Do rural and remote areas really have limited accessibility to health care? Geographic analysis of dialysis patients in Hiroshima, Japan

Introduction: For an equitable distribution of health resources, resource-allocation policies focus on rural and also remote areas, assuming that these areas are underserved. However, definitions of ‘rural’ and ‘remote’ vary, and are not necessarily synonymous with ‘underserved’. This Japanese study evaluated the association between the rurality/remoteness of the community in which a patient lives and his/her geographic accessibility to dialysis facilities. Methods: Based on 1867 communities (census blocks) in Hiroshima Prefecture, Japan, predictive powers of five community-level rural/remote parameters (population size, population density, elderly rate, agriculture rate, and distance to the nearest city) were evaluated to identify communities where dialysis patients had a longer commute time to dialysis facilities. The proportion of lowaccess communities was examined when those communities were merged to form larger geographic units (four-level stepwise merger). One- way driving times of dialysis patients were used as the access parameter of a community and were calculated using geographic information systems based on the addresses of all the 7374 patients certified by municipalities as having renal disability, and on the addresses and capacities of all 98 dialysis facilities in Hiroshima. Results: The average driving time was negatively correlated with population and population density, and positively correlated with elderly rate, agriculture rate, and distance to nearest city. When low-access was defined as >20, >30 & >40 min driving time, all rural/remote parameters showed better sensitivities (range 63.5-94.9%) than specificities (55.2-77.9%) to identify low-access communities, and positive predictive values were less than 50% for most parameters. When low-access was defined as >30 min driving time, the proportion of low-access communities substantially decreased when the geographic unit was expanded. In the administrative 'rural' area, the largest geographic unit, the percentage of low-access communities was 30%. Conclusions: In any definition of 'rural/remote', and in any definition of 'low-access', the rural/remote areas contain a substantial proportion of high-access communities. In addition, a substantial proportion of low-access communities was excluded from rural/remote areas. The accuracy of the term 'low-access' deteriorated when the geographic unit of analysis was expanded. In order to identify underserved areas precisely, it is necessary to set the geographic unit of analysis as small as possible and measure the geographic accessibility itself, rather than designate some areas as 'rural' or 'remote', based on conventional geographic/demographic/distance parameters

The impact of rural hospital closures on equity of commuting time for haemodialysis patients: simulation analysis using the capacity-distance model

Background: Frequent and long-term commuting is a requirement for dialysis patients. Accessibility thus affects their quality of lives. In this paper, a new model for accessibility measurement is proposed in which both geographic distance and facility capacity are taken into account. Simulation of closure of rural facilities and that of capacity transfer between urban and rural facilities are conducted to evaluate the impacts of these phenomena on equity of accessibility among dialysis patients. Methods: Post code information as of August 2011 of all the 7,374 patients certified by municipalities of Hiroshima prefecture as having first or third grade renal disability were collected. Information on post code and the maximum number of outpatients (capacity) of all the 98 dialysis facilities were also collected. Using geographic information systems, patient commuting times were calculated in two models: one that takes into account road distance (distance model), and the other that takes into account both the road distance and facility capacity (capacity-distance model). Simulations of closures of rural and urban facilities were then conducted. Results: The median commuting time among rural patients was more than twice as long as that among urban patients (15 versus 7 minutes, p<0.001). In the capacity-distance model 36.1% of patients commuted to the facilities which were different from the facilities in the distance model, creating a substantial gap of commuting time between the two models. In the simulation, when five rural public facilitiess were closed, Gini coefficient of commuting times among the patients increased by 16%, indicating a substantial worsening of equity, and the number of patients with commuting times longer than 90 minutes increased by 72 times. In contrast, closure of four urban public facilities with similar capacities did not affect these values. Conclusions: Closures of dialysis facilities in rural areas have a substantially larger impact on equity of commuting times among dialysis patients than closures of urban facilities. The accessibility simulations using the capacity-distance model will provide an analytic framework upon which rational resource distribution policies might be planned.The software used in this study was supplied by the Higher Education Grant Program of ESRI Japan Corp (Tokyo, Japan). Ministry of Education, Culture, Sports, Science and Technology (Tokyo, Japan) sponsored this research

Intrastriatal Memantine Infusion

Although the administration of dopamine precursor levodopa remains as the mainstay for the treatment of Parkinson’s disease, long-term exposure to levodopa often causes a disabling complication, referred to as levodopa-induced dyskinesias. Therefore, the development of new therapeutic interventions to dampen levodopa-induced dyskinesias and parkinsonian motor deficits is needed in the treatment of Parkinson’s disease. Intracerebral brain infusion has the merit of being able to specifically deliver any drug into any brain part. By using an intracerebral infusion system equipped with implantable, programmable, and refillable pumps, we show herein that continuous intrastriatal administration of memantine (MMT), which is a non-competitive N-methyl-D-aspartate receptor antagonist, attenuates levodopa-induced dyskinesias and parkinsonian signs in 6-hydroxydopamine-lesioned hemiparkinsonian mice that received daily levodopa treatment. Corroborating the general thought that overactivation of the striatal N-methyl-D-aspartate receptor function might generate levodopa-induced dyskinesias and parkinsonism, our results suggest that a continuous intrastriatal MMT infusion can be beneficial for the management of Parkinson’s disease with levodopa-induced dyskinesias. Our study also provides indications for the prototypic use of pharmacological deep-brain modulation through intracerebral infusion systems for treating medically intractable movement disorders

