Determinants of Palliative Care Utilization Among Patients Hospitalized With Metastatic Gastrointestinal Malignancies.

BACKGROUND: Gastrointestinal tract cancers account for a significant proportion of the national cancer burden. AIM: We sought to explore patient- and hospital-level determinants of palliative care utilization among patients hospitalized with metastatic gastrointestinal tract cancers using a national database. METHODS: An analysis of the 2012 National Inpatient Sample was performed. International Classification of Diseases, Ninth Revision codes were used to identify hospital discharges associated with metastatic digestive tract cancers and patient/hospital covariates for inclusion in a logistic regression model. Total charges and length of stay were analyzed in a linear regression model. RESULTS: Compared to males, females were more likely to receive inpatient palliative care (adjusted odds ratio [OR] 1.12, P = .002). No difference was seen between white and Asian patients (adjusted OR 1.2, P = .11) or Native Americans patients (adjusted OR 1.4, P = .22). However, relative to white patients, African Americans (adjusted OR 1.13, P = .02) and Hispanics (adjusted OR 1.25, P = .001) had significantly higher odds of inpatient palliative care. Medicare patients were least likely to receive palliative care compared to those with Medicaid or commercial payers. Length of stay during these hospitalizations was longer in African Americans ( P = .0001), Asians ( P = .0001), and Native Americans ( P = .03) compared to white patients. No difference was seen when total charges were compared between white and African American patients ( P = .08). Conversely, total charges were higher in Hispanics ( P = .005) and Asians ( P = .001) relative to white patients. CONCLUSION: Gender and racial differences exist in utilization of inpatient palliative care among patients hospitalized with metastatic gastrointestinal tract cancers.

African Americans Have Better Outcomes for Five Common Gastrointestinal Diagnoses in Hospitals With More Racially Diverse Patients.

OBJECTIVES: We sought to characterize the relationship between hospital inpatient racial diversity and outcomes for African-American patients including rates of major complications or mortality during hospitalization for five common gastrointestinal diagnoses. METHODS: Using the 2012 National Inpatient Sample database, hospital inpatient racial diversity was defined as the percentage of African-American patients discharged from each hospital. Logistic regression was used to predict major complication rates or death, long length of stay, and high total charges. Control variables included age, gender, payer type, patient location, area-associated income quartile, hospital characteristics including size, urban vs. rural, teaching vs. nonteaching, region, and the interaction of the percentage of African Americans with patient race. RESULTS: There were 848,395 discharges across 3,392 hospitals. The patient population was on average 27% minority (s.d.±21%) with African Americans accounting for 14% of all patients. Overall, African-American patients had higher rates of major complications or death relative to white patients (adjusted odds ratio (aOR) 1.19; 95% confidence interval (CI) 1.16-1.23). However, when treated in hospitals with higher patient racial diversity, African-American patients experienced significantly lower rates of major complications or mortality (aOR 0.80; 95% CI 0.74-0.86). CONCLUSIONS: African Americans have better outcomes for five common gastrointestinal diagnoses when treated in hospitals with higher inpatient racial diversity. This has major ramifications on total hospital charges.

Socioeconomic Inequalities in the Utilization of Colorectal Stents for the Treatment of Malignant Bowel Obstruction.

BACKGROUND: Colorectal stents are increasingly employed as a bridge to surgery or for palliative relief of malignant large bowel obstruction. AIM: To explore determinants of inpatient colorectal stent utilization (CRSU). METHODS: An analysis of the 2012 National Inpatient Sample was performed. International Classification of Diseases, 9th revision, codes were used to identify discharges associated with CRSU and patient/hospital factors for inclusion in a logistic regression model. RESULTS: We identified 217,055 inpatient colonoscopies, approximating 1.1 million inpatient colonoscopies nationwide. Colorectal stents were placed in 1.4 % of all procedures. Across all racial groups, Medicare was the most common payer. Patients with commercial insurance had lower CRSU compared with Medicare patients [adjusted odds ratio (OR) 0.83, 95 % confidence interval (CI) 0.75-0.92]. No gender disparities were identified (OR 0.96, 95 % CI 0.89-1.03). In addition, no racial differences in CRSU existed between Caucasians versus African-Americans (OR 0.94, 95 % CI 0.83-1.06) and Caucasians versus Hispanics (OR 0.96, 95 % CI 0.83-1.1). Compared with patients living in less affluent neighborhoods, those residing in more affluent areas had higher CRSU (OR 1.65, 95 % CI 1.46-1.86). This displayed a linear relationship with the odds of CRSU increasing as household income increased. Less affluent patients also had the highest total charges and longest wait time to CRSU. CRSU was highest among patients treated in larger medical centers (OR 1.7, 95 % CI 1.51-1.93) and teaching hospitals (OR 3.9, 95 % CI 3.2-4.8). CONCLUSION: Individuals from less affluent neighborhoods have lower colorectal stent utilization. This disparity is independent of race and likely related to poorer access to healthcare resources.

