Cost-utility analysis of endoscopic lumbar discectomy following a uniform clinical pathway in the Korean national health insurance system.

INTRODUCTION: Full-endoscopic lumbar discectomy (FELD) is a type of minimally invasive spinal surgery for lumbar disc herniation (LDH). Sufficient evidence exists to recommend FELD as an alternative to standard open microdiscectomy, and some patients prefer FELD due to its minimally invasive nature. However, in the Republic of Korea, the National Health Insurance System (NHIS) controls the reimbursement and use of supplies for FELD, but FELD is not currently reimbursed by the NHIS. Nonetheless, FELD has been performed upon patients' request, but providing FELD for patients' sake is inherently an unstable arrangement in the absence of a practical reimbursement system. The purpose of this study was to conduct a cost-utility analysis of FELD to suggest appropriate reimbursements. METHOD: This study was a subgroup analysis of prospectively collected data including 28 patients who underwent FELD. All patients were NHIS beneficiaries and followed a uniform clinical pathway. Quality-adjusted life years (QALYs) were assessed with a utility score using the EuroQol 5-Dimension (EQ-5D) instrument. The costs included direct medical costs incurred at the hospital for 2 years and the price of the electrode ($700), although it was not reimbursed. The costs and QALYs gained were used to calculate the cost per QALY gained. RESULT: Patients' mean age was 43 years and one-third (32%) were women. L4-5 was the most common surgical level (20/28, 71%) and extrusion was the most common type of LDH (14, 50%). Half of the patients (15, 54%) had jobs with an intermediate level of activity. The preoperative EQ-5D utility score was 0.48±0.19. Pain, disability, and the utility score significantly improved starting 1 month postoperatively. The average EQ-5D utility score during 2 years after FELD was estimated as 0.81 (95% CI: 0.78-0.85). For 2 years, the mean direct costs were $3,459 and the cost per QALY gained was $5,241. CONCLUSION: The cost-utility analysis showed a quite reasonable cost per QALY gained for FELD. A comprehensive range of surgical options should be provided to patients, for which a practical reimbursement system is a prerequisite.

Prokinetic Activity of Mulberry Fruit, Morus alba L.

The fruit of Morus alba L. (MAF) has been consumed as a food worldwide. MAF has also been widely used in traditional medicine for thousands of years in East Asia, and its diverse bioactivities have been reported in numerous publications. However, no prokinetic activity has been reported for MAF or its components. In the present study, therefore, we investigated the effects of MAF on gastrointestinal motor function by measuring the intestinal transit rate (ITR) of Evans blue in mice in vivo. The ITR values accelerated by MAF were significantly higher than those accelerated by cisapride or metoclopramide, suggesting that MAF has potential as a new prokinetic agent to replace cisapride and metoclopramide. We also investigated the effects of MAF on myogenic and neurogenic contractions in human intestinal smooth muscles by measuring spontaneous contractions of smooth muscle strips, smooth muscle contractions induced by neural stimulation, and migrating motor complexes from intestinal segments in the human ileum and sigmoid colon in situ. MAF increased both myogenic and neurogenic contractions to enhance ileal and colonic motility in the human intestine. Taken together, these results indicate that MAF enhanced intestinal motility by increasing both myogenic and neurogenic contractions, thereby accelerating the ITR.

Anti-obesity effects of red pepper (Capsicum annuum L.) leaf extract on 3T3-L1 preadipocytes and high fat diet-fed mice.

Patients with obesity mostly have metabolic syndrome and this can lead to multiple health problems. In the present study, we evaluated the anti-obesity effect of water-soluble red pepper (Capsicum annuum L.) leaf extract (PLE) on 3T3-L1 adipocytes and high-fat diet (HFD)-fed mice. The adipocyte lipid content was determined using Oil Red O staining, which revealed that 100 µg mL-1 PLE markedly reduced fat accumulation without affecting the cell viability. PLE exhibited high prebiotic activity scores by modulating probiotic strains, contributing to host health improvement. In vivo investigation in HFD-fed mice revealed that PLE supplementation significantly decreased the HFD-induced increases in the body weight, amount of white adipose tissue, and serum triglyceride, total cholesterol, leptin, and insulin levels. Consistent with its effects on reduced lipid droplet formation in the liver, PLE supplementation suppressed the expression of lipid synthesis-related proteins including SREBP-1, FAS, and PPAR-γ in the liver and increased that of PGC-1α, CPT1, and adiponectin in epididymal WAT. PLE treatment improved intestinal barrier function and inflammation and reduced harmful intestinal enzyme activities in the feces. Collectively, these results indicate that PLE inhibits fat accumulation in HFD-fed mice via the suppression of adipogenesis and lipogenesis, suggesting its potential in preventing obesity.

