Predictors, rates, and trends of opioid use disorder among patients hospitalized with chronic pancreatitis.

BACKGROUND: Patients with chronic pancreatitis (CP) suffer from pain and receive increased opioid prescriptions with a high risk of opioid use disorder (OUD). We studied the predictors, trends and outcomes of OUD among patients hospitalized with CP. METHODS: Records with CP (with/without OUD) were extracted from the Nationwide Inpatient Sample (NIS) 2012-2014, and the association of OUD with the burden of CP was calculated. We then charted the trends of OUD and its interaction with concomitant CP from NIS 2007-2014 (SAS 9.4). RESULTS: In the period 2012-2014, 4349 (4.99%) of the 87,068 CP patients had concomitant OUD, with higher risk among patients who were young, females, white vs. Hispanics, and individuals with chronic back pain, arthritis, non-opioid substance use, mental health disorders, and those hospitalized in urban centers. OUD was associated with a longer hospital stay (6.9 vs. 6.5 days, P=0.0015) but no significant difference in charges ($47,151 vs. $49,017, P=0.0598) or mortality (1.64% vs. 0.74%, P=0.0506). From 2007-2014, the average yearly rate of OUD was 174 cases per 10,000 hospitalizations (174/10,000), almost 3 times higher among CP vs. non-CP (479/10,000 vs. 173/10,000, P<0.001), and it increased from 2007 to 2014 (135/10,000 to 216/10,000, P<0.001). The yearly increase was 2.7 times higher among patients with CP vs. non-CP (29.9/10,000 vs. 11.3/10,000 hospitalizations/year, P<0.001). CONCLUSIONS: CP is associated with higher rates and trends of OUD. Patients with CP at high risk of OUD may benefit from alternate analgesic regimens or surveillance for OUD when they are prescribed opioids.

Different Hospital Readmissions and Outcomes of Acute Pancreatitis.

OBJECTIVES: Although acute pancreatitis (AP) is associated with recurrent hospitalizations, the impact of different hospital readmissions (DHR) versus same hospital readmissions (SHR) on outcomes is unknown. We study the burden of DHR among readmissions after survival from AP hospitalizations. METHODS: Among adult AP patients (Nationwide Readmissions Database), we calculated the prevalence, trends, and predictors of DHR, and its impact on mortality, hospital stay, and charges during 30- and 90-day readmissions. RESULTS: From 2010 to 2014, 15% and 26% of AP hospitalizations (422,950) were readmitted in 30 and 90 days, respectively. The DHR rates were similar (26.3%, 30 days; 26.4%, 90 days) and unchanged from 2010 to 2014 (Ptrends > 0.10). The predictors of DHR were similar during both readmissions and included younger age category (18-45 years), hospital characteristics (nonteaching, small bed size, nonmicropolitan/metropolitan areas), substance abuse, comorbidities, and nonreception of cholecystectomy and pancreatectomy during index hospitalizations.During readmissions (30 and 90 days), DHR was associated with adjusted odds ratio (95% confidence interval), higher mortality (1.40 [1.19-1.64] and 1.50 [1.32-1.71]), longer hospital stay (1.3 days [1.1-1.7 days] and 1.1 days [0.9-1.3 days]), and higher charges (US $16,779 [US $13,898-US $20,254] and US $14,299 [US $12,299-US $16,623]). CONCLUSIONS: Targeted measures are needed toward patients at risk for DHR to curb the poor outcomes.

Predictors, burden and impact of cardiac arrhythmias among patients hospitalized with end-stage liver disease.

