Andrew L. Masica M.D.

Girard, T. D., M. C. Exline, S. S. Carson, C. L. Hough, P. Rock, M. N. Gong, I. S. Douglas, A. Malhotra, R. L. Owens, D. J. Feinstein, B. Khan, M. A. Pisani, R. C. Hyzy, G. A. Schmidt, W. D. Schweickert, R. D. Hite, D. L. Bowton, A. L. Masica, J. L. Thompson, R. Chandrasekhar, B. T. Pun, C. Strength, L. M. Boehm, J. C. Jackson, P. P. Pandharipande, N. E. Brummel, C. G. Hughes, M. B. Patel, J. L. Stollings, G. R. Bernard, R. S. Dittus and E. W. Ely (2018). “Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness.” N Engl J Med Oct 22. [Epub ahead of print].

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BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522.)

Asrani, S. K., M. Kouznetsova, G. Ogola, T. Taylor, A. Masica, B. Pope, J. Trotter, P. Kamath and F. Kanwal (2018). “Increasing Health Care Burden of Chronic Liver Disease Compared With Other Chronic Diseases, 2004-2013.” Gastroenterology 155(3): 719-729.e714.

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BACKGROUND & AIMS: Chronic liver disease (CLD) is a common and expensive condition, and studies of CLD-related hospitalizations have underestimated the true burden of disease. We analyzed data from a large, diverse health care system to compare time trends in CLD-related hospitalizations with those in congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD). METHODS: We collected data from a large health care system in Texas on hospitalizations related to CLD (n = 27,783), CHF (n = 60,415), and COPD (n = 34,199) from January 1, 2004 through December 31, 2013. We calculated annual hospitalization rates (per 100,000) and compared hospital course, inpatient mortality, ancillary services, and readmissions. RESULTS: Compared with patients with CHF (median age, 71 years) or COPD (median age, 69 years), patients with CLD were significantly younger (median age, 57 years) (P < .01 vs CHF and COPD). Higher proportions of patients with CLD were uninsured (11.7% vs 5.4% for CHF and 5.4% for COPD, P < .01) and Hispanic (17% for CLD vs 9.3% for CHF and 5.0% for COPD, P < .01). A lower proportion of patients with CLD had Medicare (41.5% vs 68.6% with CHF and 70.1% with COPD, P < .01). From 2004 through 2013, the rate of CLD-related hospitalization increased by 92% (from 1295/100,000 to 2490/100,000), compared with 6.7% for CHF (from 3843/100,000 to 4103/100,000) and 48.8% for COPD (from 1775/100,000 to 2642/100,000). During this time period, CLD-related hospitalizations covered by Medicare increased from 31.8% to 41.5%, whereas hospitalizations covered by Medicare did not change for CHF (remained at 70%) or COPD (remained at 70%). Patients with CLD had longer hospital stays (7.3 days vs 6.2 days for CHF and 5.9 days for COPD, P < .01). A higher proportion of patients with CLD died or were discharged to hospice (14.2% vs 11.5% of patients with CHF and 9.3% of patients with COPD, P < .01), and a smaller proportion had access to postacute care (13.2% vs 23.2% of patients with CHF and 27.4% of patients with COPD, P < .01). A higher proportion of patients with CLD were readmitted to the hospital within 30 days (25% vs 21.9% of patients with CHF and 20.6% with COPD, P < .01). CONCLUSIONS: Patients with CLD, compared with selected other chronic diseases, had increasing rates of hospitalization, longer hospital stays, more readmissions, and, despite these adverse outcomes, less access to postacute care. Disease management models for CLD are greatly needed to manage the anticipated increase in hospitalizations for CLD.

Asrani, S. K., M. Kouznetsova, G. Ogola, T. Taylor, A. Masica, B. Pope, J. Trotter, P. Kamath and F. Kanwal (2018). “Increasing Healthcare Burden of Chronic Liver Disease Compared to Other Chronic Diseases, 2004-2013.” Gastroenterology. May 23. [Epub ahead of print].

