Incidence and changes in treatment of acute exacerbation of idiopathic pulmonary fibrosis in Japan: A claims-based retrospective study.

BACKGROUND: Acute exacerbation is an essential prognostic factor in idiopathic pulmonary fibrosis (IPF) and is the leading cause of death in Japanese patients with IPF. Its epidemiology, treatment status, and effect on IPF progression have been insufficiently investigated. We examined the incidence of acute exacerbation and treatment status before and after the onset of acute exacerbation in Japanese patients with IPF to provide basic information for treatment strategies. METHODS: A Japanese claims database (April 2008-March 2019) from acute-care hospitals was analyzed. Incidence of acute exacerbation, time to the next event, and percentages of patients who received each treatment by the year before and after the onset of acute exacerbation were examined in patients diagnosed with IPF at least once. Acute exacerbation was defined according to the use of steroid pulse therapy. RESULTS: We identified 9961 patients with IPF and 2629 acute exacerbations (average age at the time of acute exacerbation: 74.8 years, percentage of men: 79%). The annual incidence of acute exacerbation was approximately 10% between 2010 and 2018. The time to the next acute exacerbation shortened with increasing number of these events. The percentage of patients receiving antifibrotic drugs remained constant (30%-40%) throughout the period. The percentages of patients receiving steroid therapy, immunosuppressive drugs, and oxygen therapy increased after the onset of acute exacerbation compared with before the onset. CONCLUSIONS: The annual incidence of acute exacerbation was approximately 10% in recent years. It is suggested that acute exacerbation worsens respiratory function in patients with IPF.

Current treatment status of patients with idiopathic pulmonary fibrosis in Japan based on a claims database analysis.

BACKGROUND: Treatment for idiopathic pulmonary fibrosis (IPF) has changed over the past decades. Understanding the actual status of IPF treatment and evaluating the consistency of the guidelines are important for improving the treatment strategy. However, the relevant information is insufficient in Japan. Therefore, this study investigated the treatment status and changes in the treatment of patients with IPF in Japan. METHODS: This retrospective claims-based study used a Japanese claims database that included data from acute care hospitals (April 2008-March 2019). Patients with at least one record of definitive IPF diagnosis were classified as patients with IPF. We determined the percentage of patients who received each treatment type by the year. RESULTS: We analyzed 9961 patients with IPF. The mean (standard deviation) age at first diagnosis was 74.4 (9.3) years, and 74.9% of the patients were men. The number of patients who did not take any drug treatment tended to decrease over the years. Nevertheless, approximately 30% of the patients did not take any drug treatment in recent years. The number of patients who received antifibrotic drugs increased over time, and it became the most popular treatment for ≥40% of the patients in and after 2017. Although steroid prescriptions tended to decrease over time, they were still administered to one-third of the patients with IPF who received drug treatment in and after 2017. CONCLUSIONS: Our findings suggest that changes in the IPF treatment reflect changes in guideline recommendations as well as the availability of treatment in clinical settings in Japan.

Diagnosis and treatment of influenza based on health insurance claims between the 2010-2011 and 2019-2020 influenza seasons in Japan.

Medical practices for influenza virus infection vary among countries. In Japan, treatment with anti-influenza drugs is recommended for patients diagnosed with influenza. This health claims database study provides quantitative information aimed at describing the actual medical practices, including diagnostic testing and medication use, for managing influenza in Japan. Most patients diagnosed with influenza underwent diagnostic tests and were prescribed anti-influenza drugs. Meanwhile, the majority of patients prescribed anti-influenza drugs had undergone diagnostic testing. However, an increase in the percentage of anti-influenza prescriptions without diagnostic testing was observed during the 2019-2020 influenza season, which may be associated with the COVID-19 pandemic.

