Changes of Nodular Size and Its Risk Factors in Iodine-Sufficient Area: a Retrospective Cohort Analysis of 7753 Thyroid Nodules

Background and Objectives@#Iodine is known to be an important factor in the occurrence of goiter, and South Korea is a region with sufficient iodine supplementation. In this regard, we checked the size change of thyroid nodules found by health check-up in Koreans and examined which risk factors influence the size change. @*Materials and Methods@#A total 7753 subjects who underwent thyroid sonography two or more times were included. We defined that there was a change in the size of the nodule when the difference in diameter identified in the last ultrasound was more than 3 mm. @*Results@#Thyroid nodules were decreased in 895 subjects (11.5%) and increased in 1041 subjects (13.5%). The rate of increased nodule was on an increasing trend according to the duration (annual percent change 2.6%, p＜0.001). In contrast, the rate of decreased nodule was unchanged. Predictive factors related to decrease of the nodule size were young age, male sex, larger initial nodule size and thyroiditis. Similarly, young age, larger initial nodule size and diffuse parenchymal abnormality were significant predictive factors for increased nodules. However, diffuse parenchymal abnormality was not a predictive factor when we analyzed only thyroid nodules larger than 1 cm. @*Conclusion@#In our study, 11.5-13.5% of benign thyroid nodules were increased or decreased during median 27 months of follow-up in iodine sufficient condition. Young age, larger initial size and diffuse parenchymal abnormality were common predictive factor affecting both the increase and decrease of thyroid nodules.

Meta-analysis of Intravitreal Injection of Anti-vascular Endothelial Growth Factors for Diabetic Macular Edema

PURPOSE: Intravitreal aflibercept, ranibizumab, bevacizumab, and dexamethasone are the most widely used drugs in the treatment of diabetic macular edema (DME). The aim of this study was to compare the efficacy and safety of anti-vascular endothelial growth factors and dexamethasone for the treatment of DME. METHODS: There were nine previous systematic reviews on this topic; we updated these high-quality reviews. Seven studies were added to two studies following a literature search. Efficacy outcomes were 1) average improvement in visual acuity, 2) proportion of patients who experienced an improvement in vision (an increase in best-corrected visual acuity (BCVA) of ≥ 15 in the Early Treatment Diabetic Retinopathy Study [ETDRS]), and 3) proportion of patients who experienced worsening vision (a decrease in BCVA of ≥ 15 in the ETDRS). Safety outcomes included systemic adverse events and ocular-related adverse events. RESULTS: The mean difference in the BCVA for ranibizumab versus bevacizumab treatment was 0.16 (95% confidence interval [CI]: −0.02, 0.34), and that for ranibizumab versus aflibercept was −0.08 (95% CI: −0.26, 0.10). The mean difference in the change of BCVA for aflibercept versus ranibizumab was −0.20 (95% CI: −0.40, −0.01), and that for aflibercept versus bevacizumab was −0.34 (95% CI: −0.53, −0.14). Other efficacy outcomes showed similar trends, and there was no significant difference between treatments. There was also no significant difference in both systemic and ocular adverse events rates between the treatments. CONCLUSIONS: In DME patients, the efficacy of aflibercept was found to be higher with respect to BCVA changes compared with ranibizumab or bevacizumab. However, there were no significant difference in terms of visual acuity improvement or visual acuity of more than 15 letters, nor in terms of anti-vascular endothelial growth factors (as a safety outcome).

Intravitreal Injection of Anti-vascular Endothelial Growth Factor in Age-related Macular Degeneration: a Systematic Review