Direct medical costs after surgical or nonsurgical treatment for degenerative lumbar spinal disease: A nationwide matched cohort study with a 10-year follow-up.

OBJECTIVE: The demand for treating degenerative lumbar spinal disease has been increasing, leading to increased utilization of medical resources. Thus, we need to understand how the budget of insurance is currently used. The objective of the present study is to overview the utilization of the National Health Insurance Service (NHIS) by providing the direct insured cost between patients receiving surgery and patients receiving nonsurgical treatment for degenerative lumbar disease. METHODS: The NHIS-National Sample Cohort was utilized to select patients with lumbar disc herniation, spinal stenosis, spondylolisthesis or spondylolysis. A matched cohort study design was used to show direct medical costs of surgery (n = 2,698) and nonsurgical (n = 2,698) cohorts. Non-surgical treatment included medication, physiotherapy, injection, and chiropractic. The monthly costs of the surgery cohort and nonsurgical cohort were presented at initial treatment, posttreatment 1, 3, 6, 9, and 12 months and yearly thereafter for 10 years. RESULTS: The characteristics and matching factors were well-balanced between the matched cohorts. Overall, surgery cohort spent $50.84/patient/month, while the nonsurgical cohort spent $29.34/patient/month (p<0.01). Initially, surgery treatment led to more charge to NHIS ($2,762) than nonsurgical treatment ($180.4) (p<0.01). Compared with the non-surgical cohort, the surgery cohort charged $33/month more for the first 3 months, charged less at 12 months, and charged approximately the same over the course of 10 years. CONCLUSION: Surgical treatment initially led to more government reimbursement than nonsurgical treatment, but the charges during follow-up period were not different. The results of the present study should be interpreted in light of the costs of medical services, indirect costs, societal cost, quality of life and societal willingness to pay in each country. The monetary figures are implied to be actual economic costs but those in the reimbursement system instead reflect reimbursement charges from the government.

Biological activities of water-soluble polysaccharides from Opuntia humifusa stem in high-fat-diet-fed mice.

Water-soluble polysaccharide (WSP) of Opuntia humifusa stems was extracted and its biological activities in mice fed with a high-fat diet (HFD) were investigated. The mice were treated with oral doses of WSP for 4 weeks. Body weight, fat mass, serum lipid, and hormone profiles, gastrointestinal tract changes were evaluated. WSP treatment resulted in a decrease in fat mass and improvement of lipid and hormone profiles associated with HFD consumption. In addition, WSP improved the gastrointestinal health of the mice by increasing ghrelin-releasing cells and serotonin-positive cells and boosted immune functions by increasing the expression of CD4+ cells and nitric oxide synthase. Also, WSP treatment reduced gastrointestinal transit time and increased fecal moisture content. These findings suggest that a sufficient intake of WSP from O. humifusa can be beneficial in preventing disorders that are associated with the consumption of HFD including the preservation of gastrointestinal health. PRACTICAL APPLICATIONS: Opuntia humifusa is a traditional edible plant widely eaten in Asia for its high concentrations of vitamin C, polyphenols, and flavonoids. The research investigated the biological activity of WSP extracted from O. humifusa stems. The data obtained from this study sheds light on the use of plant-based polysaccharides in nutraceutical industries as potential functional food materials for the prevention of HFD-related disorders and improvement of gastrointestinal health. The results of this research could serve as a base for further research on this polysaccharide as a source of functional polysaccharides and promotes its usage on a large scale in functional food materials.

Eclipta prostrata promotes the induction of anagen, sustains the anagen phase through regulation of FGF-7 and FGF-5.

