Complete genome analysis of Lactobacillus fermentum YLF016 and its probiotic characteristics.

Lactobacillus fermentum (L. fermentum) YLF016 is a well-characterized probiotic with several favorable characteristics. This study aimed to analyze the probiotic characteristics of L. fermentum and uncover the genes implicated in its potential probiotic ability on the base of its genomics features. The complete genome of L. fermentum YLF016 was found to have a circular chromosome of 2,094,354 bp, and 51.46% G + C content without any plasmid. Its chromosome contained 2,130 predicted protein-encoding genes, 58 tRNA, and 15 rRNA-encoding genes. Also, it was found to have many other probiotic properties, such as a high survival rate in the gastrointestinal tract with strong adherence to intestinal cells, antibacterial activity against pathogens, and antioxidant activity. Moreover, the genome sequence analysis demonstrated specific genes coding for carbon metabolism pathway, genetic adaption, stress resistance, and adhesive ability. Further analysis revealed its non-hemolytic activity and its non-functional ability of virulence factors. In conclusion, L. fermentum YLF016 possesses many valuable probiotic properties that refer to its potential probiotic ability.

Chronic Medication Nonadherence and Potentially Preventable Healthcare Utilization and Spending Among Medicare Patients.

BACKGROUND: The association between nonadherence to chronic medications and potentially preventable healthcare utilization and spending is largely unknown. OBJECTIVES: To examine the associations of chronic medication nonadherence with potentially preventable utilization and spending among patients who were prescribed diabetic medications, renin-angiotensin system antagonists (RASA) for hypertension, or statins for high cholesterol, and compare the associations by patient race/ethnicity and socioeconomic status. DESIGN: Retrospective cohort study. Medicare fee-for-service claims data from 2013 to 2016 for 177,881 patients. MEASURES: Medication nonadherence was defined as having a below 80% proportion of days covered in each 6-month interval after the index prescription. Potentially preventable utilization was measured by preventable emergency department visits and preventable hospitalizations. Potentially preventable spending was calculated as the geographically adjusted spending associated with preventable encounters. RESULTS: After adjustment for other patient characteristics, medication nonadherence was associated with a 1.7-percentage-point increase (95% confidence interval [CI]: 1.4 to 2.0 percentage points, p < 0.001) in the probability of preventable utilization among the diabetic medication cohort, a 1.7-percentage-point increase (95% CI: 1.5 to 1.9 percentage points, p < 0.001) among the RASA cohort, and a 1.0-percentage-point increase (95% CI: 0.8 to 1.1 percentage points, p < 0.001) among the statin cohort. Among patients with at least one preventable encounter, medication nonadherence was associated with $679-$898 increased preventable spending. The incremental probability of preventable utilization and incremental spending associated with nonadherence were higher among racial/ethnic minority and low socioeconomic groups. CONCLUSIONS: Improving medication adherence is a potential avenue to reducing preventable utilization and spending. Interventions are needed to address racial/ethnic and socioeconomic disparities.

Prenatal substance use policies and newborn health.

We study the effect of punitive and priority treatment policies relating to illicit substance use during pregnancy on the rate of neonatal drug withdrawal syndrome, low birth weight, low gestational age, and prenatal care use. Punitive policies criminalize prenatal substance use, or define prenatal substance exposure as child maltreatment in child welfare statutes or as grounds for termination of parental rights. Priority treatment policies are supportive and grant pregnant women priority access to substance use disorder treatment programs. Our empirical strategy relies on administrative data from 2008 to 2018 and a difference-in-differences framework that exploits the staggered implementation of these policies. We find that neonatal drug withdrawal syndrome increases by 10%-18% following the implementation of a punitive policy. This growth is accompanied by modest reductions in prenatal care, which may reflect deterrence from healthcare utilization. In contrast, priority treatment policies are associated with small reductions in low gestational age (2%) and low birth weight (2%), along with increases in prenatal care use. Taken together, our findings suggest that punitive approaches may be associated with unintended adverse pregnancy outcomes, and that supportive approaches may be more effective for improving perinatal health.

