Rising Inpatient Encounters and Economic Burden for Patients with Nonalcoholic Fatty Liver Disease in the USA.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the fastest-growing chronic liver disease. However, little is known about NAFLD inpatient resource utilization and clinical outcomes. AIMS: The aim of this study was to quantify inpatient NAFLD encounters using patient-level data over time. METHODS: This was a retrospective analysis of de-identified data for NAFLD patients from the California Patient Discharge Database from 2006 to 2013. NAFLD patients were identified by ICD9 codes 571.40, 571.41, 571.49, 571.8, and 571.9. RESULTS: NAFLD patients (n = 91,558) were predominantly female (60%), 45-65 years old (44%), and white (53%). Inpatient encounters increased from 8153 in 2006 to 16,457 in 2013 and were associated with a 207% increase in charges ($686 million in 2006 to $1.42 billion in 2013) and average increase in charges of 9.8% per year adjusting for inflation. Comorbidities (obesity, diabetes, hyperlipidemia, cardiovascular disease, other cancer, and renal disease) increased significantly over time (all P < 0.05). From 2006 to 2011, there were 11,463 deaths (1849 for liver-related hospitalizations) (mean follow-up 4.00 ± 2.13 years). The most significant predictors of death were age > 75 (aHR 3.9, P < 0.0001), male gender (aHR 1.10, P < 0.0001), white race (aHR 1.2, P < 0.0001), decompensated cirrhosis (aHR 2.1, P < 0.0001), and cancer other than HCC (aHR 3.2, P < 0.0001). Within the liver-related hospitalization cohort, mortality predictors were similar, except for Hispanic race (aHR 0.92, P < 0.0096) and renal disease (aHR 1.50, P < 0.0001). CONCLUSIONS: The number of NAFLD inpatient encounters increased significantly from 2006 to 2013, as did the inflation-adjusted inpatient charges. The most significant predictors of death were non-liver cancers (HR 3.11, P < 0.0001, CI 3.06-3.16) and age > 75 years (HR 3.94, P < 0.0001, HR 3.86-4.03).

PKCι is a target of 7,8,4'-trihydroxyisoflavone for the suppression of UVB-induced MMP-1 expression.

The soy isoflavone daidzein is bioconverted to 7,8,4'-trihydroxyisoflavone (7,8,4'-THIF) by microorganisms. Here, we investigated the matrix metalloproteinase (MMP)-1 inhibitory properties of 7,8,4'-THIF that arise through the suppression of UVB-induced MMP-1 expression. 7,8,4'-THIF reduced UVB-induced MMP-1 expression at the transcriptional level in primary human dermal fibroblasts and inhibited UVB-induced transcriptional activity of AP-1, a major activator of MMP-1 expression. Additionally, it was observed that the mitogen-activated protein kinase (MAPK) pathway, a crucial signalling cascade for MMP-1 expression, was suppressed by 7,8,4'-THIF. Protein kinase C iota (PKCι) was suspected to be a direct target of 7,8,4'-THIF. The direct interaction between 7,8,4'-THIF and PKCι was confirmed using pull-down assays and immobilized metal ion affinity-based fluorescence polarization assays. Finally, we observed that 7,8,4'-THIF inhibited UVB-induced MMP-1 expression in a human skin equivalent model. Taken together, these results suggest that 7,8,4'-THIF, a bioconversion product of daidzein, suppresses UVB-induced MMP-1 expression.

Physician perspectives on the management of viral hepatitis and hepatocellular carcinoma in Myanmar.

BACKGROUND: In Myanmar, over five million people are infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). Hepatitis has been a recent focus with the development of a National Strategic Plan on Hepatitis and plans to subsidize HCV treatment. METHODS: During a two-day national liver disease symposium covering HCV, HBV, hepatocellular (HCC), and end-stage liver disease (ESLD), physician surveys were administered using the automated response system (ARS) to assess physician knowledge, perceptions of barriers to screening and treatment, and proposed solutions. Multivariate logistic regression was used to estimate odds ratio (OR) relating demography and practice factors with higher provider knowledge and improvement. RESULTS: One hundred two physicians attending from various specialty areas (31.0% specializing in gastroenterology/hepatology and/or infectious disease) were of mixed gender (46.8% male), were younger than or equal to 40 years old (51.1% 20 to 40 years), had less experience (61.6% with ≤10 years of medical practice), were from the metropolitan area of Yangon (72.1%), and saw <10 liver disease patients per week (74.3%). The majority of physicians were not comfortable with treating or managing patients with liver disease. The post-test scores demonstrated an improvement in liver disease knowledge (9.0% ± 27.0) compared to the baseline pre-test scores; no variables were associated with significant improvement in hepatitis knowledge. Physicians identified the cost of diagnostic blood tests and treatment as the most significant barrier to treatment. Top solutions proposed were universal screening policies (46%), removal of financial barriers for treatment (29%), patient education (14%) and provider education (11%). CONCLUSIONS: Physician knowledge improved after this symposium, and many other needs were revealed by the physician input on barriers to care and their solutions. These survey results are important in guiding the next steps to improve liver disease management and future medical education efforts in Myanmar.