Assessing the likelihood of new-onset inflammatory bowel disease following tumor necrosis factor-alpha inhibitor therapy for rheumatoid arthritis and juvenile rheumatoid arthritis.

The association between inhibition of tumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and the onset of inflammatory bowel disease (IBD) is unclear. We sought to evaluate this association by analyzing adverse events (AEs) reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) with a standardized scoring tool for drug-induced AEs. A search of the FAERS for RA or JRA (January 2003-December 2011) reported with adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab was performed. This dataset was then queried for cases indicating IBD. Full-length reports were accessed using the Freedom of Information Act and organized by age, sex, concomitant medications, co-morbidities, type of TNF-α inhibitor used, and diagnosis/treatment details. The Naranjo score was used to determine whether the drug-induced AEs were definite, probable, possible, or doubtful. There were 158 cases of IBD after TNF-α inhibitor exposure in RA or JRA patients. Use of the Naranjo score revealed that, in a majority of the cases (71.5 %), TNF-α inhibitor exposure was considered a 'possible' cause. A majority of the 'probable cases' in JRA were reported with etanercept (40 patients, 90.91 %). There were no 'definite' cases of anti-TNF-induced IBD. After applying the Naranjo scale, a weak association between new-onset IBD and TNF-α inhibitor therapy in RA patients and a moderately strong association especially with etanercept exposure in JRA patients was observed. However, causality cannot be determined due to limitations of the FAERS and the Naranjo score.

Melanoma and non-melanoma skin cancer in inflammatory bowel disease patients following tumor necrosis factor-α inhibitor monotherapy and in combination with thiopurines: analysis of the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND AND AIMS: Reports have shown an increased risk of melanoma skin cancer (MSC) with exposure to tumor necrosis factor alpha (TNF-α) inhibitors and non-melanoma skin cancer (NMSC) with thiopurine exposure in inflammatory bowel disease (IBD) patients. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) we sought to evaluate the odds of developing MSC and NMSC for patients on TNF-α inhibitors as monotherapy and in combination therapy with thiopurines and/or steroids. METHODS: The FAERS was queried for reports between January 2003 and June 2012. A proportional reporting ratio (PRR) metric analyses was performed on the data to determine the odds of developing MSC and NMSC. RESULTS: The PRR analysis showed increased odds of developing MSC and NMSC for patients on a TNF-α inhibitor (p-value = 0.035 and p-value = 0.03, respectively) and those on a TNF-α inhibitor in combination with a thiopurine (p-value < 0.001 and p-value < 0.001). CONCLUSION: TNF-α inhibitor monotherapy or use with concomitant thiopurines in patients with IBD is associated with higher odds of developing MSC and NMSC.

Effect of tumor necrosis factor-α inhibitors on drug-induced pancreatitis in inflammatory bowel disease.

BACKGROUND: Mesalamine and thiopurines (6-mercaptopurine and azathioprine) have been shown to increase the risk of developing acute pancreatitis in inflammatory bowel disease (IBD) patients. Tumor necrosis factor-α (TNF-α) inhibitors have been shown to protect against pancreatitis in animal models. OBJECTIVE: To determine the risk of pancreatitis when comparing thiopurine monotherapy, mesalamine monotherapy, and thiopurine and mesalamine dual therapy to identical treatments but with the addition of a TNF-α inhibitor. METHODS: Using a case-control design, the Food and Drug Administration Adverse Event Reporting System was queried for cases of pancreatitis and control reactions in IBD patients on a thiopurine or mesalamine. The proportional reporting ratio method was used to compare the different therapy regimens with the same regimen combined with a TNF-α inhibitor. RESULTS: In all, 549 cases and controls were identified. When comparing thiopurine monotherapy with thiopurines combined with a TNF-α inhibitor, the odds of pancreatitis were lower in those on combination therapy (odds ratio [OR] = 0.04; 95% CI = 0.01-0.12). A similar trend was seen when comparing mesalamine monotherapy to mesalamine combined with a TNF-α inhibitor (OR = 0.08; 95% CI = 0.04-0.14) and when comparing those on both a thiopurine and mesalamine with those on all 3 therapies (OR = 0.04; 95% CI = 0.01-0.16). CONCLUSIONS: Combination therapy with TNF-α inhibitors appears to be associated with a lower risk of pancreatitis in IBD patients on mesalamine, thiopurines, or a combination of both. Physicians should consider using TNF-α inhibitors in those with the greatest risk of pancreatitis, although prospective studies are needed.

Infectious complications of TNF-α inhibitor monotherapy versus combination therapy with immunomodulators in inflammatory bowel disease: analysis of the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND & AIM: Incremental increase in the risk of serious infections with combinations of tumor necrosis factor-alpha (TNF-α) inhibitors and immunomodulators compared to monotherapy with these agents in inflammatory bowel disease (IBD) is unclear. Our aim was to analyze whether there is such an incremental increase in the odds of serious infections. METHODS: The FDA Adverse Event Reporting System (2003 - June 2011) was queried for 'Primary Suspect' reports of various infections with TNF-α inhibitors, systemic corticosteroids and immunomodulators with usage indication of IBD. Odds ratios (ORs) were calculated for baseline odds of infections as well as serious infections (requiring hospitalization and/or death) with monotherapy and combination therapy (compared to 5-Aminosalicylates) as well as incremental increase in odds for dual or triple combination therapy (compared to monotherapy or dual combination therapy respectively) using Fisher's exact test with SPSS 20 (IBM Co. Armonk, NY, USA). RESULTS: TNF-α inhibitor (OR 1.95; CI, 1.06-3.59) and immunomodulator (OR 9.99; CI, 1.28-78.16) monotherapy as well as in combination augmented baseline odds of serious infection for IBD patients. No incremental increase in the odds with combination therapy was seen when an immunomodulator was added to a TNF-α inhibitor (OR 0.37; CI, 0.05-2.80) and when both were used with a systemic corticosteroid (OR 0.91; CI, 0.50-1.66). Variations in these were seen for the individual infection subtypes. CONCLUSIONS: TNF-α inhibitor and immunomodulator monotherapy increase the baseline odds of acquiring a serious infection. Combination therapy with these drugs does not further increase the odds of serious infections compared to monotherapy.

Hospitalizations for vaccine preventable pneumonias in patients with inflammatory bowel disease: a 6-year analysis of the Nationwide Inpatient Sample.

BACKGROUND: Pneumonias are among the most common causes of hospitalization among inflammatory bowel disease (IBD) patients. Guidelines published in 2004 advocate vaccination against Streptococcus pneumoniae and influenza virus. We sought to examine trends in hospitalizations for vaccine preventable pneumonias among IBD patients since the availability of published guidelines, and to identify whether Haemophilus influenzae is a causative organism for pneumonia hospitalizations among IBD patients. METHODS: This cross-sectional study on the Nationwide Inpatient Sample was used to identify admissions for pneumonias in patients with IBD between 2004 and 2009. A multivariate logistic regression analysis was performed comparing IBD patients to controls, accounting for potential confounders. RESULTS: There were more admissions for S. pneumoniae pneumonia than influenza virus or H. influenzae (787, 393, and 183 respectively). Crohn's disease (CD) as well as ulcerative colitis (UC) patients did not demonstrate increased adjusted odds of hospitalization for S. pneumoniae pneumonia (1.08; confidence interval [CI] 0.99-1.17 compared to 0.93; CI 0.82-1.06 respectively). Increased adjusted odds for hospitalization for pneumonias due to influenza virus were seen among UC patients in the bottom quartile of income (1.86; CI 1.46-2.37). Adjusted odds for H. influenzae pneumonia admission in patients with UC and CD patients were increased compared to controls (1.42; CI 1.13-1.79 and 1.28; CI 1.06-1.54, respectively). CONCLUSION: The study identified lowest income UC patients as having higher adjusted odds, and these patients should be targeted for influenza virus vaccination. Additionally, H. influenzae may be another vaccine preventable cause for pneumonia among IBD patients.

