Long-Term Efficacy and Safety of Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria and High Disease Burden: Real-World Data From Korea

Background@#Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. @*Methods@#This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled. @*Results@#At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. @*Conclusion@#These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

The Health-related Quality of Life for Children with a Mentally Ill Parent

Purpose@#This study is aimed to identify the health-related quality of life for children with a mentally ill parent. @*Methods@#The 13 participants were school-aged children whose parents were registered at the D Regional Mental Health Welfare Center. Data were collected using one-on-one interview with illustration cards and analyzed by content analysis. @*Results@#The participants were living a difficult life in anxiety amid a reversal of parent-child role, such as doing housework and taking care of their parents. The study revealed a love-hate family relationship that the participants wanted parental recognition and attention but they were frustrated by insufficient parental care and sibling conflict. Nevertheless, they only had each other themselves to trust and rely on. Their mixed health awareness and negative emotions were influenced by parents. Some of participants were exposed to dangerous environment such as domestic violence, and they need support system for help in difficult situations. Sometimes they felt happy by satisfying physiological, social, and self-esteem needs. They also showed a positive potential that they were matured more than peers through the experience of overcoming difficulties. @*Conclusion@#Not only were there not enough attention and support for the children with mentally ill people, but they were also exposed to an environment that threatens their physical or mental health. Therefore, to improve their health-related quality of life, there should be some integrated support of the community health system to cope with the challenges they face.

The Health-related Quality of Life for Children with a Mentally Ill Parent

Purpose@#This study is aimed to identify the health-related quality of life for children with a mentally ill parent. @*Methods@#The 13 participants were school-aged children whose parents were registered at the D Regional Mental Health Welfare Center. Data were collected using one-on-one interview with illustration cards and analyzed by content analysis. @*Results@#The participants were living a difficult life in anxiety amid a reversal of parent-child role, such as doing housework and taking care of their parents. The study revealed a love-hate family relationship that the participants wanted parental recognition and attention but they were frustrated by insufficient parental care and sibling conflict. Nevertheless, they only had each other themselves to trust and rely on. Their mixed health awareness and negative emotions were influenced by parents. Some of participants were exposed to dangerous environment such as domestic violence, and they need support system for help in difficult situations. Sometimes they felt happy by satisfying physiological, social, and self-esteem needs. They also showed a positive potential that they were matured more than peers through the experience of overcoming difficulties. @*Conclusion@#Not only were there not enough attention and support for the children with mentally ill people, but they were also exposed to an environment that threatens their physical or mental health. Therefore, to improve their health-related quality of life, there should be some integrated support of the community health system to cope with the challenges they face.

Real-time PCR quantification of 9 periodontal pathogens in saliva samples from periodontally healthy Korean young adults

PURPOSE: Few studies have examined periodontal pathogens from saliva samples in periodontally healthy young adults. The purposes of this study were to determine the prevalence of periodontopathic bacteria and to quantify periodontal pathogens in saliva samples using real-time polymerase chain reaction (PCR) assays in periodontally healthy Korean young adults under 35 years of age. METHODS: Nine major periodontal pathogens were analyzed by real-time PCR in saliva from 94 periodontally healthy young adults. Quantification of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Fusobacterium nucleatum, Campylobacter rectus, Peptostreptococcus anaerobius, and Eikenella corrodens was performed by DNA copy number measurement. RESULTS: F. nucleatum and E. corrodens were detected in all subjects; the numbers of positive samples were 87 (92.6%), 91 (96.8%), and 90 (95.7%) for P. gingivalis, P. anaerobius, and C. rectus, respectively. Other pathogens were also detected in periodontally healthy subjects. Analysis of DNA copy numbers revealed that the most abundant periodontal pathogen was F. nucleatum, which was significantly more prevalent than all other bacteria (P < 0.001), followed by P. anaerobius, P. gingivalis, E. corrodens, C. rectus, and T. denticola. There was no significant difference in the prevalence of each bacterium between men and women. The DNA copy number of total bacteria was significantly higher in men than in women. CONCLUSIONS: Major periodontal pathogens were prevalent in the saliva of periodontally healthy Korean young adults. Therefore, we suggest that the development of periodontal disease should not be overlooked in periodontally healthy young people, as it can arise due to periodontal pathogen imbalance and host susceptibility.

