Risk of hospitalization among patients with epilepsy using long versus short half-life adjunctive antiepileptic drugs.

INTRODUCTION: While antiepileptic drugs (AEDs) remain the primary treatment for epilepsy, many patients continue to have seizures. Uncontrolled seizures may be related to AED half-life, since short half-life (SHL) AEDs require more frequent dosing compared with the simplified regimens of long half-life (LHL) AEDs. Long half-life AEDs may also improve seizure control by extending missed dose forgiveness periods. The value of LHL AEDs may be assessed as reduced healthcare utilization. The study's objective was to examine the impact of adding an LHL versus SHL adjunctive AED on the risk of hospitalizations in patients with uncontrolled epilepsy. METHODS: This was a retrospective, longitudinal cohort study using the Symphony Health Solution Patient Integrated Dataverse. Patients ≥12 years old with uncontrolled epilepsy (≥2 medical claims ≥30 days apart) were identified during a study period (8/1/2012-7/31/2017). Patients were selected if they were subsequently initiated an adjunctive AED (excluding modified release formulations), and the prescription date served as the index. Patients were stratified into two mutually exclusive cohorts based on the index AED half-life (≤20 versus >20 h). Poisson regressions with robust error variances were performed for the relative risks (RRs) of all-cause, epilepsy-related, and injury-related hospitalizations. RESULTS: A total of 4984 patients were identified (2705 in the LHL and 2279 in the SHL cohort). Compared with those in the SHL cohort, patients in the LHL cohort were significantly younger [mean (SD, years): 43.9 (18.5) versus 49.2 (17.2), p < 0.001] and were less comorbid [mean (SD) of Charlson comorbidity index: 1.2 (1.8) versus 1.8 (2.2), p < 0.001]. In the one-year postindex date, adjusting for group differences, the risks of both all-cause and epilepsy-related hospitalizations were significantly lower in the LHL cohort than in the SHL cohort [all-cause: 0.84 (95% CI: 0.76-0.93), p = 0.0006; epilepsy-related: 0.83 (0.73-0.94), p = 0.0046].Injury-related hospitalizations did not differ between LHL and SHL cohorts. CONCLUSION: In patients with uncontrolled epilepsy who were initiated on an adjunctive AED, the choice of an LHL versus SHL was associated with significantly lower risks of all-cause and epilepsy-related hospitalizations.

Direct Costs Associated with Relapsed Diffuse Large B-Cell Lymphoma Therapies.

BACKGROUND: About one third of patients with diffuse large B-cell lymphoma (DLBCL) relapse after receiving first-line (1L) treatment of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Relapsed patients may then be eligible for second-line (2L) therapy. The study's objective was to examine health care use and costs among treated patients with DLBCL receiving 2L therapy versus those without relapse. MATERIALS AND METHODS: We analyzed Truven Health MarketScan® claims data between 2006 and 2015. Patients (≥18 years of age) had ≥1 DLBCL claim from 1 year before to 90 days after beginning 1L therapy, and comprised those without 2L treatment for ≥2 years (cured controls) versus those who initiated non-R-CHOP chemotherapy after discontinuing 1L therapy (2L cohort). 2L patients were further subgrouped: hematopoietic stem cell transplant (HSCT [yes/no]) and time of relapse (months between 1L and 2L): early (≤3), mid (4-12), and late (>12) relapse. The primary outcome was 1- and 2-year health care costs. Hospitalization rate and length of stay were also measured. RESULTS: A total of 1,374 patients with DLBCL received R-CHOP and fulfilled all criteria: 1,157 cured controls and 217 2L patients (87 early-relapse, 66 mid-relapse, 64 late-relapse). Twenty-eight percent of 2L patients received HSCT. Charlson Comorbidity Index/mortality risk was higher for 2L patients (4.2 [SD: 3.0]) versus controls (3.8 [2.6]; p = .039), as were yearly costs (Year 1: $210,488 [$172,851] vs. $25,044 [$32,441]; p < .001 and Year 2: $267,770 [$266,536] vs. $42,272 [$49,281]; p < .001). HSCT and chemotherapy were each significant contributors of cost among 2L patients. CONCLUSION: DLBCL is resource intensive, particularly for 2L patients. Great need exists for newer, effective therapies for DLBCL that may save lives and reduce costs. IMPLICATIONS FOR PRACTICE: This study identified multiple important drivers of cost in the understudied population of patients with diffuse large B-cell lymphoma (DLBCL) receiving second-line (2L) treatment. Such drivers included hematopoietic stem cell transplant (HSCT) and chemotherapy. Even though HSCT is currently the only curative therapy for DLBCL, less than one third of patients receiving 2L and subsequent treatment underwent transplant, which indicates potential underuse. The variation in chemotherapy regimens suggested a lack of consensus for best practices. Further research focusing on newer and more effective treatment options for DLBCL has the potential to decrease mortality, in addition to reducing the extensive costs related to therapy options such as transplant.

