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Timely access to innovative medical technologies driven by accelerated patient access pathways can substantially improve the health outcomes of patients who often have few therapeutic alternatives. We analyzed lead-times for the medical procedure reimbursement coverage process undertaken in South Korea from 2014 to 2017, which is considered one of the most important factors contributing to delays in patient access to new medical technologies.
This analysis was performed using the open datasets source of “Medical Procedure Expert Evaluation Committee (MPEEC)” meeting results and medical procedure coverage application information published on the Health Insurance Review and Assessment Service Web site.
From 2014 to 2017, 90 percent of all new coverage determinations took on average >250 days with almost 20 percent taking more than 2 years (>750 days), The average lead-time from the medical procedure coverage application to MPEEC meeting in 2015 was 435.0 ± 214.7 days (n = 26), which was significantly shorter than the average lead-time in 2014 (624.9 ± 290.3 days, n = 16) (p < .05). The average lead-time from application to official enforcement in 2015 was significantly shorter than that of 2014 (540.8 ± 217.4; n = 16 versus 734.1 ± 299.7 days; n = 26, respectively) (p < .05).
While this analysis showed a general trend of a reduction in the time taken to receive a positive coverage determination for a new medical technology, the average lead-time remains well over the government mandated 100 days. To continue this trend and further enhance the patient access pathway for medical procedure coverage determinations, some measures can be applied. In particular, the extended “One-Stop Service” program encompassing coverage determinations is one such recommendation that could be considered.
Failure at the proximal neck for endovascular aortic repair (EVAR) in abdominal aortic aneurysm (AAA) is more common in the presence of unfavorable proximal neck anatomy. In patients with hostile neck, EndoAnchors provide proximal fixation and reduces potential type I endoleak or endograft migration. However, the population size for AAA patients with hostile anatomic neck among Korean is unknown and cost-analysis with regard to EndoAnchors has not been established.
To figure out the population size of AAA patients with hostile neck anatomy, retrospective medical chart review was conducted from four major medical centers. Hostile proximal aortic neck was defined as any or all of neck length 28 mm, infrarenal neck angulation >60°, ≥50 percent of circumferential thrombus, ≥50 percent of calcified neck, and conical neck. Cost-analysis on EndoAnchor use for treatment purpose was conducted based on Korean National Health Insurance Claims dataset (HIRA-NIS 2015).
Two-hundred and ten patients’ anatomic data treated with EVAR were included; 130 (61.9 percent) patients met the criteria for a hostile aortic neck and 32 (15.2 percent) patients had multiple hostile anatomy parameters. Endograft migration was reported in four (1.9 percent) patients and intra or post-op type I endoleak was reported in 21 (10.0 percent) patients. Based on 1-year claims data, 1,607 patients were treated with EVAR in 2015 and the annual average medical costs for open repair were USD 16,151. Given the patients with type I endoleak or endograft migration needs open repair if not treated with EndoAnchors, the estimated annual costs for patients treated with EndoAnchor were USD 2,234,321 and those for patients without EndoAnchor were USD 2,595,508, therefore USD 361,187 can be saved annually.
The population size with hostile aortic neck in Korea was comparable with those in western countries. Economically, EndoAnchor is a cost-saving treatment for type I endoleak and migration after EVAR from Korean payer.
Given that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine.
Twenty-four symptomatically stable patients with schizophrenia were recruited from Seoul National University Hospital, 12 of which responded to first-line antipsychotic drugs (first-line AP group) and 12 under clozapine (clozapine group), along with 12 matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging and [18F]DOPA PET scans.
No significant difference was found in the total PANSS score between the patient groups. Voxel-based analysis showed a significant correlation between frontal FC to the associative striatum and the influx rate constant of [18F]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R2 = 0.019, p = 0.665; first-line AP group: R2 = 0.675, p < 0.001; clozapine group: R2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups.
The relationship between striatal dopamine synthesis capacity and frontostriatal FC is different between responders to first-line treatment and clozapine treatment in schizophrenia, indicating that a different pathophysiology could underlie schizophrenia in patients who respond to first-line treatments relative to those who do not.
Historically, patient access processes of new and innovative medical devices including in-vitro diagnostics are made in the sequence of regulatory approval, new Health Technology Assessment (nHTA) approval, reimbursement coverage and coding finally reaching the pricing approval stage in South Korea. Although the individual patient access process has its own distinct objective and perspective, there are still opportunities for the authorities or agencies in charge to streamline their processes by working together to promote earlier patient access of new and innovative medical devices to patients without impacting their own decision making.