CONTEXT: Eclipta prostrata L. (Asteraceae) (EP) has been widely used for the treatment of skin disease in Asian traditional medicine. OBJECTIVE: This study investigates the potency of EP in promoting hair growth in vivo and in vitro. MATERIALS AND METHODS: C57BL/6N mice were divided into four groups (n = 4) as follows: control (topical treatment of normal saline), topical 3% minoxidil to the dorsal skin of mice for 14 days, and low (1 mg/day) and high (10 mg/day) doses of EP orally administered once a day for 14 days. Dorsal hairs of C57BL/6N mice were depilated to synchronize anagen induction. Hair growth activity was evaluated by gross and microscopic observations. Sections of dorsal skin were stained with haematoxylin and eosin. We also treated the various concentrations of EP (5, 10 and 50 µg/mL) for 24 h on the human dermal papilla cells (HDPs) and examined the effects of EP on the expression of FGF-7 and mTOR signalling. RESULTS: EP enhanced the induction of anagen in the dorsal skin of mice, characterized by the appearance of inner root sheath along with hair shaft, the emergence of hair shaft through the epidermis. EP increased the expression of FGF-7, while decreased the level of FGF-5 in C57/BL6 mice. EP also increased the expression of FGF-7, activated the mTOR signalling in HDPs. DISCUSSION AND CONCLUSIONS: These results suggest that EP has a potency to enhance the growth of hair follicle, promoting hair growth through regulation of FGF-7 and FGF-5.

Valerian extract alters functional brain connectivity: A randomized double-blind placebo-controlled trial.

Valerian root is the most commonly used herbal supplement for sedation and anxiolysis, but it is unknown whether it may affect functional brain connectivity. Our goal was to use electroencephalography (EEG) to investigate whether valerian root extract (VRE) affects resting-state connectivity changes and whether such changes are associated with clinical symptoms. This 4-week, double-blinded, randomized, placebo-controlled clinical trial was conducted with 64 nonclinical volunteers suffering psychological stress. The participants received VRE (100 mg) or a placebo thrice daily. We examined VRE's therapeutic effects on anxiety and stress-related psychological constructs. Functional brain connectivity changes were measured as EEG coherence in the alpha and theta frequency bands. The VRE and placebo groups both exhibited significant postintervention improvements on all clinical scales, but no significant between-group differences in these changes were noted. Compared with the placebo group, the VRE group exhibited significantly greater increases in frontal brain region alpha coherence across four electrode pairs, and these changes were significantly correlated with anxiolysis. The VRE group also exhibited significantly greater decreases in theta coherence across another four electrodes pairs. Our findings indicate that VRE alters functional brain connectivity in relation to anxiety. Further EEG studies are needed to confirm VRE's neurophysiological effects.

Citrus tachibana Leaves Ethanol Extract Alleviates Airway Inflammation by the Modulation of Th1/Th2 Imbalance via Inhibiting NF-κB Signaling and Histamine Secretion in a Mouse Model of Allergic Asthma.

Asthma is a chronic inflammatory disease of bronchial airway, which is characterized by chronic airway inflammation, airway edema, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration in the lungs. In this study, the therapeutic effect and the underlying mechanism of Citrus tachibana leaves ethanol extract (CTLE) in the ovalbumin (OVA)-induced allergic asthma and compound 48/80-induced anaphylaxis were investigated. Oral administration of CTLE inhibited OVA-induced asthmatic response by reducing airway inflammation, OVA-specific IgE and IgG1 levels, and increasing OVA-specific IgG2a levels. CTLE restored Th1/Th2 balance through an increase in Th2 cytokines tumor necrosis factor-α, interleukin (IL)-4, and IL-6 and decreases in Th1 cytokines interferon-γ and IL-12. Furthermore, CTLE inhibited the total level of NF-κB and the phosphorylation of IκB-α and NF-κB by OVA. In addition, CTLE dose-dependently inhibited compound 48/80-induced anaphylaxis via blocking histamine secretion from mast cells. The anti-inflammatory mechanism of CTLE may involve the modulation of Th1/Th2 imbalance via inhibiting the NF-κB signaling and histamine secretion. Taken together, we suggest that CTLE could be used as a therapeutic agent for patients with Th2-mediated or histamine-mediated allergic asthma.