Clinically Diagnosed Acute Diverticulitis in Outpatients: Misdiagnosis in Patients with Irritable Bowel Syndrome.

BACKGROUND: Physicians often diagnose diverticulitis and prescribe antibiotics in outpatients with abdominal pain and tenderness without other evidence. AIM: We investigated the misattribution of irritable bowel syndrome (IBS) symptoms to diverticulitis in outpatients. METHODS: In patients diagnosed with diverticulitis and dispensed antibiotics in an integrated healthcare system, we retrospectively compared 15,846 outpatients managed without computed tomography (CT) versus 3750 emergency department/inpatients who had CT. We assessed demographics and past history, including 17 symptom-based somatic and 11 mental disorders and three somatic-mental comorbidity pairs (dyads) coded over 3 years and seven drug classes dispensed over 1 year before diagnosis. RESULTS: Univariate analysis showed small intergroup demographic differences. Outpatients had increases in prior diverticulitis, including outpatient-managed episodes, total somatic diagnoses (p < .0001), eight somatic and three mental disorders (p ≤ .015), all three dyads (p ≤ .05), and dispensing of three drug classes (p ≤ .016). IBS had been diagnosed in 2399 (15.1 %) outpatients versus 361 (9.6 %) emergency department/inpatients (p < .0001), the greatest increase in any comorbidity. Emergency department/inpatients had no somatic comorbidity more often but more alcohol dependence, non-dependent drug abuse, and opioid dispensing (p ≤ .05). Regression analysis revealed outpatient care was independently positively associated with younger age, non-Hispanic white race/ethnicity, less Charlson comorbidity, diverticulitis history, IBS, chest pain, dyspepsia, fibromyalgia, low back pain, migraine, acute reaction to stress, and antispasmodic and anxiolytic dispensing and negatively associated with non-dependent drug abuse and opioid dispensing (p ≤ .0226). CONCLUSIONS: Multiple types of indirect and concordant evidence suggest misattribution of IBS pain to diverticulitis and unnecessary antibiotic therapy in outpatients.

Oesophageal chemoreceptors of blue crabs, Callinectes sapidus, sense chemical deterrents and can block ingestion of food.

Decapod crustaceans such as blue crabs possess a variety of chemoreceptors that control different stages of the feeding process. All these chemoreceptors are putative targets for feeding deterrents that cause animals to avoid or reject otherwise palatable food. As a first step towards characterizing the chemoreceptors that mediate the effect of deterrents, we used a behavioral approach to investigate their precise location. Data presented here demonstrate that chemoreceptors located on the antennules, pereiopods and mouthparts do not mediate the food-rejection effects of a variety of deterrents, both natural and artificial to crabs. Crabs always searched for deterrent-laced food and took it to their oral region. The deterrent effect was manifested as either rejection or extensive manipulation, but in both cases crabs bit the food. The biting behavior is relevant because the introduction of food into the oral cavity ensured that the deterrents gained access to the oesophageal taste receptors, and so we conclude that they are the ones mediating rejection. Additional support comes from the fact that a variety of deterrent compounds evoked oesophageal dilatation, which is mediated by oesophageal receptors and has been linked to food rejection. Further, there is a positive correlation between a compound's ability to elicit rejection and its ability to evoke oesophageal dilatation. The fact that deterrents do not act at a distance is in accordance with the limited solubility of most known feeding deterrents, and likely influences predator-prey interactions and their outcome: prey organisms will be attacked and bitten before deterrents become relevant.

Burden of Nasal Polyps in the United States.