BACKGROUND: Cirrhotic cardiomyopathy, hyperammonemia, and hepatorenal syndrome predispose to cardiac arrhythmias in End-stage liver disease (ESLD). OBJECTIVES: Among ESLD hospitalizations, we evaluate the distribution and predictors of arrhythmias and their impact on hospitalization outcomes. METHODS: We selected ESLD records from the Nationwide Inpatient Sample (2007-2014), identified concomitant arrhythmias (tachyarrhythmias and bradyarrhythmias), and their demographic and comorbid characteristics, and estimated the effect of arrhythmia on outcomes (SAS 9.4). RESULTS: Of 57,119 ESLD hospitalizations, 6,615 had arrhythmias with higher odds with increasing age, males, jaundice, hepatorenal syndrome, alcohol use, and cardiopulmonary disorders. The most common arrhythmias were atrial fibrillation, cardiac arrest/asystole, and ventricular tachycardia. After propensity-matching (arrhythmia: no-arrhythmia, 6,609:6,609), arrhythmias were associated with 200% higher mortality, 1.7-days longer stay, $32,880 higher cost, and higher rates of shock, respiratory and kidney failures. CONCLUSIONS: Due to worse outcomes with arrhythmias, there is a need for better screening and follow-up of ESLD patients for dysrhythmias.

Inferior Outcomes of Patients With Acute Myocardial Infarction and Comorbid Protein-Energy Malnutrition.

BACKGROUND: Protein-energy malnutrition (PEM) diminishes amino acid and energy availability, impairing the body's healing capability after injury, such as in myocardial damage following acute myocardial infarction (AMI). AIMS: We sought to investigate the influence of PEM on clinical outcomes of AMI. METHODS: We identified records with a primary discharge diagnosis of AMI from the Nationwide Inpatient Sample (2012-2014), stratified by concomitant PEM. We matched PEM to no-PEM (1:1) using a greedy algorithm-based propensity methodology and estimated the impact of PEM on health outcomes (SAS 9.4). RESULTS: Of the 332,644 hospitalizations for AMI, 11,675 had concomitant PEM accounting for roughly $US 1.5 billion and over 119,792 hospital days. PEM was associated with older age (74.43- vs. 66.90-years; P < 0.0001), female sex (49.19% vs. 38.44%; P < 0.0001), black race (12.78% vs. 10.46%; P < 0.0001), and higher comorbidity burden (Deyo > 3: 32.77% vs. 16.69%; P < 0.0001). After propensity matching, PEM was associated with higher mortality (Adjusted odds ratio [AOR]: 1.59 [1.46-1.73]), cardiogenic shock (AOR: 2.26 [2.08-2.44]), discharge to secondary facilities (AOR: 2.21 [2.10-2.33]), charges ($135,500 [$131,956-139,139] vs. $81,084 [$79,241-82,970]), cardiac artery bypass surgery (AOR:1.81 [1.66-1.97]), intra-aortic balloon pump placement (AOR: 1.83 [1.65-2.04]) and longer length of stay (10.15- vs. 5.52-days). CONCLUSIONS: PEM is a predisposing factor for devastating clinical outcomes among AMI hospitalizations. Higher prevention, identification and management of PEM among high-risk individuals (older age, female sex, and black race) residing in the community are needed.

Prevalence, trends, outcomes, and disparities in hospitalizations for nonalcoholic fatty liver disease in the United States.

BACKGROUND: As the frequency of nonalcoholic fatty liver disease (NAFLD) continues to rise in the United States (US) community, more patients are hospitalized with NAFLD. However, data on the prevalence and outcomes of hospitalizations with NAFLD are lacking. We investigated the prevalence, trends and outcomes of NAFLD hospitalizations in the US. METHODS: Hospitalizations with NAFLD were identified in the National Inpatient Sample (2007-2014) by their ICD-9-CM codes, and the prevalence and trends over an 8-year period were calculated among different demographic groups. After excluding other causes of liver disease among the NAFLD cohorts (n=210,660), the impact of sex, race and region on outcomes (mortality, discharge disposition, length of stay [LOS], and cost) were computed using generalized estimating equations (SAS 9.4). RESULTS: Admissions with NAFLD tripled from 2007-2014 at an average rate of 79/100,000 hospitalizations/year (P<0.0001), with a larger rate of increase among males vs. females (83/100,000 vs. 75/100,000), Hispanics vs. Whites vs. Blacks (107/100,000 vs. 80/100,000 vs. 48/100,000), and government-insured or uninsured patients vs. privately-insured (94/100,000 vs. 74/100,000). Males had higher mortality, LOS, and cost than females. Blacks had longer LOS and poorer discharge destination than Whites; while Hispanics and Asians incurred higher cost than Whites. Uninsured patients had higher mortality, longer LOS, and poorer discharge disposition than the privately-insured. CONCLUSIONS: Hospitalizations with NAFLD are rapidly increasing in the US, with a disproportionately higher burden among certain demographic groups. Measures are required to arrest this ominous trend and to eliminate the disparities in outcome among patients hospitalized with NAFLD.