L1 Recombinant Proteins of HPV Tested for Antibody Forming Using Sera of HPV Quadrivalent Vaccine

Virus-like particles (VLPs) derived from human papillomavirus (HPV) L1 capsid proteins were used for HPV quadrivalent recombinant vaccine. The HPV quadrivalent vaccine is administrated in a 3-dose regimen of initial injection followed by subsequent doses at 2 and 6 months to prevent cervical cancer, vulvar, and vaginal cancers. The type 6, 11, 16, or 18 of HPV infection is associated with precancerous lesions and genital warts in adolescents and young women. The HPV vaccine is composed of viral L1 capsid proteins are produced in eukaryotic expression systems and purified in the form of VLPs. Four different the L1 protein of 3 different subtypes of HPV: HPV11, HPV16, and HPV18 were expressed in Escherichia coli divided into 2 fragments as N- and C-terminal of each protein in order to examine the efficacy of HPV vaccine. Vaccinated sera failed to recognize N-terminal L1 HPV type 16 and type 18 by western blot while they detected N-terminal L1 protein of HPV type 11. Moreover, the recombinant C-terminal L1 proteins of type 16 was non-specifically recognized by the secondary antibody conjugated with horseradish peroxidase. This expression and purification system may provide simple method to obtain robust recombinant L1 protein of HPV subtypes to improve biochemical analysis of antigens with immunized sera.

Dendritic Cell Dysfunction in Patients with End-stage Renal Disease

End-stage renal disease (ESRD) with immune disorder involves complex interactions between the innate and adaptive immune responses. ESRD is associated with various alterations in immune function such as a reduction in polymorphonuclear leukocyte bactericidal activity, a suppression of lymphocyte proliferative response to stimuli, and a malfunction of cell-mediated immunity at the molecular level. ESRD also increases patients' propensity for infections and malignancies as well as causing a diminished response to vaccination. Several factors influence the immunodeficiency in patients with ESRD, including uremic toxins, malnutrition, chronic inflammation, and the therapeutic dialysis modality. The alteration of T-cell function in ESRD has been considered to be a major factor underlying the impaired adaptive cellular immunity in these patients. However, cumulative evidence has suggested that the immune defect in ESRD can be caused by an Ag-presenting dendritic cell (DC) dysfunction in addition to a T-cell defect. It has been reported that ESRD has a deleterious effect on DCs both in terms of their number and function, although the precise mechanism by which DC function becomes altered in these patients is unclear. In this review, we discuss the effects of ESRD on the number and function of DCs and propose a possible molecular mechanism for DC dysfunction. We also address therapeutic approaches to improve immune function by optimally activating DCs in patients with ESRD.

IL-32-induced Inflammatory Cytokines Are Selectively Suppressed by α1-antitrypsin in Mouse Bone Marrow Cells

The induction of interleukin (IL)-32 in bone marrow (BM) inflammation is crucial in graft versus host disease (GvHD) that is a common side effect of allogeneic BM transplantation. Clinical trials on α-1 antitrypsin (AAT) in patients with GvHD are based on the preliminary human and mouse studies on AAT reducing the severity of GvHD. Proteinase 3 (PR3) is an IL-32-binding protein that was isolated from human urine. IL-32 primarily induces inflammatory cytokines in myeloid cells, probably due to PR3 expression on the membrane of the myeloid lineage cells. The inhibitory activity of AAT on serine proteinases may explain the anti-inflammatory effect of AAT on GvHD. However, the anti-inflammatory activity of AAT on BM cells remains unclear. Mouse BM cells were treated with IL-32γ and different inflammatory stimuli to investigate the anti-inflammatory activity of AAT. Recombinant AAT-Fc fusion protein inhibited IL-32γ-induced IL-6 expression in BM cells, but failed to suppress that induced by other stimuli. In addition, the binding of IL-32γ to PR3 was abrogated by AAT-Fc. The data suggest that the specific anti-inflammatory effect of AAT in mouse BM cells is due to the blocking of IL-32 binding to membrane PR3.

