followed for (median, interquartile range [IQR]) 2.7 [1.4-3.8] years. Multiple Cox regression analysis identified proactive following reactive TDM as independently associated with less treatment failure (hazard ratio [HR] 0.15; 95% confidence interval [CI] 0.05-0.51; p = 0.002) and fewer IBD-related hospitalizations [HR: 0.18; 95% CI 0.05-0.99; p = 0.007].

CONCLUSIONS: This study showed that proactive infliximab monitoring following reactive testing was associated with greater drug persistence and fewer IBD-related hospitalizations than reactive testing alone.

BACKGROUND: The Department of Veterans Affairs (VA) has implemented robust strategies to monitor prescription opioid dispensing, but these strategies have not accounted for opioids prescribed by non-VA providers. State-based prescription drug monitoring programs (PDMPs) are a potential tool to identify VA patients' receipt of opioids from non-VA prescribers, and recent legislation requires their use within VA.

OBJECTIVE: To evaluate VA physicians' perspectives and experiences regarding use of PDMPs to monitor Veterans' receipt of opioids from non-VA prescribers.

DESIGN: Qualitative study using semi-structured interviews.

PARTICIPANTS: Forty-two VA primary care physicians who prescribed opioids to 15 or more Veterans in 2015. We sampled physicians from two states with PDMPs (Massachusetts and Illinois) and one without prescriber access to a PDMP at the time of the interviews (Pennsylvania).

APPROACH: From February to August 2016, we conducted semi-structured telephone interviews that addressed the following topics regarding PDMPs: overall experiences, barriers to optimal use, and facilitators to improve use.

KEY RESULTS: VA physicians broadly supported use of PDMPs or desired access to one, while exhibiting varying patterns of PDMP use dictated by state laws and their clinical judgment. Physicians noted administrative burdens and incomplete or unavailable prescribing data as key barriers to PDMP use. To facilitate use, physicians endorsed (1) linking PDMPs with the VA electronic health record, (2) using templated notes to document PDMP use, and (3) delegating routine PDMP queries to ancillary staff.

CONCLUSIONS: Despite the time and administrative burdens associated with their use, VA physicians in our study broadly supported PDMPs. The application of our findings to ongoing PDMP implementation efforts may strengthen PDMP use both within and outside VA and improve the safe prescribing of opioids.

PURPOSE: Results of a study to estimate the prevalence of look-alike/sound-alike (LASA) medication errors through analysis of Veterans Affairs (VA) administrative data are reported.

METHODS: Veterans with at least 2 filled prescriptions for 1 medication in 20 LASA drug pairs during the period April 2014-March 2015 and no history of use of both medications in the preceding 6 months were identified. First occurrences of potential LASA errors were identified by analyzing dispensing patterns and documented diagnoses. For 7 LASA drug pairs, potential errors were evaluated via chart review to determine if an actual error occurred.

RESULTS: Among LASA drug pairs with overlapping indications, the pairs associated with the highest potential-error rates, by percentage of treated patients, were tamsulosin and terazosin (3.05%), glipizide and glyburide (2.91%), extended- and sustained-release formulations of bupropion (1.53%), and metoprolol tartrate and metoprolol succinate (1.48%). Among pairs with distinct indications, the pairs associated with the highest potential-error rates were tramadol and trazodone (2.20%) and bupropion and buspirone (1.31%). For LASA drug pairs found to be associated with actual errors, the estimated error rates were as follows: lamivudine and lamotrigine, 0.003% (95% confidence interval [CI], 0-0.01%); carbamazepine and oxcarbazepine, 0.03% (95% CI, 0-0.09%); and morphine and hydromorphone, 0.02% (95% CI, 0-0.05%).

CONCLUSION: Through the use of administrative databases, potential LASA errors that could be reviewed for an actual error via chart review were identified. While a high rate of potential LASA errors was detected, the number of actual errors identified was low.