Risk and Outcomes of Clostridium difficile Infection With Chronic Pancreatitis.

OBJECTIVES: Chronic pancreatitis (CP) is associated with high rates of recurrent hospitalizations, which predisposes to Clostridium difficile infection (CDI). We investigate the burden of CDI in CP. METHODS: We identified records of patients with CP from the Nationwide Inpatient Sample (NIS) 2012-2014 and estimated the impact of CDI on their outcomes. We calculated the adjusted odds ratio (AOR) of CP on having CDI (NIS 2014). From NIS 2007-2014, we plotted the trends of CDI and its interaction with CP. RESULTS: From 2012 to 2014, 886 (2.72%) of the 32,614 CP patients had concomitant CDI, which was associated with poorer outcomes: acute kidney injury (AOR, 2.57 [95% confidence interval {CI}, 2.11-3.13]), length of stay (13.3 vs 7.4 days), and charges (US $127,496 vs US $72,767), but not mortality (AOR, 0.93 [95% CI, 0.28-3.05]). In 2014, CP was associated with an increased risk of CDI (crude odds ratio, 2.10 [95% CI, 1.95-2.26]), which persisted after multivariate adjustment (AOR, 2.03 [95% CI, 1.87-2.19]). From 2007 to 2014, the annual prevalence of CDI was 106.4 cases per 10,000 hospitalizations, increasing from 2007 (95.5/10,000) to 2014 (118.4/10,000), with a 3.7 times higher annual rate of increase among CP versus no-CP patients (13.4/10,000 vs 3.7/10,000 population/year). CONCLUSIONS: Chronic pancreatitis patients have high burden of CDI and may benefit from CDI prophylaxis.

Protein Energy Malnutrition Is Associated with Worse Outcomes in Sepsis-A Nationwide Analysis.

BACKGROUND: Protein-energy malnutrition (PEM), resulting from depleted energy and nutrient stores, compromises the body's defense systems and may exacerbate sepsis and its impact. However, population-based studies examining the association of PEM on the prevalence and health-care burden of sepsis are lacking. OBJECTIVE: To investigate the relationship between PEM and sepsis, influence of PEM on clinical outcomes of sepsis, and impact of PEM on trends in sepsis mortality. DESIGN: The primary study is a retrospective cohort analysis of the 2012-2014 National Inpatient Sample (NIS) patient discharge records. Secondary analyses are cross-sectional study on the 2014 NIS and trend analysis on 2007-2014 NIS. PARTICIPANTS/SETTING: The primary study included adult inpatient hospitalizations for sepsis in the United States. MAIN OUTCOME MEASURES: Mortality, complicated sepsis, and 10 other metrics of clinical outcomes and health care utilization. STATISTICAL ANALYSIS: First, patients with sepsis (2014 NIS) were stratified into two groups: uncomplicated (without shock) and complicated (with shock). The adjusted odds ratio of having sepsis (total, uncomplicated, and complicated) was estimated with PEM as predictor using logistic regressions (binomial and multinomial). Second, among patients with sepsis (2012-2014 NIS), PEM cases were matched to cases without PEM (no-PEM) using a greedy-algorithm based propensity-matching methodology (1:1), and the outcomes were measured with conditional regression models. Finally, the trend in mortality from sepsis was calculated, stratified by PEM status, as an effect modifier, using Poisson models (2007-2014 NIS). All models accounted for the complex sampling methodology (SAS 9.4). RESULTS: In 2014, PEM was associated with higher odds for sepsis (3.97 [3.89 to 4.05], P<0.0001) and complicated vs uncomplicated sepsis (1.74 [1.67 to 1.81], P<0.0001). From 2012-2014, about 18% (167,133 of 908,552) of hospitalizations for sepsis had coexisting PEM. After propensity matching, PEM was associated with higher mortality (adjusted odds ratio: 1.35 [1.32 to 1.37], P<0.0001), cost ($160,724 [159,517 to 161,940] vs $86,650 [85,931 to 87,375], P<0.0001), length of stay (14.8 [14.9 to 14.8] vs 8.5 [8.5 to 8.6] days, P<0.0001), adverse events, and resource utilization. Although mortality in sepsis has been trending down from 2007-2014 (-1.19% per year, P trend<0.0001), the decrease was less pronounced among those with PEM vs no-PEM (-0.86% per year vs -1.29% per year, P<0.0001). CONCLUSIONS: PEM is a risk factor for sepsis and associated with poorer outcomes among patients with sepsis. A concerted effort involving all health care workers in the prevention, identification, and treatment of PEM in community-dwelling people before hospitalization might mitigate against these devastating outcomes.

