Clinical characteristics and drug utilisation patterns in patients with chronic cough: a retrospective cohort study using a Japanese claims database.

Background: Although unmet medical needs for better care of patients with chronic cough exist in Japan, epidemiological information about these patients and their treatments is very limited.

Objectives: To describe patient characteristics, underlying cough-related diseases and drug utilisation patterns in patients with chronic cough, and their changes over time.

Methods: This large retrospective claims database study enrolled subjects with chronic cough, identified either by a specific diagnostic cough code for chronic cough (Population 1) or by multiple cough-related diagnostic codes spanning > 8 weeks (Population 2).

Impact of refractory and unexplained chronic cough on disease burden: a qualitative study.

Background: Chronic cough lasting for > 8 weeks is a common medical condition that burdens patients. This study aimed to qualitatively describe knowledge, awareness, experiences, and subtypes of burdens (physical, social, psychological) among Japanese patients with refractory chronic cough (refractory to treatment of underlying relevant medical conditions) and unexplained chronic cough (symptoms of unexplained origin).

Methods: This non-interventional, cross-sectional study was conducted between February and March 2021 among patients (aged ≥ 20 years) with self-reported refractory or unexplained chronic cough.

Web-based survey to evaluate the prevalence of chronic and subacute cough and patient characteristics in Japan.

Background: Cough lasting 3-8 weeks and more than 8 weeks are defined as subacute/prolonged cough and chronic cough, respectively. Japanese chronic cough population has not been well studied. This study aimed to describe the prevalence and characteristics of chronic cough and subacute cough patients in Japan.

Disease burden and quality of life of patients with chronic cough in Japan: a population-based cross-sectional survey.

Background: Cough lasting 3-8 and >8 weeks are defined as subacute/prolonged cough and chronic cough (CC), respectively. Studies have revealed that CC negatively impact patients' quality of life (QoL). In Japan, there is limited data on the impact of CC on health-related quality of life (HRQoL), work productivity and activity impairment (WPAI) and healthcare resource utilisation (HRU) using validated instruments.

[Adherence to Oral Antihyperglycemic Agents (Dipeptidyl Peptidase-4 Inhibitors and Biguanides) and Its Associated Factors in Patients with Type 2 Diabetes].

To investigate medication adherence to oral antihyperglycemic agents and its associated factors in Japanese type 2 diabetic patients, a questionnaire survey was conducted in 983 adult patients receiving once-daily (QD) or twice-daily (BID) dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitor) or BID biguanides (BG) as monotherapy at 502 pharmacies in Japan. The percentage of patients with good adherence (the proportion of days in which patients took all pills as prescribed in the past 7 days ≥80%) was high (≥90%) in any dosing regimen with no significant difference among the groups. The following factors were identified as associating with good adherence: the longer duration of type 2 diabetes (≥1 year) (p=0.

Factors associated with reluctance to initiate or continue oral antihyperglycemic agent (OAHA) treatments in type 2 diabetes mellitus patients in Japan: An observational patient-reported study.

Background: Type 2 Diabetes Mellitus (T2DM) is undertreated in Japan. We sought to understand the potential factors associated with reluctance to initiate/continue oral antihyperglycemic agents (OAHA) treatment in Japan.

Methods: A two-phase study was conducted which included cognitive interviews in the first phase (N = 12) to ensure retrieval from memory of relevant information to respond to questions.

Association between sleep disturbance in Alzheimer's disease patients and burden on and health status of their caregivers.

Background: Sleep disturbance in Alzheimer's disease (AD) patients may have a negative impact not only on patients themselves but also on the physical and mental health of their caregivers. Detailed analysis of these issues is lacking.

Objective: This study investigated the association between sleep disturbance in AD patients and the burden on, and health status of, their caregivers in Japan.

Retrospective analysis of medical costs and resource utilization for severe hypoglycemic events in patients with type 2 diabetes in Japan.

Aims/introduction: The present study aimed to describe hospital utilization and examine actual medical costs for severe hypoglycemic events in patients with type 2 diabetes mellitus in Japan.