Hypothermia Presenting in Wernicke Encephalopathy: A Case Report.

Wernicke encephalopathy (WE) is a neurologic disorder characterized by clinical symptoms, such as nystagmus, ataxia, and mental confusion. Hypothermia in patients with WE is a rare complication, and its pathogenic mechanism and therapy are yet to be ascertained. Herein, we presented a case of a 61-year-old man who was diagnosed with WE 3 months earlier. We investigated the cause of hypothermia (35.0℃) that occurred after an enema (bowel emptying). Brain magnetic resonance imaging revealed mammillary body and hypothalamus atrophy. In the autonomic function test, the sympathetic skin response (SSR) test did not evoke SSR latencies on both hands. In addition, abnormal orthostatic hypotension was observed. Laxative and stool softener medication were administered, and his diet was modified, which led to an improvement in constipation after 2 weeks. Moreover, there was no recurrence of hypothermic episode. This is the first reported case of late-onset hypothermia secondary to WE.

Effects of Distilled Cervi Pantotrichum Cornu and Rehmannia glutinosa Pharmacopuncture at GB21 (Jianjing) on Heart Rate Variability: A Randomized and Double-blind Clinical Trial.

BACKGROUND/PURPOSE: The purpose of this study was to use heart rate variability (HRV) to investigate the effects of distilled Cervi Pantotrichum Cornu pharmacopuncture and Rehmannia glutinosa pharmacopuncture on the autonomic nervous system. MATERIALS AND METHODS: Forty healthy male participants were divided into two groups: the participants of the C-group received distilled Cervi Pantotrichum Cornu pharmacopuncture and those of the R-group received Rehmannia glutinosa pharmacopuncture. The study design was a randomized, double-blind clinical trial. Each participant received one of the two solutions injected at GB21 (Jianjing). The changes in HRV were measured seven times using the QECG-3: LXC3203 system (LAXTHA Inc. Korea). Time-dependent changes in HRV for each group were analyzed using the paired t test (significance level: p < 0.05), and the difference in the HRV fluctuations between the two experimental groups was evaluated using the independent sample test (significance level: p < 0.05). RESULTS AND CONCLUSION: The results showed that Cervi Pantotrichum Cornu pharmacopuncture and Rehmannia glutinosa pharmacopuncture tended to activate the autonomic nervous system within the normal range. Cervi Pantotrichum Cornu pharmacopuncture tended to activate the sympathetic nervous system, whereas Rehmannia glutinosa pharmacopuncture tended to activate both the sympathetic and parasympathetic nervous systems.

Hominis Placenta facilitates hair re-growth by upregulating cellular proliferation and expression of fibroblast growth factor-7.

BACKGROUND: Hominis Placenta (HP) known as a restorative medicine in Traditional Chinese Medicine (TCM), has been widely applied in the clinics of Korea and China as an anti-aging agent to enhance the regeneration of tissue. This study was conducted to investigate whether topical treatment of HP promotes hair regrowth in the animal model. METHODS: The dorsal hairs of 8-week-old C57BL/6 mice were depilated to synchronize hair follicles to the anagen phase. HP was applied topically once a day for 15 days. Hair growth was evaluated visually and microscopically. The incorporation of bromodeoxyuridine (BrdU) and expression of proliferating cell nuclear antigen (PCNA), fibroblast growth factor-7 (FGF-7) in dorsal skin tissue was examined by immunohistochemical analysis. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of FGF-7. RESULTS: HP exhibited potent hair growth-promoting activity in C57BL/6 mice. Gross examination indicated that HP markedly increased hair regrowth as well as hair density and diameter. Histologic analysis showed that HP treatment enhanced the anagen induction of hair follicles. Immunohistochemical analysis revealed that BrdU incorporation and the expressions of PCNA were increased by treatment of HP. HP treatment significantly increased the expression of FGF-7, which plays pivotal roles to maintain anagen phase both protein and mRNA levels. CONCLUSIONS: Taken together, our results indicate that HP has a potent hair growth-promoting activity; therefore, it may be a good candidate for the treatment of alopecia.

Cornu cervi pantotrichum Pharmacopuncture Solution Facilitate Hair Growth in C57BL/6 Mice.

