Yash Shah

Overall and Comparative Risk of Herpes Zoster With Pharmacotherapy for Inflammatory Bowel Diseases: A Nationwide Cohort Study.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) might be at increased risk for herpes zoster infection. We sought to quantify the risk of herpes zoster in patients with IBD and evaluate the effects of IBD and IBD medications on the risk of herpes zoster. METHODS: We conducted 2 retrospective studies of populations of Veterans, from January 2000 through June 2016. In study 1, we compared the incidence of herpes zoster among patients with IBD receiving 5‐ASA alone vs matched patients without IBD. In study 2, we compared the incidence of herpes zoster among patients with IBD treated with only 5‐ASA, with thiopurines, with antagonists of tumor necrosis factor (TNF), with a combination of thiopurines and TNF antagonists, and with vedolizumab. We used multivariable Cox regression to estimate the hazard ratios and 95% CIs for herpes zoster associated with IBD in study 1 and with different treatments in study 2. We also estimated the incidence rate of herpes zoster based on age and IBD medication subgroups. RESULTS: Compared to no IBD, ulcerative colitis (UC) and Crohns disease (CD) were each associated with significantly increased risk of herpes zoster infection. In multivariable Cox regression (compared to no IBD), UC, CD, or IBD treated with 5‐ASA treatment alone was associated with significantly increased risk of herpes zoster, with adjusted HRs (AHR) of 1.81 for UC (95% CI, 1.56–2.11), 1.56 for CD (95% CI, 1.28–1.91), and 1.72 for treated IBD (95% CI, 1.51–1.96). In multivariable Cox regression analysis, compared to exposure to 5‐ASA alone, exposure to thiopurines (AHR, 1.47; 95% CI, 1.31–1.65) or a combination of thiopurines and TNF antagonists (AHR, 1.65; 95% CI, 1.22–2.23) was associated with increased risk of herpes zoster. However, exposure to TNF antagonists alone (AHR, 1.15; 95% CI, 0.96–1.38) was not associated with increased risk of herpes zoster. The incidence rates of herpes zoster in all age groups and all IBD medication subgroups were substantially higher than that in the oldest group of patients without IBD (older than 60 years). CONCLUSIONS: In 2 retrospective studies of Veteran populations, we associated IBD and treatment with thiopurines, alone or in combination with TNF antagonists, with increased risk of herpes zoster. With the approval of a new and potentially safer vaccine for herpes zoster, the effects of immunization of patients with IBD should be investigated.

Association of Hospital Participation in a Medicare Bundled Payment Program With Volume and Case Mix of Lower Extremity Joint Replacement Episodes

Importance Medicare’s Bundled Payments for Care Improvement (BPCI) initiative for lower extremity joint replacement (LEJR) surgery has been associated with a reduction in episode spending and stable-to-improved quality. However, BPCI may create unintended effects by prompting participating hospitals to increase the overall volume of episodes paid for by Medicare, which could potentially eliminate program-related savings or prompt them to shift case mix to lower-risk patients. Objective To evaluate whether hospital BPCI participation for LEJR was associated with changes in overall volume and case mix. Design, Setting, and Participants Observational study using Medicare claims data and a difference-in-differences method to compare 131 markets (hospital referral regions) with at least 1 BPCI participant hospital (n = 322) and 175 markets with no participating hospitals (n = 1340), accounting for 580 043 Medicare beneficiaries treated before (January 2011-September 2013) and 462 161 after (October 2013-December 2015) establishing the BPCI initiative. Hospital-level case-mix changes were assessed by comparing 265 participating hospitals with a 1:1 propensity-matched set of nonparticipating hospitals from non-BPCI markets. Exposures Hospital BPCI participation. Main Outcomes and Measures Changes in market-level LEJR volume in the before vs after BPCI periods and changes in hospital-level case mix based on demographic, socioeconomic, clinical, and utilization factors. Results Among the 1 717 243 Medicare beneficiaries who underwent LEJR (mean age, 75 years; 64% women; and 95% nonblack race/ethnicity), BPCI participation was not significantly associated with a change in overall market-level volume. The mean quarterly market volume in non-BPCI markets increased 3.8% from 3.8 episodes per 1000 beneficiaries before BPCI to 3.9 episodes per 1000 beneficiaries after BPCI was launched. For BPCI markets, the mean quarterly market volume increased 4.4% from 3.6 episodes per 1000 beneficiaries before BPCI to 3.8 episodes per 1000 beneficiaries after BPCI was launched. The adjusted difference-in-differences estimate between the market types was 0.32% (95% CI, −0.06% to 0.69%; P = .10). Among 20 demographic, socioeconomic, clinical, and utilization factors, BPCI participation was associated with differential changes in hospital-level case mix for only 1 factor, prior skilled nursing facility use (adjusted difference-in-differences estimate, −0.53%; 95% CI, −0.96% to −0.10%; P = .01) in BPCI vs non-BPCI markets. Conclusions and Relevance In this observational study of Medicare beneficiaries who underwent LEJR, hospital participation in Bundled Payments for Care Improvement was not associated with changes in market-level lower extremity joint replacement volume and largely was not associated with changes in hospital case mix. These findings may provide reassurance regarding 2 potential unintended effects associated with bundled payments for LEJR.