USP7 sustains an active epigenetic program via stabilizing MLL2 and WDR5 in diffuse large B-cell lymphoma.

Activated B-cell-like (ABC)-diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin's lymphoma with poor prognosis. The survival of ABC-DLBCL relies on constitutive activation of BCR signaling, but the underlying molecular mechanism is not fully addressed. By mining The Cancer Genome Atlas database, we found that the expression of ubiquitin-specific protease 7 (USP7) is significantly elevated in three cancer types including DLBCL. Interestingly, unlike germinal center B-cell-like (GCB)-DLBCL, ABC-DLBCL shows upregulated expression of USP7. Inhibiting the enzymatic activity of USP7 (P22077) has a drastic effect on ABC-DLBCL, but not GCB-DLBCL cells. Compared to GCB-DLBCL, ABC-DLBCL cells show transcriptional upregulation of multiple components of BCR-signaling. USP7 inhibition significantly reduces the expression of upregulated components of BCR signaling. Mechanistically, USP7 inhibition greatly reduces the methylation of histone 3 on lysine 4 (H3K4me2), which is an epigenetic marker for active enhancers. USP7 inhibition greatly reduces the protein level of WDR5 and MLL2, key components of lysine-specific methyltransferase complex (complex of proteins associated with Set1 [COMPASS]). In ABC-DLBCL cells, USP7 stabilizes WDR5 and MLL2. In patients, the expression of USP7 is significantly associated with components of BCR signaling (LYN, SYK, BTK, PLCG2, PRKCB, MALT1, BCL10, and CARD11) and targets of BCR signaling (MYC and IRF4). In summary, we demonstrated an essential role of USP7 in ABC-DLBCL by organizing an oncogenic epigenetic program via stabilization of WDR5 and MLL2. Targeting USP7 might be a novel and efficient approach to treat patients with ABC-DLBCL and it might be better than targeting individual components such as BTK in BCR signaling.

Prescription Opioids Dispensed to Patients with Cancer with Bone Metastasis: 2011-2017.

Opioid therapy is a first-line approach for moderate-to-severe pain associated with cancer with bone metastasis (CBM). The decade-long decline in opioid prescribing in the U.S. would not be expected to affect patients with CBM. We investigated trends in opioids dispensed to patients with CBM using data from a large commercial claims database. From 2011 quarter 2 to 2017 quarter 4, the percentage of patients with CBM prescribed at least 1 day of opioids in a quarter declined from 28.1% to 24.5% (p < .001) for privately insured patients aged 18-64 years and from 39.1% to 30.5% (p < .001) for Medicare Advantage (MA) patients aged 65 years or older. Among patients with at least 1 day of opioids in a quarter, the average morphine milligram equivalents dispensed declined by 37% and 11% (p < .001 for both) for privately insured and MA patients, respectively. Our findings raise concerns about potential unintended consequences related to population-level reduction in opioid prescribing.

Hepatitis C Treatment by Nonspecialist Providers in the Direct-acting Antiviral Era.

BACKGROUND: Hepatitis C virus (HCV) remains under-treated in the United States and treatment by nonspecialist providers can expand access. We compare HCV treatment provision and treatment completion between nonspecialist and specialist providers. METHODS: This retrospective study used claims data from the Healthcare Cost Institute from 2013 to 2017. We identified providers who prescribed HCV therapy between 2013 and 2017, and patients enrolled in private insurance or Medicare Advantage who had pharmacy claims for HCV treatment. We measured HCV treatment completion, determined based on prescription fills for the minimum expected duration of the antiviral regimen. Using propensity score-weighted regression, we compared the likelihood of early treatment discontinuation by the type of treating provider. RESULTS: The number of providers prescribing HCV treatment peaked in 2015 and then declined. The majority were gastroenterologists, although the proportion of general medicine providers increased to 17% by 2017. Among the 23,463 patients analyzed, 1008 (4%) discontinued before the expected minimum duration. In the propensity score-weighted analysis, patients treated by general medicine physicians had similar odds of treatment discontinuation compared with those treated by gastroenterologists [odds ratio (OR)=1.00, 95% confidence interval (CI): 0.99-1.01, P=0.45]. Results were similar when comparing gastroenterologists to nonphysician providers (OR=1.00, 95% CI: 0.99-1.01, P=0.53) and infectious diseases specialists (OR=1.00, 95% CI: 0.99-1.01, P=0.71). CONCLUSIONS: HCV treatment providers remain primarily gastroenterologists, even in the current simplified treatment era. Patients receiving treatment from general medicine or nonphysician providers had a similar likelihood of treatment completion, suggesting that removing barriers to the scale-up of treatment by nonspecialists may help close treatment gaps for hepatitis C.

Effect of an Electronic Health Record "Nudge" on Opioid Prescribing and Electronic Health Record Keystrokes in Ambulatory Care.

BACKGROUND: Multiple policy initiatives encourage more cautious prescribing of opioids in light of their risks. Electronic health record (EHR) redesign can influence prescriber choices, but some redesigns add to workload. OBJECTIVE: To estimate the effect of an EHR prescribing redesign on both opioid prescribing choices and keystrokes. DESIGN: Quality improvement quasi-experiment, analyzed as interrupted time series. PARTICIPANTS: Adult patients of an academic multispecialty practice and a federally qualified health center (FQHC) who received new prescriptions for short-acting opioids, and their providers. INTERVENTION: In the redesign, new prescriptions of short-acting opioids defaulted to the CDC-recommended minimum for opioid-naïve patients, with no alerts or hard stops, such that 9 keystrokes were required for a guideline-concordant prescription and 24 for a non-concordant prescription. MAIN MEASURES: Proportion of guideline-concordant prescriptions, defined as new prescriptions with a 3-day supply or less, calculated per 2-week period. Number of mouse clicks and keystrokes needed to place prescriptions. KEY RESULTS: Across the 2 sites, 22,113 patients received a new short-acting opioid prescription from 821 providers. Before the intervention, both settings showed secular trends toward smaller-quantity prescriptions. At the academic practice, the intervention was associated with an immediate increase in guideline-concordant prescriptions from an average of 12% to 31% of all prescriptions. At the FQHC, about 44% of prescriptions were concordant at the time of the intervention, which was not associated with an additional significant increase. However, total keystrokes needed to place the concordant prescriptions decreased 62.7% from 3552 in the 6 months before the intervention to 1323 in the 6 months afterwards. CONCLUSIONS: Autocompleting prescription forms with guideline-recommended values was associated with a large increase in guideline concordance in an organization where baseline concordance was low, but not in an organization where it was already high. The redesign markedly reduced the number of keystrokes needed to place orders, with important implications for EHR-related stress. TRIAL REGISTRATION: www.ClinicalTrials.gov protocol 1710018646.

State Policies for Prescription Drug Monitoring Programs and Adverse Opioid-related Hospital Events.

BACKGROUND: State policies to optimize prescriber use of Prescription Drug Monitoring Programs (PDMPs) have proliferated in recent years. Prominent policies include comprehensive mandates for prescriber use of PDMP, laws allowing delegation of PDMP access to office staff, and interstate PDMP data sharing. Evidence is limited regarding the effects of these policies on adverse opioid-related hospital events. OBJECTIVE: The objective of this study was to assess the effects of 3 PDMP policies on adverse opioid-related hospital events among patients with prescription opioid use. RESEARCH DESIGN: We examined 2011-2015 data from a large national commercial insurance database of privately insured and Medicare Advantage patients from 28 states with fully operating PDMPs by the end of 2010. We used a difference-in-differences framework to assess the probabilities of opioid-related hospital events and association with the implementation of PDMP policies. The analysis was conducted for adult patients with any prescription opioid use, a subsample of patients with long-term prescription opioid use, and stratified by older (65+) versus younger patients. RESULTS: Comprehensive use mandates were associated with a relative reduction in the probability of opioid-related hospital events by 28% among patients with any opioid and 21% among patients with long-term opioid use. Such reduction was greater (in relative terms) among older patients despite the lower rate of these events among older than younger patients. Delegate laws and interstate data sharing were associated with limited change in the outcome. CONCLUSION: Comprehensive PDMP use mandates were associated with meaningful reductions in opioid-related hospital events among privately insured and Medicare Advantage adults with prescription opioid use.

State Opioid Limits and Volume of Opioid Prescriptions Received by Medicaid Patients.

BACKGROUND: Since early 2016, an increasing number of states passed legislations that limit the duration and/or dosage of initial opioid prescriptions or opioids for acute pain. OBJECTIVE: The objective of this study was to assess changes in the number of opioid prescriptions covered by Medicaid and received by Medicaid patients associated with state implementation of legislative limits on initial opioid prescriptions. RESEARCH DESIGN: We explored the natural experiment resulting from the staggered implementation of state legislative limits. The analysis adopted a Difference-in-Differences framework and controlled for other major state policies bearing implications for prescription opioid use. The main analysis included 26 states that implemented limits from early 2016 to late 2018. A secondary analysis included all 50 states and the District of Columbia. MEASURES: Population-adjusted state-quarter level counts of Schedule II and III opioid prescriptions received by Medicaid patients, based on data from the Medicaid State Drug Utilization Data and state Medicaid enrollment reports for 2013-2018. RESULTS: Implementation of legislative limits on initial opioid prescriptions was associated with a 7% reduction in the number of opioid prescriptions per 100 Medicaid enrollees. Such reduction was largely attributable to a reduction in Schedule II opioid prescriptions. Secondary analysis by including all jurisdictions and sensitivity checks supported the robustness of results. CONCLUSION: The recent implementation of state legislative limits on initial opioid prescriptions was associated with meaningful reductions in the volume of Schedule II opioid prescriptions received by Medicaid patients.

Can artificial intelligence help identify elder abuse and neglect?

A health care encounter is a potentially critical opportunity to detect elder abuse and initiate intervention. Unfortunately, health care providers currently very seldom identify elder abuse. Through development of advanced data analytics techniques such as machine learning, artificial intelligence has the potential to dramatically improve elder abuse identification in health care settings.

State Medicaid Hepatitis C Treatment Eligibility Criteria and Use of Direct-Acting Antivirals.

Medicaid program criteria for accessing hepatitis C treatment are changing. Medicaid drug utilization data from 2014 to 2016 show that programs that have relaxed their criteria have seen significant increases in treatment utilization, as have states with Medicaid expansions.

First Opioid Prescription and Subsequent High-Risk Opioid Use: a National Study of Privately Insured and Medicare Advantage Adults.

BACKGROUND: National guidelines make recommendations regarding the initial opioid prescriptions, but most of the supporting evidence is from the initial episode of care, not the first prescription. OBJECTIVE: To examine associations between features of the first opioid prescription and high-risk opioid use in the 18 months following the first prescription. DESIGN: Retrospective cohort study using data from a large commercial insurance claims database for 2011-2014 to identify individuals with no recent use of opioids and follow them for 18 months after the first opioid prescription. PARTICIPANTS: Privately insured patients aged 18-64 and Medicare Advantage patients aged 65 or older who filled a first opioid prescription between 07/01/2011 and 06/30/2013. MAIN OUTCOMES AND MEASURES: High-risk opioid use was measured by having (1) opioid prescriptions overlapping for 7 days or more, (2) opioid and benzodiazepine prescriptions overlapping for 7 days or more, (3) three or more prescribers of opioids, and (4) a daily dosage exceeding 120 morphine milligram equivalents, in each of the six quarters following the first prescription. KEY RESULTS: All three features of the first prescription were strongly associated with high-risk use. For example, among privately insured patients, receiving a long- (vs. short-) acting first opioid was associated with a 16.9-percentage-point increase (95% CI, 14.3-19.5), a daily MME of 50 or more (vs. less than 30) was associated with a 12.5-percentage-point increase (95% CI, 12.1-12.9), and a supply exceeding 7 days (vs. 3 or fewer days) was associated with a 4.8-percentage-point increase (95% CI, 4.5-5.2), in the probability of having a daily dosage of 120 MMEs or more in the long term, compared to a sample mean of 4.2%. Results for the Medicare Advantage patients were similar. CONCLUSIONS: Long-acting formulation, high daily dosage, and longer duration of the first opioid prescription were each associated with increased high-risk use of opioids in the long term.

An Economic Evaluation of Coordinated Specialty Care (CSC) Services for First-Episode Psychosis in the U.S. Public Sector.

BACKGROUND: Schizophrenia spectrum disorders exert a large and disproportionate economic impact. Early intervention services may be able to alleviate the burden of schizophrenia spectrum disorders on diagnosed individuals, caregivers, and society at large. Economic analyses of observational studies have supported investments in specialized team-based care for early psychosis; however, questions remain regarding the economic viability of first-episode services in the fragmented U.S. healthcare system. The clinic for Specialized Treatment Early in Psychosis (STEP) was established in 2006, to explicitly model a nationally-relevant U.S. public-sector early intervention service. The purpose of this study was to conduct an economic evaluation of STEP, a Coordinated Specialty Care service (CSC) based in a U.S. State-funded community mental health center, relative to usual treatment (UT). METHODS: Eligible patients were within 5 years of psychosis onset and had no more than 12 weeks of lifetime antipsychotic exposure. Participants were randomized to STEP or UT. The annual per-patient cost of the STEP intervention per se was estimated assuming a steady-state caseload of 30 patients. A cost-offset analysis was conducted to estimate the net value of STEP from a third-party payer perspective. Participant healthcare service utilization was evaluated at 6 months and over the entire 12 months post randomization. Generalized linear model multivariable regressions were used to estimate the effect of STEP on healthcare costs over time, and generate predicted mean costs, which were combined with the per-patient cost of STEP. RESULTS: The annual per-patient cost of STEP was $1,984. STEP participants were significantly less likely to have any inpatient or ED visits; among individuals who did use such services in a given period, the associated costs were significantly lower for STEP participants at month 12. We did not observe a similar effect with regard to other healthcare services. The predicted average total costs were lower for STEP than UT, indicating a net benefit for STEP of $1,029 at month 6 and $2,991 at month 12; however, the differences were not statistically significant. CONCLUSIONS: Our findings are promising with regard to the value of STEP to third-party payers.

Hospitalization Risk and Potentially Inappropriate Medications among Medicare Home Health Nursing Patients.