OBJECTIVES: Cornu cervi pantotrichum (CCP) has been widely used in Korean and China, as an anti-fatigue, anti-aging, and tonic agent to enhance the functions of the reproductive and the immune systems. Because CCP has various growth factors that play important roles in the development of hair follicles, we examined whether CCP pharmacopuncture solution (CCPPS) was capable of promoting hair growth in an animal model. METHODS: One day after hair depilation, CCPPS were topically applied to the dorsal skin of C57BL/6 mice once a day for 15 days. Hair growth activity was evaluated by using macro- and microscopic observations. Dorsal skin tissues were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor (FGF)-7 were examined by using immunohistochemical staining. A reverse transcription polymerase chain reaction (RT-PCR) analysis was also conducted to measure the messenger RNA (mRNA) expression of FGF-7. RESULTS: CCPPS induced more active hair growth than normal saline. Histologic analysis showed enlargement of the dermal papilla, elongation of the hair shaft, and expansion of hair thickness in CCPPS treated mice, indicating that CCPPS effectively induced the development of anagen. CCPPS treatment markedly increased the expressions of BrdU and PCNA in the hair follicles of C57BL/6 mice. In addition, CCPPS up regulated the expression of FGF-7, which plays an important role in the development of hair follicles. CONCLUSION: These results reveal that CCPPS facilitates hair re-growth by proliferation of hair follicular cells and up-regulation of FGF-7 and suggest that CCPPS can potentially be applied as an alternative treatment for patients with alopecia.

Effects of anti-inflammatory and Rehmanniae radix pharmacopuncture on atopic dermatitis in NC/Nga mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic and erythematous skin lesions. The purpose of this study was to investigate the suppressive effects of anti-inflammatory and Rehmanniae radix pharmacopuncture on the development of AD-like skin lesions in NC/Nga mice. The AD was induced on the mice's back skin by using biostir AD. The experimental groups were divided into three groups, PPI (anti-inflammatory pharmacopuncture), PPII (Rehmanniae radix pharmacopuncture, hydrodistillation extraction) and PPIII (Rehmanniae radix pharmacopuncture, MeOH extraction). All mice were treated using a 1-mL syringe to inject 0.1 mL of pharmacopuncture at right and left acupoints (BL13) on alternate days. In the control group, normal saline was used instead of pharmacopuncture. The following factors were investigated: (1) optical observations made with a handscope and clinical skin scores were evaluated; (2) tissue (general/immune) mast cells and CCR3(+) eosinophils, as well as vascular endothelial growth factor, fibroblast growth factor, and epidermal growth factor immunoreactive changes were evaluated; (3) CD4(+) and CD8(+) cells in the spleen were immunohistochemically examined; and, (4) the serum immunoglobulin (Ig)E level and lymphokines [interleukin (IL)-2, IL-4] were measured. In the PPI and the PPIII groups, the clinical skin score, total number of mast cells, CCR3(+) eosinophils immunoreaction, and total serum IgE, IL-2, and IL-4 levels were lower than the control group. The PPI and the PPIII groups also showed strong immunohistochemical reactions for vascular endothelial growth factor and fibroblast growth factor. The PPI group particularly showed a very strong immunohistochemical reaction for epidermal growth factor. All groups showed strong immune activity for CD8(+). The PPIII group showed strong immunity for both CD4(+) and CD8(+). From the above results, Rehmanniae radix pharmacopuncture (MeOH extraction) and anti-inflammatory pharmacopuncture exerted anti-allergic and anti-inflammatory effects, suggesting that they are promising agents for improving AD-related symptoms.

Effectiveness of electroacupuncture at Zusanli (ST36) on the immunohistochemical density of enteroendocrine cells related to gastrointestinal function.