Assessing the Optimal Position for Vedolizumab in the Treatment of Ulcerative Colitis: A Simulation Model

Background Vedolizumab, an α4β7 integrin monoclonal antibody inhibiting gut lymphocyte trafficking, is an effective treatment for ulcerative colitis (UC). We evaluated the optimal position of vedolizumab in the UC treatment paradigm. Methods Using Markov modeling, we assessed multiple algorithms for the treatment of UC. The base case was a 35-year-old male with steroid-dependent moderately to severely active UC without previous immunomodulator or biologic use. The model included 4 different algorithms over 1 year, with vedolizumab use prior to: initiating azathioprine (Algorithm 1), combination therapy with infliximab and azathioprine (Algorithm 2), combination therapy with an alternative anti-tumor necrosis factor (anti-TNF) and azathioprine (Algorithm 3), and colectomy (Algorithm 4). Transition probabilities and quality-adjusted life-year (QALY) estimates were derived from the published literature. Primary analyses included simulating 100 trials of 100,000 individuals, assessing clinical outcomes, and QALYs. Sensitivity analyses employed longer time horizons and ranges for all variables. Results Algorithm 1 (vedolizumab use prior to all other therapies) was the preferred strategy, resulting in 8981 additional individuals in remission, 18 fewer cases of lymphoma, and 1087 fewer serious infections per 100,000 patients compared with last-line use (A4). Algorithm 1 also resulted in 0.0197 to 0.0205 more QALYs compared with other algorithms. This benefit increased with longer time horizons. Algorithm 1 was preferred in all sensitivity analyses. Conclusion The model suggests that treatment algorithms positioning vedolizumab prior to other therapies should be considered for individuals with moderately to severely active steroid-dependent UC. Further prospective research is needed to confirm these simulated results.

Segmental resection is a safe oncologic alternative to total proctocolectomy in elderly patients with ulcerative colitis and malignancy

The standard approach for the surgical management of colorectal cancer (CRC) in the setting of ulcerative colitis (UC) involves total proctocolectomy (TPC). However, some patients also undergo a partial resection (PR). This may be an attractive option in older patients with a high risk for surgery. The aim of this study was to compare the risk of metachronous cancer after PR or TPC for CRC in the setting of UC.

The Natural History of Newly Diagnosed Ulcerative Colitis in Patients with Concomitant Primary Sclerosing Cholangitis

Background and Aims Primary sclerosing cholangitis (PSC) is commonly associated with ulcerative colitis (UC). Our aim was to compare the course of disease in patients with UC-PSC and UC alone in a nationwide cohort. Methods We conducted a retrospective cohort study among nation-wide Veterans Affairs (VA) patients newly diagnosed with UC to determine the association between PSC status and clinical outcomes related to UC disease course. This study was divided into 2 groups of patients: (1) The incident UC-PSC group and (2) the incident UC-alone group. Follow-up began at the time of index colonoscopy that diagnosed UC and ended at the first occurrence of the respective outcome for the regression analysis of the following censoring events: (1) colectomy, (2) death, (3) end of follow-up, and (4 lost to follow-up. Results The analysis included 836 UC patients without PSC and 74 UC-PSC patients. In univariate comparisons, PSC patients were more likely to have more extensive UC than those without PSC. In a multivariable Cox regression analysis adjusting for sex, age at UC diagnosis, race, severity of UC, and extent of UC, PSC status was not associated with the risk of colectomy for UC, increased risk of receiving ≥ 2 courses of steroids for UC, or with the risk of receiving immunomodulators for UC. Conclusion UC-PSC patients do not have a more benign disease course than UC patients without PSC. UC-PSC patients may have a modestly increased risk for multiple courses of steroids, which may be mediated by more extensive colonic involvement.