OBJECTIVE: To investigate the clinical and health care burden of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) in the United States. STUDY DESIGN: Retrospective, cross-sectional design with analyses of patient visits from 2 databases. SETTING: National Ambulatory Medical Care Survey (NAMCS, 2012-2016) and State Ambulatory Surgery and Services Databases (SASD, 2012-2015) in available states. METHODS: In each analysis, we identified patients (≥18 years old) with a diagnosis of CRSwNP (ICD-9-CM: 471.x; ICD-10-CM: J33.x) in the visit record during the study period. CRS patients without polyps (CRSsNP: ICD-9-CM: 473.x, ICD-10-CM: J32.x; without CRSwNP codes) were identified for comparison. In the SASD, we focused on visits involving relevant sinus procedures. Outcomes included comorbidities, diagnostic testing, and prescribed medication (NAMCS) and surgery visit characteristics (SASD). RESULTS: We identified 2272 NAMCS records from physician offices (183 CRSwNP, 2089 CRSsNP). Most visits were for patients aged <65 years (78.8%, 80.6%) and privately insured (67.7%, 61.5%); CRSwNP visits had a male majority (56.3%, 35.4%). CRSwNP vs CRSsNP visits more often reported asthma (40.2%, 10.3%), allergic rhinitis (14.0%, 8.7%), and congestion (22.0%, 21.1%), with the use of glucocorticoids (21.0%, 17.7%) and nasal allergy medication (26.2%, 10.2%). In the SASD, 427,306 surgery visits were identified (71,195 CRSwNP, 356,111 CRSsNP); demographics were similar to NAMCS. CRSwNP surgeries involved more sinus types (59.3%, 41.4%). Surgeries were mostly elective (>99%) and completed quickly (<2 hours), without perioperative complications (>99%), followed by routine discharge (>91%); follow-up visits were common (14.9%, 13.9%). CONCLUSION: CRSwNP compared to CRSsNP patients have a distinct clinical experience, with moderately higher medication need and more extensive surgery.

Burden of disease in pediatric narcolepsy: a claims-based analysis of health care utilization, costs, and comorbidities.

BACKGROUND: This study analyzed a privately insured pediatric population with and without narcolepsy to determine the impact of pediatric narcolepsy on comorbidities, health care utilization, and cost. Additional analyses compared narcolepsy type 1 and type 2. METHODS: This retrospective cross-sectional study identified US patients with narcolepsy <18 years of age with ≥2 claims with a diagnosis code of narcolepsy using Truven MarketScan® data 2011 to 2015. Patients were matched to controls without narcolepsy. Comorbid conditions, health care utilization, and costs were measured by calendar year. P values are nominal, and no adjustments for multiplicity or multiple comparisons were made. RESULTS: A total of 1427 pediatric patients with narcolepsy were identified and matched with 4281 controls from 2011 to 2015. Patients with narcolepsy had more comorbid conditions (mean 5.8 vs 2.4, nominal P < 0.001). Respiratory diseases and mood disorders were more common in patients with narcolepsy than controls (57% vs 32% and 56% vs 14%, respectively; both nominal P < 0.001). Compared to controls, patients with narcolepsy underwent more diagnostic tests (electroencephalogram, EEG [0.13 vs 0.0053]) and brain computed tomography, CT/magnetic resonance imaging, MRI (0.26 vs 0.022; both nominal P < 0.001). Mean annual inpatient days (0.71 vs 0.15), emergency department visits (0.51 vs 0.15), and outpatient office visits (8.6 vs 2.3) were higher for patients with narcolepsy than controls (all nominal P < 0.001). Annual mean health care costs were higher for patients with narcolepsy versus controls ($15,797 vs $2449, nominal P < 0.001). CONCLUSION: Pediatric patients with narcolepsy had greater comorbidity, higher health care utilization, and higher costs than patients without narcolepsy.

The Clinical and Economic Burden of Newly Diagnosed Hereditary Transthyretin (ATTRv) Amyloidosis: A Retrospective Analysis of Claims Data.