BACKGROUND: Hospitalizations and potentially inappropriate medication (PIM) use are significant and costly issues among older home health patients, yet little is known about the prevalence of PIM use in home health or the relationship between PIM use and hospitalization risk in this population. OBJECTIVE: To describe the prevalence of PIM use and association with hospitalization among Medicare home health patients. DESIGN: Cross-sectional analysis using data from 132 home health agencies in the US. SUBJECTS: Medicare beneficiaries starting home health nursing services between 2013 and 2014 (n = 87,780). MAIN MEASURES: Prevalence of individual and aggregate PIM use at start of care, measured using the 2012 Beers criteria. Relative risk (RR) of 30-day hospitalization or re-hospitalization associated with individual and aggregate PIM use, compared to no PIM use. KEY RESULTS: In total, 30,168 (34.4%) patients were using at least one PIM, with 5969 (6.8%) taking at least two PIMs according to the Beers list. The most common types of PIMs were those affecting the brain or spinal cord, analgesics, and medications with anticholinergic properties. With the exception of nonsteroidal anti-inflammatory drugs (NSAIDs), PIM use across all classes was associated with elevated risk (10-33%) of hospitalization compared to non-use. Adjusting for demographic and clinical characteristics, patients using at least one PIM (excluding NSAIDs) had a 13% greater risk (RR = 1.13, 95% CI: 1.09, 1.17) of being hospitalized than patients using no PIMs, while patients using at least two PIMs had 21% greater risk (RR = 1.21, 95% CI: 1.12, 1.30). Similar associations were found between PIMs and re-hospitalization risk among patients referred to home health from a hospital. CONCLUSIONS: Given the high prevalence of PIM use and the association between PIMs and hospitalization risk, home health episodes represent opportunities to substantially reduce PIM use among older adults and prevent adverse outcomes. Efforts to address medication use during home health episodes, hospitalizations, and care transitions are justified.

Antidepressant Medication Management Among Older Patients Receiving Home Health Care.

OBJECTIVE: Antidepressant management for older patients receiving home health care (HHC) may occur through two pathways: nurse-physician collaboration (without patient visits to the physician) and physician management through office visits. This study examines the relative contribution of the two pathways and how they interplay. METHODS: Retrospective analysis was conducted using Medicare claims of 7,389 depressed patients aged 65 years or older who received HHC in 2006-2007 and who possessed antidepressants at the start of HHC. A change in antidepressant therapy (versus discontinuation or refill) was the main study outcome and could take the form of a change in dose, switch to a different antidepressant, or augmentation (addition of a new antidepressant). Logistic regressions were estimated to examine how use of home health nursing care, patient visits to physicians, and their interactions predict a change in antidepressant therapy. RESULTS: About 30% of patients experienced a change in antidepressants versus 51% who refilled and 18% who discontinued. Receipt of mental health specialty care was associated with a statistically significant, 10- to 20-percentage-point increase in the probability of antidepressant change; receipt of primary care was associated with a small and statistically significant increase in the probability of antidepressant change among patients with no mental health specialty care and above-average utilization of nursing care. Increased home health nursing care in absence of physician visits was not associated with increased antidepressant change. CONCLUSIONS: Active antidepressant management resulting in a change in medication occurred on a limited scale among older patients receiving HHC. Addressing knowledge and practice gaps in antidepressant management by primary care providers and home health nurses and improving nurse-physician collaboration will be promising areas for future interventions.

Optimal interval for hot water immersion tail-flick test in rats.

BACKGROUND: The hot water tail-flick test is widely used to measure the degree of nociception experienced by laboratory animals. This study was carried out to optimise interval times for the hot water immersion tail-flick tests in rats. METHOD: Ten different intervals from 10 s to 1 h were tested in 60 Sprague-Dawley male rats. At least eight rats were tested for each interval in three consecutive hot water tail-flick tests. Dixon's up-and-down method was also used to find the optimal intervals. The same rats were then divided into two groups. In Group N, naloxone was injected to reverse the prolonged latency times, whereas saline was used in the control Group S. RESULTS: Intervals of 10 s, 20 s, 30 min and 1 h did not significantly impact latencies, yielding similar results in three consecutive tests (p > 0.05). However, interval times of between 30 s and 20 min, inclusively, caused significantly prolonged latencies in the second and third tests (p < 0.001). Dixon's up-and-down method showed that 95% of the rats had prolonged latencies in hot water tail-flick tests at intervals longer than 32 s. Naloxone reversed prolonged latencies in Group N, whereas the latencies in Group S were further prolonged in 5 min interval tests. CONCLUSION: The optimal intervals for hot water tail-flick tests are either shorter than 20 s or longer than 20 min. The prolonged latencies after repetitive tests were attributable to an endocrine opioid.