The purpose of this study was to examine the effects of electroacupuncture at Zusanli on the immunohistochemical density of enteroendocrine cells related to gastrointestinal function. The authors investigated the histochemical changes of mucous substances and immunohistochemical density of gastrin, serotonin, calcitonin gene-related peptide (CGRP), insulin, and pancreatic polypeptide (PP) secreting cells in rats. Staining density of mucous substances and the enteroendocrine cells of the gastrointestinal tract was observed with histochemical and immunohistochemical methods. Stainless steel needles with a diameter of 0.25 mm were inserted into Zusanli (St36, 5mm below the head of the fibula under the knee joint, and 2mm lateral to the anterior tubercle of the tibia) and connected to an electrical stimulator. The electroacupuncture (EA) stimulation was delivered for 30 minutes at 10 mA, 2 Hz in EA stimulation (2EA group) or 4 Hz in EA stimulation (4EA group) in each experimental group. In 4EA stimulation at the Zusanli, staining density of Alcian blue-periodic acid-Schiff on mucous substances of the stomach body was stronger than those of the 2EA and control groups. Periodic acid-Schiff staining density of pyloric mucosa in the 4EA group was stronger than that of the 2EA and control groups. The immunohistochemical staining density of gastrin, serotonin, and CGRP-secreting cells of pylorus in the 2EA and 4EA groups was stronger than that of the control group. Immunohistochemical staining density of insulin and PP secreting cells of islets of the pancreas in the 2EA and 4EA groups was stronger than that of the control group. These results suggest that EA stimulus at St36 has the potential to influence gastric mucous substances and enteroendocrine cells (gastrin, serotonin, CGRP, insulin, and PP) that subsequently modulate digestive functions.

The effect of needle-embedding therapy and pharmacopuncture therapy on patients with urinary incontinence.

OBJECTIVES: This study was designed to evaluate the effect of traditional Korean medical therapy, consisting of needle-embedding therapy and pharmacopuncture therapy, on patients with urinary incontinence. METHODS: Twenty-nine patients with urinary incontinence underwent two sessions of traditional Korean medical therapy in a month. The pressure and the duration of pelvic muscle contraction were measured and compared. The primary endpoint of the study was improvement in the strength of pelvic floor muscle contraction. The paired t-test was used for the statistical analysis. RESULTS: Before treatment, a maximum pressure of 16.03 ± 6.28 mmHg and an average pressure of 9.62 ± 4.98 mmHg were measured, and the duration was 11.82 ± 12.08 seconds. After the first treatment, the pressures were 27.41 ± 10.46 mmHg (maximum) and 18.62 ± 9.72 mmHg (average), and the duration was 40.75 ± 60.02 seconds. After the second treatment, the pressures were 29 ± 14.86 mmHg (maximum) and 20.31 ± 11.51 mmHg (average), and the duration was 34.62 ± 42.02 seconds. Comparisons between before treatment and first treatment results and between before treatment and second treatment results showed statistically significant changes but the difference between the first treatment result and the second treatment result was not statistically significant. CONCLUSIONS: Patients receiving traditional Korean medical therapy showed improved pelvic muscle contraction ability after a single treatment. If strength of pelvic floor muscle contraction is improved, symptoms of urinary incontinence also get better. Traditional Korean medical therapy, with a focus on needle-embedding therapy and pharmacopuncture therapy, may be effective for treating urinary incontinence.

Inhibitory effect of Carthamus tinctorius L. seed extracts on bone resorption mediated by tyrosine kinase, COX-2 (cyclooxygenase) and PG (prostaglandin) E2.

Anti-bone resorption properties of the Korean herbal formulation, Honghwain (HHI; Carthamus tinctorius L. seed) was biochemically investigated. On processing bone metabolism, PGE2 accelerated production of IL-1beta in fetal mouse osteoblast and stimulated physiological activation substance, IL-1beta. The novel class of Src tyrosine kinase inhibitors, Herbimycin A (HERB) and HHI reduced COX-2 mRNA levels as well as PGE2 production induced by IL-1beta, TNF-alpha and IL-6. HHI inhibited in vitro and in vivo bone resorption by inhibition of phosphorylation of peptide substrates. HHI dose-dependently reduced the hypercalcemia induced in mice by IL-1beta and partly prevented bone loss and microarchitectural changes in young ovariectomized rats, showing that the protective effect on bone was exerted via the inhibition of bone resorption. These results indicate that the synergy between IL-beta, TNF-alpha, IL-6 on PGE2 production is due to an enhanced gene expression of COX-2 and that tyrosine kinase (s) are involved in the signal transduction of COX-2 in mouse calvarial osteoblasts. Thus, HHI as a possible Src family kinase inhibitor may be useful for the treatment of diseases associated with elevated bone loss.