INTRODUCTION: Little is known about the burden of hereditary transthyretin (ATTRv) amyloidosis, a genetic, progressive, and fatal disease caused by extracellular deposition of transthyretin amyloid fibrils. The study's aim was to estimate costs and disease burden associated with ATTRv amyloidosis in a real-world setting. METHODS: Using IBM® MarketScan® Commercial and Medicare Supplemental data, we identified patients at least 18 years of age with newly diagnosed ATTRv amyloidosis. Diagnosis required at least one medical claim with relevant diagnosis code (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] 277.30-.31, 277.39; ICD-10-CM E85.0-.4, E85.89, E85.9) between January 1, 2014 and December 31, 2016, and at least one additional criterion occurring during study period (2013-2017): at least 15 days diflunisal use without more than a 30-day gap; liver transplant; or claim with codes E85.1 or E85.2. First diagnosis date was study index. Continuous enrollment 1-year pre-index (baseline) and post-index (follow-up) was required. Patients with baseline amyloidosis diagnosis were excluded. Outcomes of interest were comorbidities and 1-year follow-up healthcare utilization and costs (also reported quarterly). RESULTS: Among 185 qualifying patients, mean age was 59.2 years (standard deviation 15.2), 54.1% were female, and baseline Charlson comorbidity index was 2.2 (2.5). Neuropathy (30.3%), diabetes (27.0%), and cardiovascular-related comorbidities, including dyspnea (25.9%) and congestive heart failure (21.6%), were common during follow-up. Nearly a quarter of patients (24.9%) were hospitalized during follow-up. Most hospitalizations and emergency department visits occurred in the first quarter post-diagnosis (18.9%, 17.8%, respectively) and dropped in subsequent quarters. The annual mean total cost was $64,066, with inpatient services contributing the majority of the expenses ($34,461), followed by outpatient ($23,853), and then pharmacy ($5752). As with utilization, costs were highest in the first quarter post-diagnosis and dropped in subsequent quarters. CONCLUSION: Patients newly diagnosed with ATTRv amyloidosis have substantial healthcare utilization and costs in the first year, primarily the initial months, post-diagnosis. Further research should examine later costs associated with disease progression and end-of-life care.

Untangling the clinical and economic burden of hospitalization for cardiac amyloidosis in the United States.

PURPOSE: Cardiac dysfunction is common in amyloid light-chain (AL) amyloidosis, a rare disease caused by extracellular deposition of misfolded immunoglobulin light chains. This study aimed to examine economic/clinical disease burden in hospitalized cardiac amyloidosis patients. PATIENTS AND METHODS: Cardiac amyloidosis patients ≥18 years old hospitalized between 2014 and 2016 were identified in claims if they had ≥1 inpatient claim consistent with amyloidosis and evidence of cardiac dysfunction. Descriptive statistics were reported. RESULTS: 3239 cardiac amyloidosis patients [1795 (55.4%) with concurrent renal disease] were identified. Mean (SD) length of stay was 8.3 (11.1) days. 25.2% were admitted to the intensive care unit. Mean overall hospitalization costs were USD$20,584. In-hospital mortality was 9.0% overall. 16.8% were readmitted within 30 days, with 11.2% dying in-hospital and a mean readmission cost of USD$18,536. CONCLUSION: Hospitalization for cardiac amyloidosis is costly, with high rates of readmission and mortality. Opportunities exist to improve care.

Weight gain changes in patients with aripiprazole monotherapy compared with aripiprazole-antidepressant polypharmacy in an outpatient sample.

OBJECTIVE: This study seeks to evaluate the weight gain effect within a community-based population of patients with diagnoses of depression, mood disorder, and schizophrenia receiving aripiprazole over a period of at least 6 months. METHOD: The four million members of Kaiser Permanente of Southern California (KPSC) were queried for a four-year period between January 1, 2010 and December 31, 2013. The initial cohort comprised 25,682 KPSC members who received at least one dispense of aripiprazole. This initial cohort was split into those who received aripiprazole as a monotherapy ("Alone" group) and those who were given aripiprazole as part of a combination therapy. The group of patients that received aripiprazole and antidepressant with high serotonin reuptake inhibition we called "High" group while the group receiving aripiprazole and bupropion combination we called "Low" serotonin group. We compared the primary endpoint of mean percent weight change from baseline after 180 days of continuous treatment between the three groups. Three pairwise comparisons were made: High versus Alone, Low versus Alone, and Low versus High, using adjusted and unadjusted linear regression models. RESULTS: Within this population, patients on aripiprazole monotherapy showed statistically significant weight gain in all three groups. However, there was no statistically significant difference in weight gain between the aripiprazole monotherapy, the high serotonergic combination group, and the low serotonergic combination group. This finding applied even within the subset of patients who were considered obese (body mass index > 30). CONCLUSIONS: The results suggest that weight gain is unchanged by combination treatments, but further research is required.

Mindfulness-Based Cognitive Therapy for Patients With Depression Decreases the Need for Outpatient Visits.