The Severity of Herpes Zoster in Inflammatory Bowel Disease Patients Treated With Anti-TNF Agents

Aim There is a paucity of data on the clinical course and the factors affecting the clinical course of herpes zoster (HZ) in inflammatory bowel disease (IBD). Our aim was to determine the impact of anti-TNF therapy and other factors on the clinical course of HZ in IBD patients. Methods We conducted a retrospective cohort study among a cohort of nation-wide Veterans Affairs patients with IBD who developed incident HZ. The exposed group consisted of eligible study patients who were actively exposed to anti-TNF alone or anti-TNF plus thiopurines at the time of HZ onset. The unexposed group consisted of patients who were only exposed to 5-ASA agents before the onset of HZ without any exposure to anti-TNF medications. The outcome of interest was the development of severe HZ that was defined by including various HZ complications. Results A total of 295 patients were identified with an incident HZ flare during follow- up duration, and among them 69 met the definition of having a severe flare. In multivariable logistic regression analysis adjusting for sex, age at HZ flare onset, race, Charlson comorbidity score, and receipt of oral anti-HZ treatment, exposure to anti-TNF agent was not associated with an increased risk of severe HZ flare compared to exposure to mesalamine alone (adjusted relative risk (RR) 1.1, 95% confidence intervals (CI): 0.75-1.55). Among the covariates, receipt of oral anti-HZ treatment (adjusted RR 0.42, 95% CI: 0.29-0.61), advancing age at HZ onset (adjusted RR for each year increase in age 1.02, 95% CI: 1.00-1.04), and African-American race (adjusted RR with whites as reference 1.58, 95% CI: 1.02-2.44) were significantly associated with the risk of having severe HZ flare. Conclusion Our study showed that among IBD patients who developed HZ, treatment with anti-TNF agents was not associated with increased risk of developing severe HZ as compared to patients treated with 5-ASA therapy only. 10.1093/ibd/izx115_video1izx115_Video_15786486963001.

Comparison Of Hospitals Participating In Medicare’s Voluntary And Mandatory Orthopedic Bundle Programs

We analyzed data from Medicare and the American Hospital Association Annual Survey to compare characteristics and baseline performance among hospitals in Medicares voluntary (Bundled Payments for Care Improvement initiative, or BPCI) and mandatory (Comprehensive Care for Joint Replacement Model, or CJR) joint replacement bundled payment programs. BPCI hospitals had higher mean patient volume and were larger and more teaching intensive than were CJR hospitals, but the two groups had similar risk exposure and baseline episode quality and cost. BPCI hospitals also had higher cost attributable to institutional postacute care, largely driven by inpatient rehabilitation facility cost. These findings suggest that while both voluntary and mandatory approaches can play a role in engaging hospitals in bundled payment, mandatory programs can produce more robust, generalizable evidence. Either mandatory or additional targeted voluntary programs may be required to engage more hospitals in bundled payment programs.

Albumin as a prognostic marker for ulcerative colitis

AIM To evaluate the role of albumin at the time of ulcerative colitis (UC) diagnosis in predicting the clinical course of disease. METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia (i.e., ≤ 3.5 gm/dL) or normal albumin levels (i.e., > 3.5 gm/dL) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined as albumin level ≤ 3.5 g/dL at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids (CS), thiopurines, anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients, but 92 (11.4%) patients did not have their albumin levels checked at the time of UC diagnosis, and they were excluded. A total of 710 patients, who had albumin levels checked at time of UC diagnosis, were included in our study. Amongst them, 536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use (adjusted HR = 1.7, 95%CI: 1.3-2.3), higher likelihood of thiopurine or anti- TNF use (adjusted HR = 1.72, 95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients, but it was not statistically significant (Adjusted HR = 1.7, 95%CI: 0.90-3.25). CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis.