Understanding the long-term impact of incident osteoporotic fractures on healthcare utilization and costs in Korean postmenopausal women.

This study provides long-term evidence that healthcare resource utilization and costs of care in women who experienced incident osteoporotic fractures remained higher than those in women without fractures over a span of 5 years. These findings emphasize the importance of early diagnostics and treatment for osteoporosis. PURPOSE: To evaluate healthcare resource utilization (HCRU) and costs of care over 5 years after the incident osteoporotic fractures (OF) in postmenopausal women. METHODS: We used data from the National Health Insurance Service databases 2011-2018. Women aged ≥ 50 years with incident OF (OF group) were matched to women without OF (non-OF group). HCRU (inpatient, outpatient, and emergency room [ER] visits) and costs of care (inpatient, outpatient, and ER visits) during the 5-year follow-up period were derived after propensity score matching (PSM). Additionally, we identified women with subsequent fractures within the first 2 years after the incident OF. RESULTS: After PSM, 47,238 OF and 134,813 non-OF women were identified. HCRU rates and costs of care were highest in the first year after OF and decreased substantially, but remained higher in the OF group during the entire follow-up period. The increase in cumulative HCRU rates over 5 years was highest in inpatient admissions with ER visits (138% higher in OF vs non-OF). The cumulative total costs over 5 years were 73% higher in the OF group than in the non-OF group, which was mostly driven by inpatient costs. Trends were similar for women with subsequent fractures, but they generally showed higher HCRU and costs than those in the total OF group. CONCLUSION: OF imposes a substantial and sustained economic burden on women, resulting in an approximately twofold increase in the cumulative cost over 5 years compared to women without fracture, which highlights the need for early diagnostics and treatment of osteoporosis.

Estimating the economic burden of osteoporotic fractures in a multinational study: a real-world data perspective.

Fracture-related costs vary by country. A standardized methodology and presentations were proposed to fairly assess the economic burden of osteoporotic fracture. Results indicated substantial costs of osteoporotic fractures for pharmacy, hospitalization, emergency care, and outpatient visits in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA. PURPOSE: The objective of this multinational, retrospective matched cohort study was to use a standardized methodology across different healthcare systems to estimate the burden of osteoporotic fracture (OF) in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA. METHODS: Within each country, healthcare resource utilization and direct costs of care were compared between patients with newly identified OF and a propensity score-matched cohort without OF during follow-up periods of up to 5 years. RESULTS: Across all five countries, the OF cohort had significantly higher rates and length of inpatient admissions compared with the non-OF cohort. In each country, the adjusted total costs of care ratio between OF and non-OF cohorts were significant. The adjusted cost ratios for pharmacy, inpatient care, emergency care, and outpatient visits were similarly higher in the OF cohort across countries. CONCLUSION: The current study demonstrates the substantial economic burden of OF across different countries when compared with matched non-OF patients. The findings would assist stakeholders and policymakers in developing appropriate health policies.

Antihistamine use and the risk of injurious falls or fracture in elderly patients: a systematic review and meta-analysis.

Despite their anticholinergic side effects, first-generation antihistamines are widely prescribed to elderly patients. A systematic review was conducted to synthesize real-world evidence. First-generation antihistamine use is considerably associated with an increased risk of injurious falls or fracture among the elderly. INTRODUCTION: First-generation antihistamines are considered potentially inappropriate for elderly patients owing to anticholinergic side effects. We aimed to determine whether elderly patients taking antihistamines are at increased risk of injurious falls or fracture. METHODS: We identified studies in MEDLINE, EMBASE, and several local databases through November 2016. Observational studies on the association between antihistamine use and the risk of injurious falls or fracture were selected. Quality of the studies and the level of evidence were assessed. The random-effects model was employed for meta-analysis, and heterogeneity was examined based on I-square and Cochrane's Q test. Subgroup analyses were performed when the heterogeneity among studies could not be explained. RESULTS: From 473 identified studies, five (three case-control studies, one cohort study, and one case-crossover study) were included in our analysis based on eligibility criteria. First-generation antihistamine use showed significantly increased risk of injurious falls or fracture (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.49-2.76, heterogeneity: p = 0.41, I2 = 0%). Studies including antihistamines of all generations or containing no generation information were dealing with falls during hospitalization. Among these studies, the association was statistically significant without heterogeneity (OR 2.89, 95% CI 1.71-4.89, heterogeneity: p = 0.42, I2 = 0%). Due to the small number of studies included and unadjusted results, meaningful interpretation based on subgroup analysis was limited. CONCLUSIONS: First-generation antihistamine use is considerably associated with increased risk of injurious falls or fracture among the elderly. Clinicians need to exercise caution when prescribing first-generation antihistamines to elderly patients.

A Large National Cohort Study of the Association between Bisphosphonates and Osteonecrosis of the Jaw in Patients with Osteoporosis: A Nested Case-control Study.

The purpose of this study was to examine the association between bisphosphonate exposure and osteonecrosis of the jaw (ONJ) in Korean patients with osteoporosis. A nested case-control study was performed using the claims database during 2002 to 2010 provided by the National Health Insurance Service. We identified a cohort of individuals with diagnosis of osteoporosis during 2002 to 2010. Cases and controls were identified during 2004 to 2010, and the date of potential cases of ONJ was defined as the index date. Bisphosphonate exposure was evaluated during 2 y prior to the index date. The association between bisphosphonate exposure and ONJ was tested by performing a conditional logistic regression analysis for matched data, and odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Subjects were classified as nonuser, recent user, past user, or continuous user, depending on the prescription of bisphosphonates in 2 periods (1 to 2 y and 0 to 1 y prior to the index date). Continuous users were defined as patients who were exposed to bisphosphonate in both periods. We also examined the impact of bisphosphonate medication compliance by measuring the cumulative duration of exposure (CDE) on the risk of ONJ. A total of 212 cases with ONJ and 2,120 controls matched by sex, age, income level, and insurance type were identified among 109,787 patients with osteoporosis out of 1,025,340 enrollees in the sample cohort. The odds of having ONJ after adjusting for patient comorbidities significantly increased in continuous users of bisphosphonates (OR, 3.9; 95% CI, 2.4 to 6.2) compared to nonusers. Increased odds of ONJ were observed as CDE increased. The adjusted OR in patients with 1.5 y < CDE ≤ 2 y prior to the index date was 7.8 (95% CI, 4.0 to 15.5) versus nonusers. Our study results support significantly increased occurrences of potential ONJ in patients with osteoporosis who were exposed to bisphosphonates compared to those without exposure.

Investigation of Werner protein as an early DNA damage response in actinic keratosis, Bowen disease and squamous cell carcinoma.

BACKGROUND: Werner protein (WRN) has DNA helicase activity and participates in recombination, replication and repair of DNA. Loss-of-function mutations in WRN gives rise to genetic instability and diseases such as premature ageing and cancer. Upregulation of WRN promotes proliferation and survival of cancer cells. AIM: To evaluate the expression pattern of WRN in closely related skin cancers and their correlation with age, sex and UV exposure. METHODS: Immunohistochemistry was used to investigate expression of WRN in formalin-fixed, paraffin wax-embedded tissue specimens of 9 squamous cell carcinoma (SCC), 15 actinic keratosis (AK), 11 Bowen disease (BD) and 11 normal-appearing peripheral tissue samples, obtained from patients during surgical resections. RESULTS: WRN expression was significantly increased in BD, AK and SCC compared with normal controls, with the mean WRN staining score being highest in BD, followed by AK and SCC. However, age, sex and sun exposure were not associated with WRN expression. CONCLUSIONS: To our knowledge, this is the first report to date investigating the expression of WRN in skin cancers. The overtly high expression of WRN in premalignant lesions and in in situ cancer, with relatively low WRN expression in SCC, may indicate that WRN contributes as a checkpoint for early DNA damage response in skin tumorigenesis.

Associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors in Korean obese women.

PURPOSE: It is important to identify a 'metabolically unhealthy obese' subset with higher cardiovascular risk among obese individuals. We investigated the associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors among Korean obese women. METHODS: This study was a sub-investigation of a double-blind randomized controlled trial that examined the additive effect of or list at on weight loss with sibutramine. A sample of 111 obese women were divided into T-carriers (CT/TT) or a homozygous CC group, according to the presence of the 825T allele at GNB3. These groups were compared to determine their associations with obesity-related metabolic risk factors, i.e., fasting plasma glucose, serum lipids, serum insulin/insulin resistance, and abdominal fat amounts. RESULTS: The allele frequencies of the GNB3 polymorphism were C allele = 59.5% and T allele = 40.5%. The T allele was found to be significantly associated with greater visceral fat and higher serum lipids, and these significances remained robust after adjusting for potential covariates. CONCLUSIONS: The GNB3 825T polymorphism is significantly associated with greater visceral fat and higher serum lipids in Korean obese women and it suggests that the GNB3 C825T is a determinant of obesity-related metabolic traits in this population.

Improving acne keloidalis nuchae with targeted ultraviolet B treatment: a prospective, randomized, split-scalp comparison study.

BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic scarring folliculitis with fibrotic papules on the occipital scalp. Its treatment is limited and unsatisfactory. OBJECTIVES: To determine whether targeted ultraviolet B (tUVB) phototherapy will (i) improve the clinical appearance of AKN and (ii) induce extracellular matrix remodelling in affected lesions. METHODS: Eleven patients with AKN were enrolled in a prospective, randomized, split-scalp comparison study. One randomly selected side of the scalp was treated with tUVB up to three times weekly for 8 weeks. After week 8, both sides were treated for eight additional weeks. Assessment included lesion counts in two 3 × 3-cm regions of interest (ROIs), one on each side of the scalp (ROI-1: tUVB weeks 0-16, ROI-2: tUVB weeks 9-16), patient self-assessment and analysis of MMP1, MMP9, TGFB1 and COL1A1 mRNA expression by quantitative reverse-transcription polymerase chain reaction. RESULTS: Before treatment, the mean lesion count was similar between tUVB-treated and untreated sides (14·8 vs. 15·0). After 8 weeks of tUVB, the mean lesion count decreased significantly to 9·4 ± 1·2 (P =  0·03), with no change on the untreated side. With continued treatment, the mean lesion count in ROI-1 decreased further to 7 ± 1·5 (P = 0·04) after 16 weeks of tUVB. CONCLUSIONS: tUVB significantly improved the clinical appearance of AKN, led to patient satisfaction and was well tolerated.

Effect of the G-protein ß3 subunit 825T allele on the change of body adiposity in obese female.

No clinical studies on the lipolytic effect of guanine nucleotide-binding protein ß3 subunit gene (GNB3) 825T polymorphism have been performed. This study was a subinvestigation of a 12-week randomized controlled trial (NCT01184560) for the additive effect of orlistat on sibutramine treatment. The analysis involved 101 obese females aged 18-49 years, genotyped at the GNB3 825 locus. To exclude any influence from potential confounders, we used an analysis of covariance model. After the intervention, fat mass proportion in total weight loss was significantly lower in subjects with a T allele than in those without a T allele (p = 0.034). GNB3 825T allele was associated with blunted fat mass reduction in obese females.

Cannabinoid receptor expression in HIV encephalitis and HIV-associated neuropathologic comorbidities.

AIMS: Cannabinoids have been proposed for treating various neurodegenerative disorders and as adjunct therapy for HIV+ patients with neurologic sequelae. The expression of cannabinoid receptors (CB1 and CB2) has been reported in neurodegenerative diseases and in simian immunodeficiency virus encephalitis, yet the receptor expression in the central nervous system of HIV+ individuals is not known. METHODS: An anti-CB1 antibody and two anti-CB2 antibodies were employed for immunohistochemistry in the cerebral cortex and white matter of HIV encephalitis (HIVE) and HIV-associated comorbidities, as well as control brains (HIV- and HIV+). RESULTS: By quantitative image analysis, we observed that CB1 was increased in HIVE brains and those with comorbidities, while CB2 was significantly increased in the white matter of HIVE. Morphologically, CB1 was present in neurones, and both CB1 and CB2 were present in meningeal macrophages and subpial glia in all brains. In HIVE, CB1 was found in white matter microglia and perivascular cells, while CB2 was increased in microglia, astrocytes and perivascular macrophages. Double immunofluorescence with cell-specific markers and immunoblots on primary cultured microglia and astrocytes substantiated the glial localization of the cannabinoid receptors and specificity of the antibodies. CONCLUSIONS: Our study indicates that cannabinoid receptor expression occurs in glia in HIVE brains, and this may have ramifications for the potential use of cannabinoid ligands in HIV-infected patients.