Prevalence of idiopathic pulmonary fibrosis in Japan based on a claims database analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a cryptogenic chronic interstitial pneumonia with progressive fibrosis and a poor prognosis. A substantial number of epidemiological studies have been conducted in Europe and the United States (US). In contrast, in Japan, only one study reported the prevalence of IPF (10.0 per 100,000 population) using clinical data (2003-2007) from one prefecture; thus, the nationwide prevalence of IPF remains unknown. This study aimed to estimate the nationwide prevalence of IPF in Japan using a nationwide claims database. METHODS: We extracted data from a Japanese claims database provided by Medical Data Vision (MDV database, April 2008-March 2019) containing data from approximately 28 million patients from 385 acute-care hospitals. Patients with IPF (those diagnosed with IPF at least once) from April 2017 to March 2018 were identified in the MDV database. The number of patients in the MDV database was extrapolated nationwide using the fourth NDB Open Data (April 2017-March 2018), and the prevalence was estimated using demographic data as denominators. The prevalence in the US, considering the same definition of IPF, was also calculated and compared with that in Japan. RESULT: The number of patients with IPF in the MDV database was 4278. The estimated nationwide number of patients in Japan was estimated to be 34,040 (mean age: 73 years, percentage of men: 73%), and the prevalence was 27 per 100,000 population. In comparison with that in the US, the prevalence was similar in men and relatively lower in women until the age of 75-79 years, and it was notably lower in both sexes aged ≥ 80 years. CONCLUSIONS: We report the nationwide IPF prevalence in Japan using data from claims databases for the first time. The prevalence estimated in this study was higher than that reported in a previous study. The difference might be due to differences in study settings and definitions of IPF. Further research should be performed to determine the prevalence more accurately and compare it with those in other countries.

Effects of Lusutrombopag on Post-invasive Procedural Bleeding in Thrombocytopenic Patients with Chronic Liver Disease.

INTRODUCTION: Thrombocytopenia can increase the bleeding risk in patients with chronic liver disease (CLD) undergoing invasive procedures. Prophylactic platelet transfusion (PT) is often performed to increase platelet counts in patients with CLD undergoing invasive procedures to prevent bleeding. Lusutrombopag, a small-molecule thrombopoietin receptor agonist, is expected to be an alternative therapy to prophylactic PT. This study aimed to compare the effects between lusutrombopag and PT. METHODS: Data were obtained from a Japanese administrative database (April 2008-May 2019). Patients aged ≥ 18 years who underwent planned invasive procedures after the first CLD diagnosis and were observed for ≥ 30 days prior to invasive procedures were considered eligible. Patients who underwent planned invasive procedures with lusutrombopag prescription at 5-30 days before the procedure were categorized as the lusutrombopag group, whereas those who received PT at 1 day before and/or on the same day as the procedure, without lusutrombopag prescription, were classified as the PT group. Outcomes, including bleeding frequency during hospitalization and average medical costs (costs for prophylactic treatment and total costs between the day of the invasive procedure and 30 days after the invasive procedure), were compared between the groups after matching. RESULTS: Among 738,878 patients with CLD, 379 cases for each group were identified after matching. The incidence of bleeding events was lower in the lusutrombopag group than in the PT group (3.7% vs. 8.2%, p < 0.001). Average medical costs were lower in the lusutrombopag group than in the PT group ($6667 as of August 2021 vs. $7170, p = 0.011). CONCLUSION: Lusutrombopag is suggested to be effective as a prophylactic treatment for bleeding prevention in patients with CLD undergoing planned invasive procedures.

Confocal and multiphoton calcium imaging of the enteric nervous system in anesthetized mice.

Most imaging studies of the enteric nervous system (ENS) that regulates the function of the gastrointestinal tract are so far performed using preparations isolated from animals, thus hindering the understanding of the ENS function in vivo. Here we report a method for imaging the ENS cellular network activity in living mice using a new transgenic mouse line that co-expresses G-CaMP6 and mCherry in the ENS combined with the suction-mediated stabilization of intestinal movements. With confocal or two-photon imaging, our method can visualize spontaneous and pharmacologically-evoked ENS network activity in living animals at cellular and subcellular resolutions, demonstrating the potential usefulness for studies of the ENS function in health and disease.

Topological organization of CA3-to-CA1 excitation.