Among inpatients, ischemic bowel disease predisposes to Clostridium difficile infection with concomitant higher mortality and worse outcomes.

BACKGROUND AND AIMS: Clinical conditions resulting in hypoxia, hypoperfusion, anaerobic milieu within the gut, and intestinal epithelial breakdown, such as seen in heart failure, precipitates Clostridium difficile infection (CDI). Given that ischemic bowel disease (IB) typically results in similar changes within the gut, we investigated the relationship between CDI and IB, and the impact of CDI on the clinical outcomes of IB. PATIENTS AND METHODS: We initially performed a cross-sectional analysis on the 2014 Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (NIS) patient's discharge records of ages 18 years and older, by estimating the crude and adjusted odds ratio (aOR) of CDI and IB as the outcome and predictor respectively. We then pooled data from the 2012-2014 NIS, identified, and compared mortality (and 15 other outcomes) between three groups: IB+CDI, IB-alone, and CDI-alone (Statistical Analysis System 9.4). RESULTS: In the 2014 NIS, records with IB (n=27 609), had higher rate and odds of CDI [3.95 vs. 1.17%, aOR: 1.89 (1.77-2.02)] than records without IB (n=5 879 943). The 2012-2014 NIS contained 1105 IB+CDI, 30 960 IB-alone, and 60 758 CDI-alone groups. IB+CDI had higher mortality [aOR: 1.44 (1.11-1.86)], length of stay [9.59 (9.03-10.20) vs. 6.12 (5.99-6.26) days], cost [$93 257 (82 892-104 919) vs. $63 257 (61 029-65 567)], unfavorable discharge disposition [aOR: 2.24 (1.91-2.64)] and poorer results across most of the other outcomes than IB-alone. Comparable results were found for IB+CDI versus CDI-alone. CONCLUSION: IB is a risk factor for CDI in hospitals. CDI is associated with higher mortality, longer length of stay, higher cost, unfavorable discharge, and many other poorer health outcomes in patients with IB.

Effect of aging on A1C levels in individuals without diabetes: evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001-2004.

OBJECTIVE: Although glycemic levels are known to rise with normal aging, the nondiabetic A1C range is not age specific. We examined whether A1C was associated with age in nondiabetic subjects and in subjects with normal glucose tolerance (NGT) in two population-based cohorts. RESEARCH DESIGN AND METHODS: We performed cross-sectional analyses of A1C across age categories in 2,473 nondiabetic participants of the Framingham Offspring Study (FOS) and in 3,270 nondiabetic participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. In FOS, we examined A1C by age in a subset with NGT, i.e., after excluding those with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Multivariate analyses were performed, adjusting for sex, BMI, fasting glucose, and 2-h postload glucose values. RESULTS: In the FOS and NHANES cohorts, A1C levels were positively associated with age in nondiabetic subjects. Linear regression revealed 0.014- and 0.010-unit increases in A1C per year in the nondiabetic FOS and NHANES populations, respectively. The 97.5th percentiles for A1C were 6.0% and 5.6% for nondiabetic individuals aged <40 years in FOS and NHANES, respectively, compared with 6.6% and 6.2% for individuals aged >or=70 years (P(trend) < 0.001). The association of A1C with age was similar when restricted to the subset of FOS subjects with NGT and after adjustments for sex, BMI, fasting glucose, and 2-h postload glucose values. CONCLUSIONS: A1C levels are positively associated with age in nondiabetic populations even after exclusion of subjects with IFG and/or IGT. Further studies are needed to determine whether age-specific diagnostic and treatment criteria would be appropriate.