Expression of neuropeptides and their degrading enzymes in ACD.

BACKGROUND: Sensory neuropeptides such as neurokinin A or substance P modulate skin and immune cells the functions of neurokinin receptor activation during neurogenic inflammation. Zinc metalloproteases, such as neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), effectively control the bioavailability of these neuropeptide mediators, which are released from sensory nerves, immune and skin cells during cutaneous responses to endogenous or exogenous noxious stimuli. Recently, studies have suggested that neuropeptides are one of the major pathogenetic fact in many dermatoses, such as allergic contact dermatitis (ACD), atopic dermatitis and psoriasis. AIM: To investigate the expression of major neuropeptides, SP and its degrading enzymes such as NEP and ACE, in the lesions of ACD. METHODS: A skin biopsy was obtained from 10 patients with ACD. We analysed the expression of these molecules by immunohistochemical staining, confocal laser scanning microscopy, western blotting and reverse transcription PCR. RESULTS: There was a significant increase in expression of SP in keratinocytes from ACD lesions compared with those in control skin. There was also increased expression of ACE but not NEP in ACD. CONCLUSION: Neuropeptides and their degrading enzymes, particularly SP and ACE, have a significant role in the pathogenesis of ACD.

Intense pulsed light vs. pulsed-dye laser in the treatment of facial acne: a randomized split-face trial.

BACKGROUND: Various laser and light therapy have been increasingly used for the treatment of acne vulgaris. PATIENTS AND METHODS: Twenty patients with facial acne were treated using intense pulsed light (IPL) on one side of the face and pulsed dye laser (PDL) on the other to compare the efficacy and safety of IPL and PDL. Treatment was performed 4 times at 2-week intervals. Treatment effectiveness was determined using lesion counts, acne severity, patient subjective self-assessments of improvement, and histopathological examinations, which included immunohistochemical staining for transforming growth factor-beta (TGF-beta). RESULTS: Numbers of total acne lesions decreased following both treatments. For inflammatory lesions such as papules, pustules and nodules, IPL-treated sides showed an earlier and more profound improvement than PDL-treated sides. However, at 8 weeks after the 4th treatment, a rebound aggravation of acne was observed on IPL-treated sides. On the contrary, PDL produced gradual improvements during the treatment sessions and these improvements lasted 8 weeks after the 4th treatment. Non-inflammatory lesions as open and closed comedones also showed improvement following both treatments and PDL-treated sides showed better improvement as the study proceeded. Histopathological examinations showed amelioration in inflammatory reactions and an increase in TGF-beta expression after both treatments, which were more prominent for PDL-treated sides. CONCLUSION: Both PDL and IPL were found to treat acne effectively, but PDL showed a more sustained effect. TGF-beta might play a key role in the resolution of inflammatory acne lesions.

Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain.

AIMS: Microglia are involved in neurodegeneration, are prime targets for anti-inflammatory therapy and are potential biomarkers of disease progression. For example, positron emission tomography imaging employing radioligands for the mitochondrial translocator protein of 18 kDa (TSPO, formerly known as the peripheral benzodiazepine receptor) is being scrutinized to detect neuroinflammation in various diseases. TSPO is presumably present in activated microglia, but may be present in other neural cells. METHODS: We sought to elucidate the protein expression in normal human central nervous system, several neurological diseases (HIV encephalitis, Alzheimer's disease, multiple sclerosis and stroke) and simian immunodeficiency virus encephalitis by performing immunohistochemistry with two anti-TSPO antibodies. RESULTS: Although the overall parenchymal staining was minimal in normal brain, endothelial and smooth muscle cells, subpial glia, intravascular monocytes and ependymal cells were TSPO-positive. In disease states, elevated TSPO was present in parenchymal microglia, macrophages and some hypertrophic astrocytes, but the distribution of TSPO varied depending on the disease, disease stage and proximity to the lesion or relation to infection. Staining with the two antibodies correlated well in white matter, but one antibody also stained cortical neurones. Quantitative analysis demonstrated a significant increase in TSPO in the white matter of HIV encephalitis compared with brains without encephalitis. TSPO expression was also increased in simian immunodeficiency virus encephalitis. CONCLUSIONS: This report provides the first comprehensive immunohistochemical analysis of the expression of TSPO. The results are useful for informing the usage of positron emission tomography as an imaging modality and have an impact on the potential use of TSPO as an anti-inflammatory pharmacological target.