The CA1-projecting axons of CA3 pyramidal cells, called Schaffer collaterals, constitute one of the major information flow routes in the hippocampal formation. Recent anatomical studies have revealed the non-random structural connectivity between CA3 and CA1, but little is known regarding the functional connectivity (i.e. how CA3 network activity is functionally transmitted downstream to the CA1 network). Using functional multi-neuron calcium imaging of rat hippocampal slices, we monitored the spatiotemporal patterns of spontaneous CA3 and CA1 burst activity under pharmacological GABAergic blockade. We found that spatially clustered CA3 activity patterns were transformed into layered CA1 activity sequences. Specifically, synchronized bursts initiated from multiple hot spots in CA3 ensembles, and CA1 neurons located deeper in the pyramidal cell layer were recruited during earlier phases of the burst events. The order of these sequential activations was maintained across the bursts, but the sequence velocity varied depending on the inter-burst intervals. Thus, CA3 axons innervate CA1 neurons in a highly topographical fashion.

Heterogeneous effects of antiepileptic drugs in an in vitro epilepsy model--a functional multineuron calcium imaging study.

Epilepsy is a chronic brain disease characterised by recurrent seizures. Many studies of this disease have focused on local neuronal activity, such as local field potentials in the brain. In addition, several recent studies have elucidated the collective behavior of individual neurons in a neuronal network that emits epileptic activity. However, little is known about the effects of antiepileptic drugs on neuronal networks during seizure-like events (SLEs) at single-cell resolution. Using functional multineuron Ca(2+) imaging (fMCI), we monitored the activities of multiple neurons in the rat hippocampal CA1 region on treatment with the proconvulsant bicuculline under Mg(2+) -free conditions. Bicuculline induced recurrent synchronous Ca(2+) influx, and the events were correlated with SLEs. Other proconvulsants, such as 4-aminopyridine, pentetrazol, and pilocarpine, also induced synchronous Ca(2+) influx. We found that the antiepileptic drugs phenytoin, flupirtine, and ethosuximide, which have different mechanisms of action, exerted heterogeneous effects on bicuculline-induced synchronous Ca(2+) influx. Phenytoin and flupirtine significantly decreased the peak, the amount of Ca(2+) influx and the duration of synchronous events in parallel with the duration of SLEs, whereas they did not abolish the synchronous events themselves. Ethosuximide increased the duration of synchronous Ca(2+) influx and SLEs. Furthermore, the magnitude of the inhibitory effect of phenytoin on the peak synchronous Ca(2+) influx level differed according to the peak amplitude of the synchronous event in each individual cell. Evaluation of the collective behavior of individual neurons by fMCI seems to be a powerful tool for elucidating the profiles of antiepileptic drugs.

G protein-gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites.

BACKGROUND AND PURPOSE: Oxycodone and morphine are µ-opioid receptor agonists prescribed to control moderate-to-severe pain. Previous studies suggested that these opioids exhibit different analgesic profiles. We hypothesized that distinct mechanisms mediate the differential effects of these two opioids and investigated the role of G protein-gated inwardly rectifying potassium (K(IR)3 also known as GIRK) channels in their antinociceptive effects. EXPERIMENTAL APPROACH: Opioid-induced antinociceptive effects were assessed in mice, using the tail-flick test, by i.c.v. and intrathecal (i.t.) administration of morphine and oxycodone, alone and following inhibition of K(IR)3.1 channels with tertiapin-Q (30 pmol per mouse, i.c.v. and i.t.) and K(IR)3.1-specific siRNA. The antinociceptive effects of oxycodone and morphine were also examined after tertiapin-Q administration in the mouse femur bone cancer and neuropathic pain models. KEY RESULTS: The antinociceptive effects of oxycodone, after both i.c.v. and i.t. administrations, were markedly attenuated by K(IR)3.1 channel inhibition. In contrast, the antinociceptive effects of i.c.v. morphine were unaffected, whereas those induced by i.t. morphine were attenuated, by K(IR)3.1 channel inhibition. In the two chronic pain models, the antinociceptive effects of s.c. oxycodone, but not morphine, were inhibited by supraspinal administration of tertiapin-Q. CONCLUSION AND IMPLICATIONS: These results demonstrate that K(IR)3.1 channels play a primary role in the antinociceptive effects of oxycodone, but not those of morphine, at supraspinal sites and suggest that supraspinal K(IR)3.1 channels are responsible for the unique analgesic profile of oxycodone.