PURPOSE: To compare the efficacy and safety of intravitreal injections of bevacizumab, ranibizumab, and aflibercept for the treatment of new patients with age-related macular degeneration (AMD). METHODS: We conducted an update of the most recent and high quality systematic reviews (Canadian Agency for Drug Technology in Health [CADTH] 2016). Three randomized clinical trials were added to 13 trials identified from the CADTH report. The efficacy outcomes were 1) average improvement in visual acuity, 2) proportion of patients who experienced an improvement in vision (an increase in best-corrected visual acuity (BCVA) of ≥ 15 on Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and 3) proportion of patients who experienced worsening of vision (decrease in BCVA of ≥ 15 ETDRS letters). In addition, safety outcomes included systemic adverse events and ocular-related adverse events. To analyze the outcomes of 16 randomized controlled trials, we conducted meta-analyses on the outcome measures. RESULTS: There was no significant difference in efficacy outcomes among anti-vascular endothelial growth factor (anti-VEGF) drugs. The mean difference in BCVA between ranibizumab and bevacizumab was 0.33 (95% confidence interval [CI]: −1.29, 1.95), and the odds ratio (OR) for a vision gain in the BCVA of ≥ 15 ETDRS letters for the ranibizumab versus aflibercept treatment was 1.02 (95% CI: 0.80, 1.30). There was also no significant difference in safety outcomes, except in terms of arterial thromboembolic events (ranibizumab vs. bevacizumab; OR: 2.15; 95% CI: 1.04, 4.41). CONCLUSIONS: The efficacy of anti-VEGF drugs for AMD patients was not significantly different. The safety of the drugs was also not significantly different, except in terms of arterial thromboembolic events.

Status of Usage of Anti-vascular Endothelial Growth Factor in Age-related Macular Degeneration

PURPOSE: To evaluate the current use of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) in patients with age-related macular degeneration (AMD). METHODS: We analyzed the number and medical costs of patients with AMD diagnosed by the National Health Insurance Corporation (2007–2016). We also analyzed the number and medical costs of such patients who received anti-VEGF treatment, and analyzed the frequency, period of use, and average medical cost of anti-VEGF use in AMD patients. Finally, we evaluated the use of anti-VEGF injections for new AMD patients. RESULTS: The number of patients with AMD was 236,158 in 2009 and 537,528 in 2016, which represented a 2.3-fold increase over 8 years. Of these, the number of patients undergoing anti-VEGF therapy increased steadily from 9,961 in 2009 to 35,762 in 2016. The mean number of cycles of ranibizumab or aflibercept per patient was 4.87 ± 3.37, and the mean interval between treatments was 2.89 months. On average, 6.2 injections were performed in the first year of diagnosis, and the frequency of use decreased with time, with an average of 1.2 cycles after 4 years of diagnosis. Among all AMD patients in 2016, the total medical cost of those treated with anti-VEGF was 76.9 billion won, and the average medical cost per person was 2,162,145 won. CONCLUSIONS: The use of two drugs, ranibizumab and aflibercept, as reflected in public health insurance claims, steadily increased over the study period. Notably, there was a tendency to substitute aflibercept for ranibizumab.

Use of Anti-vascular Endothelial Growth Factors for Diabetic Retnopathy: National Health Insurance Claims Data

PURPOSE: To evaluate the current use of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with diabetic retinopathy. METHODS: We determined the current number of diabetic retinopathy patients and their medical expenditure using National Health Insurance Service claims data (2007-2016). We also analyzed the medical costs of patients with diabetic retinopathy who received anti-VEGF treatment, including ranibizumab and aflibercept. We then evaluated aspects of the use of anti-VEGF injections, such as frequency and intervals, in newly diagnosed diabetic retinopathy patients who received anti-VEGF treatment, along with their medical costs. RESULTS: The number of patients with diabetic retinopathy was 397,956 in 2009 and 721,310 in 2016, a 1.8-fold increase over 8 years. Of these, the number of patients undergoing anti-VEGF therapy was 4,283 in 2015 and 4,270 in 2016. Of the diabetic retinopathy patients in 2016, the total medical cost of those treated with anti-VEGF was 1.5 billion won, and the average medical cost per person was 3,531,064 won. CONCLUSIONS: Based on the National Health Insurance claims data, the use of ranibizumab and aflibercept is increasing. The results of this study suggest that diabetic retinopathy will become an important public health issue.