Clinical predictors of disease progression and medication initiation in untreated patients with type 2 diabetes and A1C less than 7%.

OBJECTIVE: Many patients with early diabetes remain untreated. Our objectives were to identify clinical predictors of 1) worsening glycemic control and 2) medical treatment initiation in response to worsening glycemic control among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We identified 5,804 type 2 diabetic patients seen at least twice between June 2005 and June 2006 within our 12-clinic primary care network. We examined predictors of diabetes progression (A1C >or=7% or initiation of hypoglycemic agent) over a 1-year follow-up period in 705 patients who had A1C <7% and were not on glucose-lowering medications at baseline. In the 200 patients in this group who progressed, we examined predictors of medical therapy initiation. RESULTS: In multivariate analyses, baseline A1C (P < 0.0001), younger age (P = 0.04), and weight gain (P = 0.03) were independent predictors of progression after adjusting for race, sex, and baseline HDL levels. Each decade of increasing age reduced the risk of progression by 15%. Each 1-lb increase in weight was associated with a 2% increased odds of progression. Likelihood of medication initiation among progressors decreased by 40% (P = 0.02) with every decade of age and decreased by 2.3% (P = 0.02) with each 1-mg/dl decrease in LDL level from baseline after adjusting for race, sex, and weight change. CONCLUSIONS: Among untreated primary care patients with type 2 diabetes and A1C <7%, younger patients and those with weight gain were more likely to have diabetes progression and should be the focus of aggressive diabetes management.

Polymorphic susceptibility to the molecular causes of neural tube defects during diabetic embryopathy.

Previously, we demonstrated that neural tube defects (NTDs) are significantly increased in a mouse model of diabetic pregnancy. In addition, expression of Pax-3, a gene encoding a transcription factor required for neural tube development, is significantly decreased. This suggests that diabetic embryopathy results from impaired expression of genes regulating essential morphogenetic processes. Here, we report that in one mouse strain, C57Bl/6J, embryos are resistant to the effects of maternal diabetes on NTDs and Pax-3 expression, in contrast to a susceptible strain, FVB, in which maternal diabetes significantly increases NTDs (P = 0.02) and inhibits Pax-3 expression (P = 0.01). Resistance to NTDs caused by diabetic pregnancy is a dominant trait, as demonstrated by heterozygous embryos of diabetic or nondiabetic mothers of either strain. There was no significant difference between strains in expression of genes that regulate free radical scavenging pathways, suggesting that susceptibility to oxidative stress does not account for the genetic differences. Understanding the genetic bases for differential susceptibility to altered gene expression and NTDs in diabetic mice may be important in delineating the mechanisms by which maternal hyperglycemia interferes with embryo gene expression. Moreover, if susceptibility to diabetic embryopathy is variable in humans as well as in mice, it may be possible to screen individuals at increased risk for this complication of diabetes.

Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis.

Pax-3 is a transcription factor that is expressed in the neural tube, neural crest, and dermomyotome. We previously showed that apoptosis is associated with neural tube defects (NTDs) in Pax-3-deficient Splotch (Sp/Sp) embryos. Here we show that p53 deficiency, caused by germ-line mutation or by pifithrin-alpha, an inhibitor of p53-dependent apoptosis, rescues not only apoptosis, but also NTDs, in Sp/Sp embryos. Pax-3 deficiency had no effect on p53 mRNA, but increased p53 protein levels. These results suggest that Pax-3 regulates neural tube closure by inhibiting p53-dependent apoptosis, rather than by inducing neural tube-specific gene expression.