Alleged isotretinoin-associated inflammatory bowel disease: disproportionate reporting by attorneys to the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Some studies have purported to link isotretinoin prescribed for acne with the development of inflammatory bowel disease (IBD). OBJECTIVE: We sought to identify existence of disproportionate attorney-initiated reporting of isotretinoin-associated IBD in the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: A total of 3,338,835 cases (2003-2011) were downloaded from the FAERS. These were queried for IBD cases reported with isotretinoin for a usage indication of acne while recording reporter category. Trends were analyzed over time for reports by attorneys for all medications compared with reports of IBD with isotretinoin. Signal inflation factor was calculated to determine the distortion of pharmacovigilance signals for IBD with isotretinoin. RESULTS: There were 2214 cases of IBD resulting from isotretinoin. Attorneys reported 1944 (87.8%) cases whereas physicians reported 132 (6.0%) and consumers reported 112 (5.1%) cases (P value < .01). For the entire FAERS, only 87,905 of the total 2,451,314 (3.6%) reports for all drug reactions during the same time period were reported by attorneys (P value < .01). The signal inflation factor for IBD with isotretinoin for attorney-initiated reports was 5.82, signifying a clear distortion. LIMITATIONS: The accuracy of reports was not ascertained. CONCLUSIONS: Attorney-initiated reports inflate the pharmacovigilance signal of isotretinoin-associated IBD in the FAERS.

Ischaemic colitis in rheumatoid arthritis patients receiving tumour necrosis factor-α inhibitors: an analysis of reports to the US FDA Adverse Event Reporting System.

BACKGROUND: Tumour necrosis factor-α (TNF-α) inhibitors are immunosuppressants, approved for the treatment and maintenance of rheumatoid arthritis (RA). Immunosuppression has been shown to induce ischaemic colitis (IC) in an animal model; however, a relationship between TNF inhibitors and IC has rarely been reported in the published literature. OBJECTIVE: The aim of this study was to better characterize the association between TNF-α inhibitors with IC in RA patients, by analysing adverse event reports submitted to the US FDA Adverse Event Reporting System (AERS) and the published literature. METHODS: The FDA AERS database was searched and we identified all reports between January 2003 and June 2011. The search was limited to an indication of RA, a 'primary suspect' drug of TNF-α inhibitors and a reaction of IC. Full-length reports were obtained and analysed utilizing the Freedom of Information Act. The cases were organized by age, sex, type of TNF-α inhibitor, concomitant drugs and medical co-morbidities. Cases were labelled as definite, probable, possible or doubtful drug-induced adverse events based on the Naranjo Scale. A PubMed search was performed to obtain published literature documenting events of anti-TNF-associated IC. RESULTS: Twelve cases were eliminated because of more likely causes for IC. Thirty-five primary suspect reports of TNF-α inhibitors associated with IC in RA patients were identified in the FDA AERS. Thirteen cases were reported with infliximab, 12 with adalimumab, 7 with etanercept and 3 with certolizumab. The majority of the cases were in females (29/35) and those between the ages of 50 and 65 years (18/35). Use of the Naranjo Scale revealed 17 probable and 18 possible cases of anti-TNF-induced IC. In the literature, one report of IC associated with adalimumab was identified. CONCLUSION: TNF-α inhibitors may be initiating factors or co-factors in the development of IC in RA patients, and further research to determine the mechanism of this association is warranted.

Ischemic colitis with type I interferons used in the treatment of hepatitis C and multiple sclerosis: an evaluation from the food and drug administration adverse event reporting system and review of the literature.