Budget Impact Analysis of Anti-vascular Endothelial Growth Factor in Patients with Diabetic Macular Edema

PURPOSE: This study investigated the optimal strategy to minimize budgetary constraints on National Health Insurance (NHI) services, while maximizing the number of diabetic macular edema (DME) patients who receive anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: We estimated the potential budget impact of anti-VEGF treatments in DME patients based on perceived upcoming changes in reimbursement fees over the next 5 years (2018–2022). Four scenarios were evaluated: (1) current anti-VEGF treatment patterns, (2) the hypothetical reimbursement fee, (3) the introduction of a new molecule similar to current anti-VEGF treatments, and (4) the prescription of an off-label drug, bevacizumab. The number of patients, anti-VEGF treatments, and medical costs for each scenario were calculated using claims data from the Korean NHI system and anti-VEGF prescription data from a single hospital. RESULTS: The potential budget impact of anti-VEGF injections in patients with DME over the next 5 years was estimated to be about 97.7 billion and 106.2 billion KRW for scenarios 1 and 2, respectively. In scenario 3, in which a biosimilar product to anti- VEGF is used, the estimated budget of the NHI system would be approximately 98.4 billion KRW. If an off-label drug is reimbursed, roughly 79.5 billion KRW will be required for the NHI system's budget. CONCLUSIONS: If the revised fee structure for AMD patients is similarly applied to anti-VEGF injections for DME patients, the NHI fiscal requirements will increase disproportionately over the next 5 years compared to current reimbursement conditions. Given the growth of DME patients in toda's patient population, the use of a biosimilar or off-label drug is a financially viable alternative to reduce the overall burden on the NHI system.

Final Impact of Anti-Vascular Endothelial Growth Factor Treatment in Age-related Macular Degeneration

PURPOSE: To evaluate the effects of anti-vascular endothelial growth factor (VEGF) treatment on the healthcare-related finances of patients with age-related macular degeneration. METHODS: Changes in health care financing due to newly introduced benefit standards were predicted over the coming 5-year period (2018–2022). We also analyzed the financial impact of scenarios in which agents similar to anti-VEGF, such as the over-licensed drug bevacizumab, were introduced. For this purpose, the future number of patients receiving anti-VEGF treatments was estimated for various scenarios based on National Health Insurance Corporation claims data followed by an estimate of the financial burden. RESULTS: In the case of age-related macular degeneration, the current standard of care (14 times in a lifetime) was maintained in scenario 1. In 2018, the insurance budget for the coming 5-year period was estimated at approximately 440.3 billion won. The insurance cost for that period was estimated at approximately 560.1 billion won under the revised standard of December 2017 (scenario 2). For scenarios wherein, after 2020, similar treatments (scenario 3) and bevacizumab (scenario 4) were introduced, the estimated health insurance costs were 521 billion won and 419.7 billion won, respectively. CONCLUSIONS: Health insurance costs are projected to increase substantially due to the elimination of the 14 time pay standard; however, the actual budget will only moderately increase, due to new limitations of visual acuity ≤ 0.1 or in case of scarring/ atrophic lesions. Clinically similar agents and bevacizumab could be considered as alternatives to anti-VEGF treatment for age-related macular degeneration.

Urinary tract infections in infants under six months of age / 소아과

PURPOSE: Although suprapubic bladder aspiration(SBA) is the most reliable technique for identifying bacteriuria in young infant, no report has been published about the clinical manifestations of urinary tract infection(UTI) diagnosed by aspirated urine in Korea. This study was performed to examine clinical manifestations and related factors of UTI confirmed by a positive urine culture obtained by SBA in young infants. METHODS: We reviewed medical records of 159 infants younger than six months of age, who had been admitted for UTI to Korea University Ansan Hospital from January 2002 to June 2005. RESULTS: The male:female ratio was 5.1:1. The most common pathogen in urine culture was Escherichia coli(92.5 percent). Most of the gram-negative pathogens had high sensitivity to amikacin, or third generation cephalosporins and had low sensitivity to ampicillin, trimethoprim-sulfamethoxazole, or gentamicin. Hydronephrosis and vesicoureteral reflux(VUR) were present in 32.7 percent and 27.7 percent respectively. Renal cortical defects observed on DMSA scans were detected in 37.1 percent. Prolonged fever duration and hospital day, high erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels, hydronephrosis and VUR were related to the renal cortical defects(P<0.05). Rates of UTI-associated bacteremia and aseptic meningitis were 8.3 percent and 6.6 percent. CONCLUSION: Early differential diagnosis is very important in infants younger than 6 months of age with UTI because the clinical findings are non-specific and UTI-associated bacteremia and aseptic meningitis are concomitantly found. Because prolonged fever and higher ESR and CRP levels are risk factors of the renal cortical defects, radiologic evaluations and nephrologic follow-up were needed in identifying the predisposing congenital abnormalities and chronic renal scarring.