OBJECTIVE: To determine if the use of mindfulness-based cognitive therapy (MBCT) in patients with a history of 2 or more episodes of major depressive disorder and other mood disorders will decrease the need for medication management and other interventions and will also decrease the need for outpatient services and the overall cost of treatment. METHODS: The study patients completed MBCT group sessions between January 1, 2010, and December 31, 2013. Patients who had 2 or more episodes of major depressive disorder (recurrent MDD) were categorized into a group. The remaining patients with other mood disorders were placed in a comparison group. The mean differences in drug treatments and hospital utilizations between the recurrent MDD and nonrecurrent MDD group were compared. Wald P values and 95% CIs were obtained for both adjusted and unadjusted estimated mean differences. Covariates were adjusted for age at start of MBCT, gender, and race/ethnicity. RESULTS: The final sample consisted of 142 patients (93 recurrent MDD and 49 others). There was no significant difference in the effect of MBCT on medication changes between recurrent MDD patients and nonrecurrent MDD patients. Recurrent MDD patients who participated in MBCT experienced reduction in all calls and visits (P = .0068) and less psychiatric visits (P = .0026) in the year after MBCT when compared with the visits before the intervention. CONCLUSIONS: This study evaluated the effectiveness of MBCT in reducing the need for additional psychiatric services. The study evaluated patients who received MBCT over 3 years and demonstrated that MBCT decreased the need for care regardless of medication changes. The results raise the question of whether MBCT allows patients to respond to situations more skillfully or if MBCT itself decreases depressive symptoms. The limitations of this study include a small sample size, patient selection, and its design as a retrospective study. However, this study may have implications as a treatment strategy that may be generalizable to other clinics and patient populations.

Gestational Diabetes Screening: The International Association of the Diabetes and Pregnancy Study Groups Compared With Carpenter-Coustan Screening.

OBJECTIVE: To evaluate whether one-step gestational diabetes screening recommended by The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) is associated with better maternal, perinatal, or neonatal outcomes than the two-step Carpenter-Coustan screening. METHODS: In this before-after retrospective cohort study conducted between July 1, 2010, and December 31, 2013, we compared Carpenter-Coustan and IADPSG screening in patients with singleton pregnancies. All patients diagnosed with gestational diabetes received intensive teaching, home glucose monitoring, and medications as indicated. The primary outcome was the rate of large-for-gestational-age neonates. Secondary outcome measures were macrosomia (greater than 4,000 g), primary cesarean delivery, neonatal intensive care unit admission, preterm delivery, preeclampsia, and hyperbilirubinemia. We determined that a sample size of 2,782 per group was sufficient to detect a 2% difference in the primary outcome between groups with 80% power assuming a 10% incidence in the before group. The groups were compared using Fisher exact test for proportions and a χ test for odds ratios. RESULTS: In the before (Carpenter-Coustan) group, 513 (17%) of the 2,972 patients were diagnosed with gestational diabetes, and in the after (IADPSG) group, 847 (27%) of the 3,094 patients were so diagnosed (P<.001). There was no significant difference in rates of large for gestational age, 10% and 9%, respectively (P=.25). The IADPSG group had a significantly higher primary cesarean delivery rate-16% compared with 20% (P<.001), but there were no significant differences in any other pregnancy outcomes. CONCLUSION: Although one-step screening was associated with more patients being treated for gestational diabetes, it was not associated with a decrease in large-for-gestational-age or macrosomic neonates but was associated with an increased rate of primary cesarean delivery. Our results did not support the IADPSG-recommended screening protocol.

Stem cell niche dynamics: from homeostasis to carcinogenesis.

The stem cell microenvironment is involved in regulating the fate of the stem cell with respect to self-renewal, quiescence, and differentiation. Mathematical models are helpful in understanding how key pathways regulate the dynamics of stem cell maintenance and homeostasis. This tight regulation and maintenance of stem cell number is thought to break down during carcinogenesis. As a result, the stem cell niche has become a novel target of cancer therapeutics. Developing a quantitative understanding of the regulatory pathways that guide stem cell behavior will be vital to understanding how these systems change under conditions of stress, inflammation, and cancer initiation. Predictions from mathematical modeling can be used as a clinical tool to guide therapy design. We present a survey of mathematical models used to study stem cell population dynamics and stem cell niche regulation, both in the hematopoietic system and other tissues. Highlighting the quantitative aspects of stem cell biology, we describe compelling questions that can be addressed with modeling. Finally, we discuss experimental systems, most notably Drosophila, that can best be used to validate mathematical predictions.