Materials And Methods: Medical resource utilization associated with severe hypoglycemia was evaluated using a receipt database of acute-care hospitals in Japan. Patients with type 2 diabetes treated with antihyperglycemic agents were included.

Incidence rate and patient characteristics of severe hypoglycemia in treated type 2 diabetes mellitus patients in Japan: Retrospective Diagnosis Procedure Combination database analysis.

Aims/introduction: To evaluate the incidence rate of and identify factors associated with severe hypoglycemic episodes in patients with treated type 2 diabetes mellitus.

Materials And Methods: Using Diagnosis Procedure Combination hospital-based medical database, we carried out a retrospective cohort study to assess the incidence rate of severe hypoglycemia in treated type 2 diabetes mellitus patients. We evaluated the associations between severe hypoglycemia and age, sex, complications, and current use of insulin or sulfonylurea (SU) in a nested case-control study.

Repulsive guidance molecule-a and demyelination: implications for multiple sclerosis.

Drug development for neurodegenerative and neuroinflammatory diseases such as multiple sclerosis and traumatic brain injury is challenging. One promising strategy is to target a molecule with multiple biological actions affecting divergent pathophysiological disease phases simultaneously since these diseases arise from multiple pathological phases. In recent years, we pursued this strategy with a focus on multiple sclerosis and spinal cord injury and found that repulsive guidance molecule-a (RGMa) inhibits regeneration of injured CNS axons following spinal cord injury.

Pain-related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain.

Background: The exact mechanism of knee osteoarthritis (OA)-associated pain is unclear, whereas mixed evidence of inflammatory pain and neuropathic pain has been noted. We aimed to investigate pain-related sensory innervation in a monoiodoacetate (MIA)-induced model of OA.

Methods: Sixty of seventy female Sprague Dawley rats of six week-old underwent intra-articular MIA and fluorogold (FG) retrograde neurotracer injection into their right (ipsilateral) knee, while their left knees were treated with FG in saline as a control (contralateral knee).

RGMa modulates T cell responses and is involved in autoimmune encephalomyelitis.

In multiple sclerosis, activated CD4(+) T cells initiate an immune response in the brain and spinal cord, resulting in demyelination, degeneration and progressive paralysis. Repulsive guidance molecule-a (RGMa) is an axon guidance molecule that has a role in the visual system and in neural tube closure. Our study shows that RGMa is expressed in bone marrow-derived dendritic cells (BMDCs) and that CD4(+) T cells express neogenin, a receptor for RGMa.

Th1 cells promote neurite outgrowth from cortical neurons via a mechanism dependent on semaphorins.

The roles of T lymphocytes in the central nervous system (CNS) are diverse; their roles in the injured CNS have been reported to be both detrimental and advantageous. Hence, an investigation of the effects of specific subsets of T cells on neurons may provide an insight into the interaction between the nervous system and the immune system. In the present study, we demonstrate that a specific subset of T lymphocytes enhanced neurite outgrowth in vitro.

Interferon-γ decreases chondroitin sulfate proteoglycan expression and enhances hindlimb function after spinal cord injury in mice.

Glial cells, including astrocytes and macrophages/microglia, are thought to modulate pathological states following spinal cord injury (SCI). In the present study, we evaluated the therapeutic effects of interferon-γ (IFN-γ), which is one of the cytokines regulating glial function, in a mouse contusive SCI model. We found that intraperitoneal injection of IFN-γ significantly facilitated locomotor improvement following SCI.

Chronic inflammatory demyelinating polyneuropathy sera inhibit axonal growth of mouse dorsal root ganglion neurons by activation of Rho-kinase.

Clinical course and prognosis are variable among patients with chronic inflammatory demyelinating polyneuropathy (CIDP), whereas the extent of axonal degeneration is the major prognostic factor. We studied the effects of sera from CIDP patients on axonal growth in cultured mouse dorsal root ganglion neurons. Compared with control sera, CIDP sera prominently suppressed axonal outgrowth of dorsal root ganglion neurons and shortened axonal length.

The therapeutic effects of Rho-ROCK inhibitors on CNS disorders.