This research examined and analyzed the current policies about: patient access processes with a holistic viewpoint, industry-wide survey about patient access practices; case studies of two innovative medical devices for patient access in South Korea and also proposed new or alternative programs which can contribute to patient access harmonization efforts with a holistic approach.
Historically, health authorities play defensive strategies by delaying the adoption of new and innovative medical devices and implementing certain periods (that is, 2 to 5 years) for a patient's out-of-pocket payment scheme. It is well illustrated with the statistic that only twenty-nine percent of new and innovative medical technologies which have successfully gone through the nHTA process were determined for reimbursement coverage in the past 7 years.
The survey by the medical device industry to determine the patient access lead-time of innovative medical devices with a holistic perspective indicated significantly delayed patient access even considerabley exceeding the legally required decision-making lead time. The in-depth case studies with two innovative devices indicated the disadvantageous patient access processes to the innovator in terms of both final approval timing and the price level.
The concurrent review process for reimbursement coverage decision making for medical procedures, medical devices and reimbursement coverage payment guidelines committed within the Health Insurance Review and Assessment Service shall be created. New programs to deal with uncertainty in reimbursement coverage decision making shall be considered such as coverage with evidence development, performance-based risk-sharing arrangement, multi-criteria decision analysis and economic evaluation.
We present a photometric study of the stars in ionizing star clusters embedded in several giant H II regions of M33 (CC93, IC 142, NGC 595, MA2, NGC 604 and NGC 588). Our photometry is based on the HST-WFPC2 images of these clusters. Color-magnitude diagrams and color-color diagrams of these clusters are obtained and are used for estimating the reddenings and ages of the clusters. The luminosity functions (LFs) and initial mass functions (IMFs) of the massive stars in these clusters are also derived. The slopes of the IMFs range from Γ = −0.5 to −2.1. Interestingly, it is found that the IMFs get steeper with increasing galactocentric distance and with decreasing [O/H] abundance.
To examine the hypothesis that the association between vitamin D deficiency and depressive symptoms is dependent upon total cholesterol level in a representative national sample of the South Korean population.
This was a population-based cross-sectional study.
The Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010–2012).
We included 7198 adults aged 20–88 years.
The incidence of depressive symptoms in individuals with vitamin D deficiency (serum 25-hydroxyvitamin D<20 ng/ml) was 1·54-fold (95 % CI 1·20, 1·98) greater than in individuals without vitamin D deficiency (serum 25-hydroxyvitamin D ≥20 ng/ml). The relationship was stronger in individuals with normal-to-borderline serum total cholesterol (serum total cholesterol<240 mg/dl; OR=1·60; 95 % CI 1·23, 2·08) and non-significant in individuals with high serum total cholesterol (OR=0·97; 95 % CI 0·52, 1·81) after adjustment for confounding variables (age, sex, BMI, alcohol consumption, smoking status, regular exercise, income level, education level, marital status, changes in body weight, perceived body shape, season of examination date and cholesterol profiles).
The association between vitamin D deficiency and depressive symptoms was weakened by high serum total cholesterol status. These findings suggest that both vitamin D and total cholesterol are important targets for the prevention and treatment of depression.
Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) study, we aimed to present the rates and clinical correlates of suicidal thoughts/acts in patients recruited from a total of 40 centres in 10 Asian countries/areas: China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand.
Data from 1122 patients with depressive disorders in the REAP-AD study were used. The ICD-10 was employed to diagnose depressive episodes and recurrent depressive disorder. The presence or absence of suicidal thoughts/acts and profile of other depressive symptoms was established using the National Institute for Health and Clinical Excellence guidelines for depression. Country/area differences in rates of suicidal thoughts/acts were evaluated with the χ2 test. In addition, depressive symptom profiles, other clinical characteristics, and patterns of psychotropic drug prescription in depressed patients with and without suicidal thoughts/acts were compared using analysis of covariance for continuous variables and logistic regression analysis for discrete variables to adjust the effects of covariates.
The rates of suicidal thoughts/acts in 10 countries/areas varied from 12.8% in Japan to 36.3% in China. Patients with suicidal thoughts/acts presented more persistent sadness (adjusted odds ratio [aOR]=2.64, p<0.001), loss of interest (aOR=2.33, p<0.001), fatigue (aOR=1.58, p<0.001), insomnia (aOR=1.74, p<0.001), poor concentration (aOR=1.88, p<0.001), low self-confidence (aOR=1.78, p<0.001), poor appetite (aOR=2.27, p<0.001), guilt/self-blame (aOR=3.03, p<0.001), and use of mood stabilisers (aOR=1.79, p<0.001) than those without suicidal thoughts/acts.
Suicidal thoughts/acts can indicate greater severity of depression, and are associated with a poorer response to antidepressants and increased burden of illness. Hence, suicidal thoughts/acts can provide a clinical index reflecting the clinical status of depressive disorders in Asians.
A total of forty weaned pigs ((Landrace×Yorkshire)×Duroc) were used to evaluate the effects of Lactobacillus acidophilus on inflammatory activity after lipopolysaccharide (LPS) challenge. Experimental treatments were as follows: (T1) control diet+saline challenge; (T2) control diet with 0·1 % L. acidophilus+saline challenge; (T3) control diet+LPS challenge; and (T4) control diet with 0·1 % L. acidophilus+LPS challenge. On d-14, piglets were challenged with saline (T1 and T2) or LPS (T3 and T4). Blood samples were obtained at 0, 2, 4, 6 and 12 h after being challenged and analysed for immune cell cytokine production and gene expression pattern. The L. acidophilus treatment increased the average daily weight gain (ADWG) and average daily feed intake (ADFI) compared with the control diet. With the control diet, the LPS challenge (T3) increased the number of immune cells and expression of TNF-α and IL-6 compared with the saline challenge (T1). Whereas with the saline challenge L. acidophilus treatment (T2) increased the number of leucocytes and CD4 compared with the control diet (T1), with the LPS challenge L. acidophilus treatment (T4) decreased the number of leucocytes, lymphocytes, CD4+ and CD8+ and expression of TNF-α and IL-6 compared with the control diet (T3). L. acidophilus treatment decreased the expression of TRL4 and NF-κB in peripheral blood mononuclear cells (PBMC) after LPS challenge, which leads to inhibition of TNF-α, IFN-γ, IL-6, IL-8 and IL1B1 and to induction of IL-4 and IL-10. We suggested that L. acidophilus improved ADWG and ADFI and protected against LPS-induced inflammatory responses by regulating TLR4 and NF-κB expression in porcine PBMC.
Cerebral white matter hyperintensities (WMH) are prevalent incident findings on brain MRI scans among elderly people and have been consistently implicated in cognitive dysfunction. However, differential roles of WMH by region in cognitive function are still unclear. The aim of this study was to ascertain the differential role of regional WMH in predicting progression from mild cognitive impairment (MCI) to different subtypes of dementia.
Participants were recruited from the Clinical Research Center for Dementia of South Korea (CREDOS) study. A total of 622 participants with MCI diagnoses at baseline and follow-up evaluations were included for the analysis. Initial MRI scans were rated for WMH on a visual rating scale developed for the CREDOS. Differential effects of regional WMH in predicting incident dementia were evaluated using the Cox proportional hazards model.
Of the 622 participants with MCI at baseline, 139 patients (22.3%) converted to all-cause dementia over a median of 14.3 (range 6.0–36.5) months. Severe periventricular WMH (PWMH) predicted incident all-cause dementia (Hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.43–3.43) and Alzheimer's disease (AD) (HR 1.86; 95% CI 1.12–3.07). Subcortical vascular dementia (SVD) was predicted by both PWMH (HR 16.14; 95% CI 1.97–132.06) and DWMH (HR 8.77; 95% CI 1.77–43.49) in more severe form (≥ 10 mm).
WMH differentially predict dementia by region and severity. Our findings suggest that PWMH may play an independent role in the pathogenesis of dementia, especially in AD.
The solid–water interface is ubiquitous in natural and synthetic systems as the primary site for chemical reactions under near-ambient conditions. Examples include the interactions of contaminants with mineral–water interfaces in natural environments, electrochemical reactions at the electrode-electrolyte interface relevant to energy storage (e.g., ion adsorption/electrical double layer formation, ion insertion), and oxidation of structural materials (e.g., rust). Yet many of these phenomena remain largely mysterious at a mechanistic level. The x-ray reflectivity technique, using highly penetrating hard x-rays, directly probes the solid–water interfaces through in situ studies. This approach has provided new insights into the molecular-scale structures and processes that occur at these “wet” interfaces. In this article, we review recent advances in the understanding of these systems, focusing specifically on the organization of interfacial “hydration layers” and the important role of adsorbed ions at charged solid–liquid interfaces.