OBJECTIVE: To better characterize the association between type I interferons and ischemic colitis (IC) in patients with the hepatitis C virus (HCV) and multiple sclerosis (MS), by analyzing reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) and the published literature. DATA SOURCES: A total of 2,562,390 reports of adverse events between January 2003 and June 2011 were downloaded from the FDA AERS. A literature review was performed on PubMed (January 1966-August 2012) using the MeSH terms interferon or interferon alfa or interferon beta and ischemic colitis separated by the Boolean operator "and" between the first 3 terms and the last term. Additional literature was identified by conducting a hand search of the reference list of the published literature identified in the initial search. STUDY SELECTION AND DATA EXTRACTION: Cases were restricted to those with an indication of HCV or MS, a primary suspect drug of a type I interferon, and a reaction of IC. Full-length reports were requested and organized by type of interferon, age, sex, concomitant drugs, and comorbidities. The Naranjo probability scale was used to define cases as definite, probable, possible, or doubtful drug-induced adverse events. DATA SYNTHESIS: Type I interferons, including interferon alfa (IFN-α) and interferon beta (IFN-ß), are approved for the treatment of HCV and MS. IFN-α has been shown to induce IC, but a relationship between type I interferons and IC has not been clarified in the medical literature. Fifty-six primary suspect reports of type I interferons associated with IC in patients with HCV or MS were identified from the FDA AERS. Seventeen cases were reported with IFN-α and 39 cases were reported with IFN-ß. The majority of the cases were in females (80%) and those between the ages of 50 and 65 years (52%). The Naranjo probability scale identified 13 probable and 4 possible cases of IFN-α-induced IC, and 19 probable and 20 possible cases of IFN-ß-induced IC. In the literature, 11 cases of IFN-α-induced IC were reported, while there were no reports with IFN-ß. CONCLUSIONS: Our study suggests a possible association between treatment with type I interferons and the development of IC. Further research to determine the mechanism of this association is warranted.

Simulated comparison of topical and oral formulations of 5-aminosalicylate for the treatment of ulcerative colitis.

BACKGROUND: 5-Aminosalicylate (5-ASA) formulations are approved for the treatment of ulcerative colitis (UC). Determination of the colonic pharmacokinetics of 5-ASA is challenging. A dynamic model of 5-ASA colonic amounts after oral delayed-release 5-ASA (Asacol), oral extended delayed-release 5-ASA (Lialda), 5-ASA enema (Rowasa), foam and suppositories (Canasa) was developed to determine the colonic kinetics of these agents. METHODS: We created a model with Stella software. Colonic 5-ASA in the right, transverse, descending, sigmoid colon, and rectum were estimated for adults after recommended doses of the above formulations. Simulations of active mild/moderate UC and in remission were performed and compared using Student's t-test for differences in means. RESULTS: For UC in remission, the highest amounts of 5-ASA were from Asacol in the right and transverse colon (P < 0.01), Lialda in the descending and sigmoid colon (P < 0.01), and Rowasa in the rectum (P < 0.01). For active UC, sigmoid amounts were highest with foam (P < 0.01), and rectal amounts highest with Rowasa (P < 0.01). Differences in rectosigmoid amounts of 5-ASA from enemas and suppositories for UC in remission occurred based on the relationship between the timing of administration relative to the daily bowel movement (P < 0.01). CONCLUSIONS: Compared to Asacol, Lialda results in higher 5-ASA amounts in the left colon. Asacol with Rowasa provides highest 5-ASA amounts across the entire colon. Higher 5-ASA amounts from topical formulations occur when the insertion occurs soon after the daily bowel movement. This model provides a rationale for further investigation.

Wheel running can accelerate or delay extinction of conditioned place preference for cocaine in male C57BL/6J mice, depending on timing of wheel access.

Aerobic exercise may represent a useful intervention for drug abuse in predisposed individuals. Exercise increases plasticity in the brain that could be used to reverse learned drug associations. Previous studies have reported that exposing mice to a complex environment including running wheels after drug conditioning abolishes conditioned place preference (CPP) for cocaine, whereas running can enhance CPP when administered before conditioning. The purpose of the present study was to test the hypothesis that timing of exercise relative to conditioning has opposing effects on cocaine CPP. Male C57BL/6J mice experienced 30 days of running or sedentary treatments either before or after cocaine conditioning. Control animals always received saline and never cocaine, but otherwise underwent the same conditioning and exercise treatments. Animals were given bromodeoxyuridine injections at the onset of conditioning or exercise, and euthanized at the end of the study to quantify survival of new neurons in the hippocampus as a marker of plasticity. Wheel running accelerated extinction of CPP when running occurred entirely after drug conditioning, whereas running delayed extinction when administered before conditioning. A single conditioning day after running was sufficient to abolish the accelerated extinction observed when all conditioning preceded running. Running approximately doubled adult hippocampal neurogenesis, whereas cocaine had no effect. These results suggest that exercise-induced plasticity can facilitate learning that context is no longer associated with drug. However, if drug exposure occurs after exercise, running-induced plasticity may strengthen drug associations. The results provide insights into the interaction between exercise and drug conditioning that could have implications for drug abuse treatments.