Vascular endothelial dysfunction tested by blunted response to endothelium-dependent vasodilation by salbutamol and its related factors in uncomplicated pre-menopausal obese women.

BACKGROUND: Vascular endothelial dysfunction (VED) plays a pivotal role in the pathogenesis of atherosclerosis and is associated with insulin resistance and visceral obesity. We examined the predicting factors of VED in uncomplicated premenopausal obese women using analysis of endothelium-dependent vasodilation by radial artery pulse wave obtained through applanation tonometry. METHODS: The subjects included a group of 33 obese women body mass index ((BMI) > or = 25) and another age-matched control group of 25 nonobese women (BMI: 18.5-22.9) of Asian origin. All uncomplicated premenopausal (20-45 y) obese women were sedentary (<1 h/week of physical activity). Anthropometric measurements were performed, and regional distributions of adipose tissue and metabolic variables were measured. Endothelial function was measured by pulse wave analysis after salbutamol administration, which reflects endothelium-mediated vasodilation, contributed partially by nitric oxide release from beta2-adrenergic stimulation. Radial artery wave forms were recorded and from a derived aortic wave forms augmentation index (AIx, defined as the pressure difference between the first and second peaks of the central arterial wave form, expressed as a percentage of the pulse pressure) was calculated. The subjects received sublingual nitroglycerine (NTG) (0.6 mg), followed by nebulized salbutamol (2.5 mg). RESULTS: AIx fell significantly after the administration of salbutamol, which causes endothelium-dependent vasodilatation. This value was significantly reduced in obese women compared with the controls (10.3+/-6.7 vs 17.2+/-6.8%, P=0.0003). NTG, which causes endothelium-independent vasodilatation, did not produce significant changes (P=0.917). As for our obese subjects, the visceral adipose tissue area was a significant predictor of VED independent of BMI, percent body fat, and other metabolic variables including high-sensitivity C-reactive protein (beta = -0.141, P=0.002, Adj-R(2)=0.41). CONCLUSION: Increased abdominal adiposity is a powerful independent predictor of VED in uncomplicated obese women. Further studies are warranted to determine the pathophysiological link between visceral adipose tissue and VED.

Anterior cingulotomy for refractory obsessive-compulsive disorder.

OBJECTIVE: This study was designed to prospectively investigate the efficacy and cognitive adverse effects of stereotactic bilateral anterior cingulotomy as a treatment for refractory obsessive-compulsive (OCD) patients for 12 months. METHOD: Patients were eligible if they had severe OCD and rigorous treatments had been unsuccessful. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Clinical Global Impression (CGI) and neuropsychological tests were used to assess the efficacy and cognitive changes of cingulotomy before and 12 months after operation. RESULTS: The mean improvement rate of the Y-BOCS scores achieved from baseline was 36.0%. Out of 14 patients six met responder criteria; 35% or higher improvement rate on Y-BOCS and CGI improvement of very much or much better at 12-month follow-up. There was no significant cognitive dysfunction after cingulotomy. CONCLUSION: Anterior cingulotomy shows few cognitive adverse effects, with about half of the OCD patients demonstrating significant symptomatic improvement.

Cytological observation of two environmental genic male-sterile lines of rice.

We report here two environmental genic male-sterilities (EGMS) in rice. These two EGMS rice lines, thermo-sensitive genic male-sterility (TGMS) and photoperiod-sensitive genic male-sterility (PGMS), are controlled by temperature and photoperiod, respectively, in determining their male-sterility. Male-sterility of the TGMS and PGMS was found to be induced when they were grown at 32 degrees C/26 degrees C (day/night) with 14 h daylight, while they were fertile at 26 degrees C/20 degrees C (day/night) with 10 h daylight in a growth chamber. We also examined their anther structures under a light microscope. The light microscopic observation revealed that the EGMS lines showed a complete pollen abortion at the sterile growth condition while they produced normal fertile pollens at the fertile growth condition.