The study's aim was to examine the association of alcohol consumption with verbal and visuospatial memory impairment in older people.
Participants were 1,572, aged ≥60 years, in the hospital-based registry of the Clinical Research Center for Dementia of South Korea (CREDOS). Moderate drinking was defined as no more than seven drinks per week and three drinks per day. Memory impairment was defined as performance with more than 1 standard deviation below the mean value on the Seoul Verbal Learning Test and Rey Complex Figure Test.
Those who consumed alcohol moderately, compared with abstainers, had a lower odds of verbal memory impairment (Odds Ratio [OR] = 0.64; 95% Confidence Interval [CI]: 0.46–0.87), adjusting for covariates. Visuospatial memory, however, was not significantly associated with alcohol consumption.
Moderate alcohol drinking is associated with a reduced likelihood of verbal memory impairment among older people attending memory clinics.
Nonlinear interactions between free-surface waves of the same wave speed and wind are studied by extending the linear resonant theory of Miles (J. Fluid Mech., vol. 3, 1957, pp. 185–204). A nonlinear interaction can occur when the steepness of a primary three-dimensional wave, which propagates obliquely to the wind direction, becomes of the order of the cube of the density ratio of air to water. If a secondary wave of smaller amplitude is also an oblique wave, the nonlinear critical-layer interaction between the primary and secondary fluctuations in air generates a difference mode whose wavenumbers are equal to the differences between the primary and secondary values. In addition, the nonlinear interaction in the critical layer between the primary and difference modes induces a parametric-growth effect on the secondary surface wave, if the frequency of the primary wave is higher than that of the secondary wave. The primary wave remains linear during this ‘ mode critical-layer interaction’ stage between two free-surface waves and a nonlinearly generated mode. The evolution of the secondary-wave amplitude is governed by an integro-differential equation and that of the difference mode is determined by an integral equation. Both inviscid and viscous numerical results show that the nonlinear growth rates become much larger than the linear growth rates. Effect of viscosity is shown to delay the onset of the nonlinear growth. The growth of the secondary and difference modes is more effectively enhanced when the signs of propagation angles of the primary and secondary waves are opposite than when they are equal. The mode interaction can occur when wave steepnesses are very small. The nonlinear interaction is entirely confined to a thin critical layer, and the perturbations outside the critical layer are governed by linear equations. It is shown that the initial nonlinear growth of a free-surface wave could be governed by a mode–mode interaction in air.
The oxidation behavior of Cu50Zr50 and Cu46Zr46Al8 glasses during continuous heating up to 1073 K has been investigated, with special emphasis on the oxidation resistance in the supercooled liquid (SCL) state. For Cu50Zr50, the oxide layer mostly consists of monoclinic ZrO2 (m-ZrO2), while for Cu46Zr46Al8, the oxide layer consists of two different layers: an outer layer consisting of tetragonal ZrO2 (t-ZrO2) + Al2O3 + metallic Cu (oxidation product from the SCL state of the glass matrix) and inner layer comprised of m-ZrO2 + metallic Cu islands (oxidation product from the crystallized matrix). Cu-enriched regions consisting of Cu51Zr14 (in Cu50Zr50) or AlCu2Zr + Cu70Zr15Al15 + Cu51Zr14 (in Cu46Zr46Al8) are present below the oxide layer. The present study shows that the addition of Al (8 at.%) in Cu50Zr50 results in a significant deterioration of the oxidation resistance in the SCL state since the solutionizing of Al in t-ZrO2 leads to a higher oxygen ion vacancy concentration, thus providing a higher activity of oxygen ions.
We present a rapid and sensitive surface acoustic wave (SAW) immunosensor that utilizes gold staining as a signal enhancement method. A sandwich immunoassay was performed on sensing area of the SAW sensor, which could specifically capture and detect cardiac markers (cardiac troponin I (cTnI), creatine kinase (CK)-MB, and myoglobin). The analytes in human serum were captured on gold nanoparticles (AuNPs) that were conjugated in advance with detection antibodies. Introduction of these complexes to the capture antibody-immobilized sensor surface resulted in a classic AuNP-based sandwich immunoassay format that has been used for signal amplification. In order to achieve further signal enhancement, a gold staining method was performed, which demonstrated that it is possible to obtain gold staining-mediated signal augmentation on a mass-sensitive device. The sensor response due to gold staining varied as a function of cardiac marker concentration.