Species Specific Antiviral Activity of Porcine Interferon-α8 (IFNα8)

Interferons (IFNs) have been known as antiviral genes and they are classified by type 1, type 2, and type 3 IFN. The type 1 IFN consists of IFNα, IFNβ, IFNτ, and IFNω whereas the type 2 IFN consists of only IFNγ, which is a key cytokine driving T helper cell type 1 immunity. IFNλ belongs to the type 3 IFN, which is also known as IL-28 and IL-29 possessing antiviral activities. Type 1 IFN is produced by viral infection whereas type 2 IFN is induced by mitogenic or antigenic T-cell stimuli. The IFNτ of bovine was first discovered in an ungulate ruminant recognition hormone. IFNτ belongs to the type 1 IFN with the common feature of type 1 IFN such as antiviral activity. IFNs have been mostly studied for basic research and clinical usages therefore there was no effort to investigate IFNs in industrial animals. Here we cloned porcine IFNα8 from peripheral blood mononuclear cells of Korean domestic pig (Sus scrofa domestica). The newly cloned IFNα8 amino acid sequence from Korean domestic pig shares 98.4% identity with the known porcine IFNα8 in databank. The recombinant porcine IFNα8 showed potent antiviral activity and protected bovine Madin-Darby bovine kidney epithelial (MDBK) cells from the cytopathic effect of vesicular stomatitis virus, but it failed to protect human Wistar Institute Susan Hayflick (WISH) cells and canine Madin-Darby canine kidney epithelial-like (MDCK) cells. The present study demonstrates species specific antiviral activity of porcine IFNα8.

Conformance Analysis of Clinical Pathway Using Electronic Health Record Data / 대한의료정보학회지

OBJECTIVES: The objective of this study was to confirm the conformance rate of the actual usage of the clinical pathway (CP) using Electronic Health Record (EHR) log data in a tertiary general university hospital to improve the CP by reflecting real-world care processes. METHODS: We analyzed the application and matching rates of clinicians' orders with predefined CP order sets based on data from 164 inpatients who received appendectomies out of all patients who were hospitalized from August 2013 to June 2014. We collected EHR log data on patient information, medication orders, operation performed, diagnosis, transfer, and CP order sets. The data were statistically analyzed. RESULTS: The average value of the actual application rate of the prescribed CP order ranged from 0.75 to 0.89. The application rate decreased when the order date was factored in along with the order code and type. Among CP pre-operation, intra-operation, post-operation, routine, and discharge orders, orders pertaining to operations had higher application rates than other types of orders. Routine orders and discharge orders had lower application rates. CONCLUSIONS: This analysis of the application and matching rates of CP orders suggests that it is possible to improve these rates by updating the existing CP order sets for routine discharge orders to reflect data-driven evidence. This study shows that it is possible to improve the application and matching rates of the CP using EHR log data. However, further research should be performed to analyze the effects of these rates on care outcomes.

Development of the Ubiquitous Spaced Retrieval-Based Memory Advancement and Rehabilitation Training Program

OBJECTIVE: The Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program was developed by transforming the spaced retrieval-based memory training which consisted of 24 face-to-face sessions into a self-administered program with an iPAD app. The objective of this study was to evaluate the feasibility and efficacy of USMART in elderly subjects with mild cognitive impairment (MCI). METHODS: Feasibility was evaluated by checking the satisfaction of the participants with a 5-point Likert scale. The efficacy of the program on cognitive functions was evaluated by the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery before and after USMART. RESULTS: Among the 10 participants, 7 completed both pre- and post-USMART assessments. The overall satisfaction score was 8.0+/-1.0 out of 10. The mean Word List Memory Test (WLMT) scores significantly increased after USMART training after adjusting for age, educational levels, baseline Mini-Mental Status Examination scores, and the number of training sessions (pre-USMART, 16.0+/-4.1; post-USMART, 17.9+/-4.5; p=0.014, RM-ANOVA). The magnitude of the improvements in the WLMT scores significantly correlated with the number of training sessions during 4 weeks (r=0.793; p=0.033). CONCLUSION: USMART was effective in improving memory and was well tolerated by most participants with MCI, suggesting that it may be a convenient and cost-effective alternative for the cognitive rehabilitation of elderly subjects with cognitive impairments. Further studies with large numbers of participants are necessary to examine the relationship between the number of training sessions and the improvements in memory function.