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BACKGROUND & AIMS: Chronic liver disease (CLD) is a common and expensive condition, and studies of CLD-related hospitalizations have underestimated the true burden of disease. We analyzed data from a large diverse healthcare system to compare time trends in CLD-related hospitalizations with those of congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD). METHODS: We collected data from a large healthcare system in Texas on hospitalizations related to CLD (n=27,783), CHF (n=60,415), and COPD (n=34,199) from January 1, 2004 through December 31, 2013. We calculated annual hospitalization rates (per 100,000) and compared hospital course, inpatient mortality, ancillary services and re-admissions. RESULTS: Compared to patients with CHF (median age, 71 years) or COPD (median age 69 years), patients with CLD were significantly younger (median age 57 years; P<.01 vs CHF and COPD). Higher proportions of patients with CLD were uninsured (11.7% vs 5.4% for CHF and 5.4% for COPD; P<.01) and Hispanic (17% for CLD vs 9.3% for CHF and 5.0% for COPD; P<.01). A lower proportion of patients with CLD had Medicare (41.5% vs 68.6% with CHF and 70.1% with COPD; P<0.01). From 2004 through 2013, the rate of CLD-related hospitalization increased by 92% (from 1295/100,000 to 2490/100,000), compared to 6.7% for CHF (from 3843/100,000 to 4103/100,000) and 48.8% for COPD (from 1775/100,000 to 2642/100,000). During this time period, CLD-related hospitalizations covered by Medicare increased from 31.8% to 41.5%, whereas hospitalizations covered by Medicare did not change for CHF (remained at 70%) or COPD (remained at 70%). Patients with CLD had longer hospital stays (7.3 days vs 6.2 days for CHF or 5.9 days for COPD; P<.01). A higher proportion of patients with CLD died or were discharged to hospice (14.2% vs 11.5% of patients with CHF and 9.3% of patients with COPD P<.01), and a smaller proportion had access to post-acute care (13.2% vs 23.2% of patients with CHF and 27.4% of patients with COPD; P<.01). A higher proportion of patients with CLD were readmitted to the hospital within 30 days (25% vs 21.9% of patients with CHF and 20.6% with COPD; P<.01). CONCLUSIONS: Patients with chronic liver disease, compared to selected other chronic diseases, had increasing rates of hospitalization, longer hospital stays, more readmissions, and, despite these adverse outcomes, less access to post-acute care. Disease management models for chronic liver disease are greatly needed to manage the anticipated increase in hospitalizations for CLD.

Scherrer, J. F., J. Salas, F. D. Schneider, K. K. Bucholz, M. D. Sullivan, L. A. Copeland, B. K. Ahmedani, T. Burroughs and P. J. Lustman (2017). “Characteristics of new depression diagnoses in patients with and without prior chronic opioid use.” J Affect Disord 210: 125-129.

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Chronic use (>90 Days) of opioid analgesics significantly increases the risk of development of new depression episodes (NDE). It is unclear whether depression that develops in this manner is similar to or different from NDE in persons not exposed to opioid analgesic use (OAU). METHODS: VA patients were classified into two groups, those who did not receive an opioid and developed depression (non-OAU+NDE, n=4314) and those that had >90 days OAU and developed NDE (OAU+NDE, n=444). OAU+NDE patients were compared to non-OAU+NDE in terms of depression severity (PHQ-9 scores), incidence of PTSD, other anxiety disorders and substance use disorders after NDE, receipt of acute phase antidepressant treatment, dual antidepressant treatment, mood stabilizers and atypical antipsychotics. Prior to computing bivariate analysis, the prevalence of pain conditions and average maximum pain scores were equalized between the two groups using propensity scores and inverse probability of treatment weighting. RESULTS: Controlling for pain, OAU+NDE patients had more depression symptoms (p=.012), more incident PTSD (p=.04) and opioid abuse/dependence and were more likely to receive 12 weeks of antidepressant treatment (p<.0001). Last, non-OAU+NDE were more likely to have incident diagnoses for any other anxiety disorder (p=.014). CONCLUSIONS: Within the limitations of electronic medical record data, results indicate OAU+NDE patients have more depression symptoms, greater treatment adherence and different comorbid psychiatric conditions compared to non-OAU+NDE, independent of pain. Overall OAU related depression is as severe as non-OAU related depression and repeated depression screening in chronic opioid therapy may be warranted for pain patients, regardless of pain severity.