New MR imaging techniques that limit artifacts in the abdomen have increased the role of MR imaging in detection and characterization of pancreatic disease. Advantages of imaging at 3T compared with 1.5T include thinner section acquisition (typically 2.5 mm versus 5 mm at 1.5T), higher matrix (typically 340 × 516 compared with 192 × 256), and high quality of T1-weighted three-dimensional (3D) gradient echo imaging . Standard sequences at 3T, which include breath-hold T1-weighted 3D gradient echo sequences, fat suppression techniques, and dynamic administration of gadolinium chelate, have resulted in image quality of the pancreas sufficient to detect and characterize focal pancreatic mass lesions smaller than 1 cm in diameter, and to evaluate diffuse pancreatic disease. MR cholangiopancreatography (MRCP) images acquired in a coronal oblique projection to delineate the pancreatic and bile duct is a useful addition. MRCP permits good demonstration of the biliary and pancreatic ducts to assess ductal obstruction, dilation, and abnormal duct pathways. The combination of parenchyma-imaging sequences and MRCP provides comprehensive information to evaluate the full range of pancreatic disease.
Despite numerous previous studies, relationships between watershed land use and adjacent streams and rivers at various scales in Korea remain unclear. This study investigated the relationships between land uses and the physical, chemical, and biological characteristics of 720 sites of streams and rivers across the country. The land uses at two spatial scales, including a 1-km buffer and the base watershed management region (BWMR), were computed in a geographical information system (GIS) with a digital land use/land cover map. Characteristics of land uses at two spatial scales were then correlated with the monitored multidimensional characteristics of the streams and rivers. The results of this study indicate that land use types have significant effects on stream and river characteristics. Specifically, most characteristics were negatively correlated with the proportions of urban, rice paddy, agricultural, and bare soil areas and positively correlated with the amount of forest. The site-scale and BWMR-scale analyses suggest that BWMR land use patterns were more strongly related to ecological integrity than they were to site land use patterns. Improving our understanding of land use effects will largely depend on relating the results of site-specific studies that use similar response techniques and measures to evaluate ecological integrity. In addition, our results clearly indicate that the characteristics of streams and rivers are closely linked and that land use types differentially affect those characteristics. Thus, effective restoration and management for ecological integrity of lotic system should consider the physical, chemical, and biological factors in combination.
We have studied infrared photoluminescence (PL) and x-ray diffraction (XRD) of 400 nm and 1500 nm thick InAs epilayers on GaAs, and 4 nm thick InAs on graded InGaAs layer with total thickness of 300 nm grown by molecular beam epitaxy. The PL peak positions of 400 nm, 1500 nm and 4 nm InAs epilayer measured at 10 K are blue-shifted from that of InAs bulk by 6.5, 4.5, and 6 meV, respectively, which can be largely explained by the residual strain in the epilayer. The residual strain caused by the lattice mismatch between InAs and GaAs or graded InGaAs/GaAs was observed from XRD measurements. While the PL peak position of 400 nm thick InAs layer is linearly shifted toward higher energy with increase in excitation intensity ranging from 10 to 140 mW, those of 4 nm InAs epilayer on InGaAs and 1500 nm InAs layer on GaAs is gradually blue-shifted and then, saturated above a power of 75 mW. These results suggest that adopting a graded InGaAs layer between InAs and GaAs can efficiently reduce the strain due to lattice mismatch in the structure of InAs/GaAs.
In the scribe lane, which is located at the frame neighboring two chips, most of the test patterns for monitoring electrical characteristics of memory device as well as various key patterns for photo process are formed. The pattern density of these regions is lower than that of the main chip area, and cause nitride erosion by dishing phenomena during HSS STI CMP process. Nitride erosion occurred in the scribe lane region, could the affect erosion properties of cell region in main chip area, results in within die remain nitride variation and marginal fail in device operation. In this work, in order to prevent these problems, pattern design in the scribe lane was modified so as not to occurs within die remain nitride variation. The effects of improvement in within die remain nitride variation were investigated by FIB-TEM analysis and its correlation with electrical properties were explained.