Serum Adiponectin Levels and Insulin Resistance in Obese Children / 소아과

PURPOSE: Adiponectin, adipose tissue-specific protein, has anti-inflammatory and anti-atherogenic properties. It has been found to have a negative correlation with obesity and to play a role in modulating glucose tolerance and insulin sensitivity. Serum adiponectin concentrations are decreased in adults with obesity and type 2 diabetes. We investigated the difference in adiponectin levels between obese and non-obese children, and evaluated the relationship of serum adiponectin with body mass index(BMI), serum fasting insulin, lipid profiles and homeostasis model assessment(HOMA) in children. METHODS: We measured serum adiponectin levels by radioimmunoassay in 113 children(82 obese children and 31 non-obese controls) from 8 to 15 years of age, and also checked BMI, fasting serum glucose, insulin and lipid profiles. Fasting and postprandial serum adiponectin concentrations were compared by oral glucose tolerance tests in 27 obese children. The correlations of adiponectin with BMI, insulin, low density lipoprotein(LDL)-cholesterol and HOMA were analyzed by Pearson's correlation. RESULTS: The serum adiponectin levels were significantly lower in the obese group(19.7 mg/mL) than in the non-obese group(27.5 mg/mL)(P< 0.01). Serum adiponectin concentrations were negatively correlated with BMI(r=-0.39, P< 0.01), serum insulin(r=-0.28, P< 0.01), LDL-C(r=-0.20, P< 0.01) and HOMA(r=-0.22, P< 0.01). At oral glucose tolerance tests in obese children, postprandial 2 hours adiponectin level(19.8 mg/mL) was decreased compared to fasting level(25.8 mg/mL)(P< 0.01). CONCLUSION: Serum adiponectin concentrations were inversely related to adiposity and insulin resistance in children. We suggest the serum adiponectin level could be used as an early marker of insulin resistance in obese children.

A Clinical Study of Aseptic Meningitis(1996-2002)

PURPOSE: This study was performed to investigate the epidemiologic features of the patients who were admitted and diagnosed as aseptic meningitis from 1996 to 2002 in Seoul Red Cross Hospital. In this study, we report the time of outbreaks, clinical manifestations, laboratory data and CSF examination results. METHODS: We reviewed the clinical records of 544 aseptic meningitis patients who were admitted to Seoul Red Cross Hospital from 1996 to 2002. We collected the data of the sex, age, clinical manifestations, peripheral blood and CSF examination results of the patients. RESULTS: The ratio of male to female was 2.3 : 1. The majority of the patients were between 1 and 5 years of age. 82.3% of the cases occurred from May to August with a peak incidence rate of 31.4% in June. The clinical manifestations were fever(92.6%), headache(88.9%), vomiting(87.9%), poor oral intake(54.9%), abdominal pain(35.8%) and neck stiffness(65.9%). On the blood examination, leukocytosis(WBC>10,000/mm3) was shown in 57.5%. On the CSF examination, WBC counts were less than 500/mm3 in 89% and protein levels were less than 45 mg/dL in 62.3% and glucose levels were more than 40 mg/dL in 97.1%. We did not isolate the causative viral agents. CONCLUSION: The clinical manifestations, and the blood and CSF profiles of the aseptic meningitis patients in this study showed no great differences compared to those in other aseptic meningitis studies.