Patient-Centered Home Care Using Digital Medicine and Telemetric Data for Hypertension: Feasibility and Acceptability of Objective Ambulatory Assessment.

Objective information that can be passively obtained in an ambulatory setting could be potentially useful for determining appropriate care in blood pressure (BP) management. This study utilized digital medicine (DM) prototypes and telemetric data acquisition to directly confirm medication use and to assess habits of daily living in a hypertensive population. Thirty-seven patients (23 men age 62±9 years) used the system for 6 weeks. DM prototypes consisted of valsartan 80 mg or 160 mg placed in a gelatin hemicapsule with an excipient tablet as a "stopper," with a poppy seed-sized ingestible sensor (IS) made of foodstuff on its external surface and capable of creating a biogalvanic current on ingestion to alert a wearable sensor (WS) that was worn on the torso. Passive data collection included IS ingestion dates and times, daily step count, BP, and weight. Automatic short message service (SMS) reminders were sent whenever BP or weight values were not received. Passive detection of DM ingestion was 98% when compared with directly observed dosing. Mean taking and timing adherence rates were 90% and 83%, respectively, and the average step count at a pace of ≥60 steps per minute was 2.0±1.5 h/d. An automatic SMS was sent and 100% confirmed for 251 BP and 14 weight values that were not received. Mild and transient WS-related skin irritation was the most common device-related adverse event. There were no serious or unanticipated adverse events. Ninety percent of patients did not mind swallowing a DM capsule, and 75% had a positive overall experience with the system. Ambulatory evaluation of medication adherence and habits of daily living appear to be feasible and acceptable using DM and passive acquisition of telemetric data.

Screening and management of viral hepatitis and hepatocellular carcinoma in Mongolia: results from a survey of Mongolian physicians from all major provinces of Mongolia.

BACKGROUND: According to Globocan, Mongolia has the highest worldwide hepatocellular carcinoma (HCC) incidence (78.1/100 000, 3.5× higher than China). AIMS AND METHODS: We conducted an anonymous survey of physicians from major provinces who attended an educational liver symposium, analysing their demography, practice, knowledge, perceptions and proposed solutions. Multivariate logistic regression was used to estimate OR relating demography and practice factors with higher provider knowledge and improvement. RESULTS: Of the 121 attendees, 44-95 (36-79%) responded to each question. Most were female (87%), young (79% age <50), subspecialists (81%), university-affiliated (74%), and practised in urban areas (61%). The mean pretest and post-test scores per physician were 60.4±20.4 and 65.6±21.3, with no observed significant predictors for baseline knowledge or improvement. Most (>80%) noted that <50% of patients who need hepatitis or HCC screening receive it. The main perceived barriers to screening were inability to pay for tests, lack of guidelines and poor patient awareness. Hepatitis treatment rates were low; 83% treated hepatitis C virus in <10 patients in the past year, and 86% treated hepatitis B virus in <10 patients/month. Treatment barriers were multifactorial, with cost as a principal barrier. Proposed solutions were universal screening policies (46%), removal of financial barriers (28%) and provider education (20%). CONCLUSIONS: Physicians from major regions of Mongolia noted low screening for viral hepatitis, even lower treatment rates, financial barriers and the need for increased educational efforts. We advocate broad-based medical education tailored to local needs and based on needs assessment and outcome measurements.

Rutin inhibits B[a]PDE-induced cyclooxygenase-2 expression by targeting EGFR kinase activity.

Rutin is a well-known flavonoid that exists in various natural sources. Accumulative studies have represented the biological effects of rutin, such as anti-oxidative and anti-inflammatory effects. However, the underlying mechanisms of rutin and its direct targets are not understood. We investigated whether rutin reduced B[a]PDE-induced-COX-2 expression. The transactivation of AP-1 and NF-κB were inhibited by rutin. Rutin also attenuated B[a]PDE-induced Raf/MEK/ERK and Akt activation, but had no effect on the phosphorylation of EGFR. An in vitro kinase assay revealed rutin suppressed EGFR kinase activity. We also confirmed direct binding between rutin and EGFR, and found that the binding was regressed by ATP. The EGFR inhibitor also inhibited the B[a]PDE-induced MEK/ERK and Akt signaling pathways and subsequently, suppressed COX-2 expression and promoter activity, in addition to suppressing the transactivation of AP-1 and NF-κB. In EGFR(-/-)mouse embryonic fibroblast cells, B[a]PDE-induced COX-2 expression was also diminished. Collectively, rutin inhibits B[a]PDE-induced COX-2 expression by suppressing the Raf/MEK/ERK and Akt signaling pathways. EGFR appeared to be the direct target of rutin.