Video-based assessments of the hind limb stepping in a mouse model of hemi-parkinsonism

Unilateral injection of 6-hydroxydopamine (6-OHDA) is commonly used to generate a rodent model of Parkinson’s disease (PD). Although motor deficits of the lower extremities represent one of the major clinical symptoms in PD patients, validated tests for assessing motor impairments of the hind limb in 6-OHDA mice are currently unavailable. We here report the video-based assessments of the asymmetric use of hind limbs in 6-OHDA mice. A significantly decreased number of spontaneous hind limb stepping was observed in the contralateral-to-lesioned side, and was dose dependently reversed by levodopa, suggesting that it could be utilized for screening PD therapeutics

c-Abl Inhibition Exerts Antiparkinsonian Effects

Parkinson’s disease (PD) is caused by a progressive degeneration of nigral dopaminergic cells leading to striatal dopamine deficiency. From the perspective of antiparkinsonian drug mechanisms, pharmacologic treatment of PD can be divided into symptomatic and disease-modifying (neuroprotective) therapies. An increase in the level and activity of the Abelson non-receptor tyrosine kinase (c-Abl) has been identified in both human and mouse brains under PD conditions. In the last decade, it has been observed that the inhibition of c-Abl activity holds promise for protection against the degeneration of nigral dopaminergic cells in PD and thereby exerts antiparkinsonian effects. Accordingly, c-Abl inhibitors have been applied clinically as a disease-modifying therapeutic strategy for PD treatment. Moreover, in a series of studies, including that presented here, experimental evidence suggests that in a mouse model of parkinsonism induced by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, c-Abl inhibition exerts an immediate effect improving motor impairments by normalizing altered activity in striatal postsynaptic signaling pathways mediated by Cdk5 (cyclin-dependent kinase 5) and DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein 32 kDa). Based on this, we suggest that c-Abl inhibitors represent an ideal antiparkinsonian agent that has both disease-modifying and symptomatic effects. Future research is required to carefully evaluate the therapeutic efficacy and clinical challenges associated with applying c-Abl inhibitors to the treatment of PD

Anarchism and Recovery of Subject : Toward Normalization of A Utopia in Disorder

departmental bulletin pape

c-Abl Inhibition Exerts Symptomatic Antiparkinsonian Effects Through a Striatal Postsynaptic Mechanism

Parkinson’s disease (PD) is caused by a progressive degeneration of nigral dopaminergic cells leading to striatal dopamine deficiency. From the perspective of antiparkinsonian drug mechanisms, pharmacologic treatment of PD can be divided into symptomatic and disease-modifying (neuroprotective) therapies. An increase in the level and activity of the Abelson non-receptor tyrosine kinase (c-Abl) has been identified in both human and mouse brains under PD conditions. In the last decade, it has been observed that the inhibition of c-Abl activity holds promise for protection against the degeneration of nigral dopaminergic cells in PD and thereby exerts antiparkinsonian effects. Accordingly, c-Abl inhibitors have been applied clinically as a disease-modifying therapeutic strategy for PD treatment. Moreover, in a series of studies, including that presented here, experimental evidence suggests that in a mouse model of parkinsonism induced by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, c-Abl inhibition exerts an immediate effect improving motor impairments by normalizing altered activity in striatal postsynaptic signaling pathways mediated by Cdk5 (cyclin-dependent kinase 5) and DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein 32 kDa). Based on this, we suggest that c-Abl inhibitors represent an ideal antiparkinsonian agent that has both disease-modifying and symptomatic effects. Future research is required to carefully evaluate the therapeutic efficacy and clinical challenges associated with applying c-Abl inhibitors to the treatment of PD

Tespa1 is a novel inositol 1,4,5-trisphosphate receptor binding protein in T and B lymphocytes

AbstractTespa1 has been recently reported to be a critical molecule in T-cell development, however, the precise molecular mechanisms of Tespa1 remain elusive. Here, we demonstrate that Tespa1 shows amino-acid sequence homology to KRAS-induced actin-interacting protein (KRAP), an inositol 1,4,5-trisphosphate receptor (IP3R) binding protein, and that Tespa1 physically associates with IP3R in T and B lymphocytes. Two-consecutive phenylalanine residues (Phe185/Phe186) in Tespa1, which are conserved between Tespa1 and KRAP, are indispensable for the association between Tespa1 and IP3R. These findings suggest that Tespa1 plays critical roles in the immune system through the regulation of the IP3R

Partial acetalization of cyclic imides using an intramolecular oxetanyl group

Acetalization of only one carbonyl group of cyclic imides has been achieved in good yields by the Lewis acid catalyzed isomerization of easily accessible N-(3-oxetanylmethyl)-substituted imides.Embargo Period 12 month

Immunoglobulin Production by Peripheral Blood Mononuclear Cells in IgA Nephropathy Patients and their Relatives

Immunoglobulin production by peripheral blood mononuclear cells of 27 patients of IgA nephropathy and 11 relatives was determined. In comparison with 15 healthy controls, no significant difference could be observed in both IgA nephropathy patients and relatives of the group not stimulated with PWM, but in the group stimulated with PWM a significant elevation in the production of IgA, IgG and IgM was seen in IgA nephropathy patients, while in the relatives a significant elevation in production of IgA and IgG was observed. It is speculated that immune complexes mainly IgA are the chief cause of development and progression of IgA nephropathy and that IgG and IgM are also involved. In also relatives, the presence of immunological abnormalities similar to those of IgA nephropathy patients is suggested