Discovery of Outpatient Care Process of a Tertiary University Hospital Using Process Mining / 대한의료정보학회지

OBJECTIVES: There is a need for effective processes in healthcare clinics, especially in tertiary hospitals, that consist of a set of complex steps for outpatient care, in order to provide high quality care and reduce the time cost. This study aimed to discover the potential of a process mining technique to determine an outpatient care process that can be utilized for further improvements. METHODS: The outpatient event log was defined, and the log data for a month was extracted from the hospital information system of a tertiary university hospital. That data was used in process mining to discover an outpatient care process model, and then the machine-driven model was compared with a domain expert-driven process model in terms of the accuracy of the matching rate. RESULTS: From a total of 698,158 event logs, the most frequent pattern was found to be "Consultation registration > Consultation > Consultation scheduling > Payment > Outside-hospital prescription printing" (11.05% from a total cases). The matching rate between the expert-driven process model and the machine-driven model was found to be approximately 89.01%, and most of the processes occurred with relative accuracy in accordance with the expert-driven process model. CONCLUSIONS: Knowledge regarding the process that occurs most frequently in the pattern is expected to be useful for hospital resource assignments. Through this research, we confirmed that process mining techniques can be applied in the healthcare area, and through detailed and customized analysis in the future, it can be expected to be used to improve actual outpatient care processes.

Insulin Secretion and Incretin Hormone Concentration in Women with Previous Gestational Diabetes Mellitus

BACKGROUND: We examined the change in the levels of incretin hormone and effects of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) on insulin secretion in women with previous gestational diabetes (pGDM). METHODS: A 75-g oral glucose tolerance test (OGTT) was conducted on 34 women with pGDM. In addition, 11 women with normal glucose tolerance, matched for age, height and weight, were also tested. The insulin, GIP, GLP-1, and glucagon concentrations were measured, and their anthropometric and biochemical markers were also measured. RESULTS: Among 34 women with pGDM, 18 had normal glucose tolerance, 13 had impaired glucose tolerance (IGT) and 1 had diabetes. No significant differences were found in GLP-1 concentration between the pGDM and control group. However, a significantly high level of glucagon was present in the pGDM group at 30 minutes into the OGTT. The GIP concentration was elevated at 30 minutes and 60 minutes in the pGDM group. With the exception of the 30-minute timepoint, women with IGT had significantly high blood glucose from 0 to 120 minutes. However, there was no significant difference in insulin or GLP-1 concentration. The GIP level was significantly high from 0 to 90 minutes in patients diagnosed with IGT. CONCLUSION: GLP-1 secretion does not differ between pGDM patients and normal women. GIP was elevated, but that does not seem to induce in increase in insulin secretion. Therefore, we conclude that other factors such as heredity and environment play important roles in the development of type 2 diabetes.

Saphenous Mononeuropathy after Repetitive Compression on the Knee in a Ballerina: A Case Report

Saphenous mononeuropathy is an uncommon neuropathy in clinical condition, which may incur from various surgical procedures, direct trauma, or entrapment, and most frequently involves at the adductor canal, or Hunter's canal. A 17-year old female, who was majoring in ballet, visited our rehabilitation clinic for numbness in the medial aspect of the left lower leg for the previous 9 months, without weakness. The electrodiagnostic study revealed only a delayed small potential in the left saphenous nerve. MRI examination showed soft tissue swelling in the medial side of the left knee. Accordingly, we diagnosed the patient with saphenous mononeuropathy around the knee, without lumbar plexopathy or femoral neuropathy. We report a case of saphenous mononeuropathy which developed after repetitive compression on the medial side of the knee without any other iatrogenic injury, and include a review of the relevant literature.

The Burden of Aged Parents Caring for Adult Children with Disabilities

PURPOSE: This study was to describe the burden of aged parents caring for adult children with disabilities and related factors. METHODS: The subjects were 123 caregivers aged over 65 who were caring for 18-year-old or older children with disabilities. The research tool of this study was a structured questionnaire on family burden. Data were collected from June 3 to 25, 2010, and analyzed by Cronbach's alpha, mean, standard deviation, t-test, and ANOVA using SAS 9.2 program. RESULTS: The major findings of this study were as follows. Elderly parents caring for adult children with disabilities perceived a moderate level of burden. The burden from concern over their children's future was highest, and economic and physical burdens were higher when the parents were younger. Burden was significantly different according to parents' characteristics such as gender, perceived health status, disease, the costs of caring for disabled children, and children's characteristics such as disability rating, health status, and ADL. CONCLUSION: In order to reduce the burden of elderly parents caring for adult children with disabilities, we need to improve their health status and assess comprehensive policies.