Rho-kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase Rho. The Rho-ROCK pathway is involved in many aspects of neuronal functions including neurite outgrowth and retraction. The Rho-ROCK pathway becomes an attractive target for the development of drugs for treating central nervous system (CNS) disorders, since it has been recently revealed that this pathway is closely related to the pathogenesis of several CNS disorders such as spinal cord injuries, stroke, and Alzheimer's disease (AD).

Regulation of axonal elongation and pathfinding from the entorhinal cortex to the dentate gyrus in the hippocampus by the chemokine stromal cell-derived factor 1 alpha.

During the early developmental stage, a neural circuit is established between the entorhinal cortex (EC) and the hippocampal dentate gyrus (DG) via the perforant pathway. However, the manner in which the perforant fibers are navigated has mostly remained a mystery. Here, we analyzed the functional role of a chemokine, namely, stromal cell-derived factor 1alpha (SDF-1alpha), in the navigation of the perforant fibers.

Inhibition of branching and spine maturation by repulsive guidance molecule in cultured cortical neurons.

Repulsive guidance molecule (RGM) is a membrane-bound protein that was originally identified as an axon guidance molecule in the visual system. Functional studies in Xenopus and chick embryos revealed the roles of RGM in axon guidance and laminar patterning, while those in mouse embryos demonstrated its function in regulating cephalic neural tube closure. Moreover, RGM inhibition enhanced the growth of injured axons and promoted functional recovery after spinal cord injury in rats.

Peptides derived from repulsive guidance molecule act as antagonists.

Repulsive guidance molecule (RGM) is a membrane-bound protein that was originally identified as an axon guidance molecule in the visual system [T. Yamashita, B.K.

Rho-ROCK inhibitors for the treatment of CNS injury.

Injured axons in the adult central nervous system (CNS) exhibit almost no regeneration. Several myelin-associated proteins such as myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte-myelin glycoprotein (OMgp) have been identified as inhibitors of CNS axonal regeneration in the CNS. Recently, repulsive guidance molecule (RGM) was identified as a potential myelin-derived neurite outgrowth inhibitor in vitro and in vivo.

Myosin IIA is required for neurite outgrowth inhibition produced by repulsive guidance molecule.

Although myelin-associated neurite outgrowth inhibitors express their effects through RhoA/Rho-kinase, the downstream targets of Rho-kinase remain unknown. We examined the involvement of myosin II, which is one of the downstream targets of Rho-kinase, by using blebbistatin - a specific myosin II inhibitor - and small interfering RNA targeting two myosin II isoforms, namely, MIIA and MIIB. We found that neurite outgrowth inhibition by repulsive guidance molecule (RGMa) was mediated via myosin II, particularly MIIA, in cerebellar granule neurons.

Rho-ROCK inhibitors as emerging strategies to promote nerve regeneration.

Several myelin-associated proteins in the central nervous system (CNS) have been identified as inhibitors of axonal regeneration following the injury of the adult vertebrate CNS. Among these inhibitors, myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte-myelin glycoprotein (OMgp) are well characterized. Recently, the repulsive guidance molecule (RGM) was included as a potent myelin-derived neurite outgrowth inhibitor in vitro and in vivo.

Repulsion of cerebellar granule neurons by chondroitin sulfate proteoglycans is mediated by MAPK pathway.

Inhibitory molecules associated with myelin and glial scar formation inhibit axon regeneration after an injury to the central nervous system (CNS). Chondroitin sulfate proteoglycans (CSPGs) that are expressed in the scar contribute to the non-permissive properties of the CNS environment. Here, we employed a spot substrate assay and demonstrated that CSPGs have a repulsive effect on cell bodies as well as neurites of the postnatal cerebellar granule neurons (CGNs) in vitro.

BMP inhibits neurite growth by a mechanism dependent on LIM-kinase.

Bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor-beta superfamily. BMPs regulate several crucial aspects of embryonic development and organogenesis. Here, we demonstrate that BMP-2 inhibits the neurite outgrowth of postnatal cerebellar neurons in vitro.