Retrospective evaluation of the impact of copayment increases for specialty medications on adherence and persistence in an integrated health maintenance organization system.

BACKGROUND: Specialty drugs are generally defined as high-cost injectable, infused, oral, or inhaled drugs that require close monitoring. Specialty drugs account for an increasing percentage of total drug expenditures, and management of specialty drugs has become a priority. A Central Texas-based integrated health maintenance organization system implemented a specialty drug benefit to manage expensive specialty drug costs. OBJECTIVES: Our objective was to measure and compare the change in adherence and persistence after implementation of copayment increases for select specialty medications used on a long-term basis (at least 2 years). METHODS: Patients who were long-term users of anti-inflammatory, immunosuppressant, cancer, and multiple sclerosis medications were selected. The intervention group consisted of those whose out-of-pocket payment for specialty medications increased, and the control group consisted of those whose out-of-pocket costs did not change. Adherence, defined by proportion of days covered, was measured every 3 months for 12 months before and after the change. Individual growth model analysis evaluated the changes in adherence. Cox regression analysis determined the difference in persistence between groups. RESULTS: There were 178 and 202 patients in the intervention and control groups, respectively. The growth model showed a small but statistically significant decrease in proportion of days covered of 0.040 after copay changes in the intervention versus control group (P < 0.001) for immunosuppressants. The Cox regression analysis indicated a higher probability of intervention patients on anti-inflammatory drugs (hazard ratio [HR] = 2.53; 95% CI, 1.38-4.62) and immunosuppressants (HR = 3.01; 95% CI, 1.20-7.56) would be nonpersistent compared with those in their control groups. CONCLUSIONS: The move to the specialty formulary allows for closer scrutiny of specialty utilization by pharmacists, who actively monitor utilization and access. Despite the minimal adherence decrease and significant persistence changes with certain drug types, the results indicated relatively more stability with specialty drug use than reported with traditional pharmaceuticals.

Evaluation of value-based insurance design with a large retail employer.

OBJECTIVES: To measure adherence and assess medical utilization among employees enrolled in a disease management (DM) program offering copayment waivers (value-based insurance design [VBID]). STUDY DESIGN: Retrospective matched case control study. METHODS: Cases were defined as those enrolled in DM, of whom 800 received health education mailings (HEMs) and 476 received telephonic nurse counseling (NC). Controls were eligible for the DM program but did not enroll. Cases and controls were matched 1:1 based on propensity score (n = 2552). Adherence, defined by proportion of days covered, was calculated for 4 diseases using incurred drug claims 1 year before and after the DM program was implemented. Unadjusted and adjusted linear regression compared changes in adherence. Costs and utilization were compared at 1 year and 1.5 years after versus 1 year before implementation. RESULTS: Members receiving NC had improved adherence for antihypertensives, diabetes medications, and statins (ß = 0.050, P = .025; ß = 0.108, P < .001; ß = 0.058, P = .017). Members receiving HEMs had improved adherence only for diabetes medications (ß = 0.052, P = .019). Total healthcare costs for NC members increased by $44 ± $467 versus $1861 ± $401 per member per year (PMPY) for controls (P = .003) at 1.5 years post-implementation. Total healthcare costs for HEM members significantly increased ($1261 ± $199 vs $182 ± $181 PMPY for controls; P < .001) at 1.5 years. CONCLUSION: VBID may be effective in improving medication adherence and reducing total healthcare costs when active counseling is provided to high utilizers of care.

Chromosomal clustering and GATA transcriptional regulation of intestine-expressed genes in C. elegans.

We used mRNA tagging to identify genes expressed in the intestine of C. elegans. Animals expressing an epitope-tagged protein that binds the poly-A tail of mRNAs (FLAG::PAB-1) from an intestine-specific promoter (ges-1) were used to immunoprecipitate FLAG::PAB-1/mRNA complexes from the intestine. A total of 1938 intestine-expressed genes (P<0.001) were identified using DNA microarrays. First, we compared the intestine-expressed genes with those expressed in the muscle and germline, and identified 510 genes enriched in all three tissues and 624 intestine-, 230 muscle- and 1135 germ line-enriched genes. Second, we showed that the 1938 intestine-expressed genes were physically clustered on the chromosomes, suggesting that the order of genes in the genome is influenced by the effect of chromatin domains on gene expression. Furthermore, the commonly expressed genes showed more chromosomal clustering than the tissue-enriched genes, suggesting that chromatin domains may influence housekeeping genes more than tissue-specific genes. Third, in order to gain further insight into the regulation of intestinal gene expression, we searched for regulatory motifs. This analysis found that the promoters of the intestine genes were enriched for the GATA transcription factor consensus binding sequence. We experimentally verified these results by showing that the GATA motif is required in cis and that GATA transcription factors are required in trans for expression of these intestinal genes.