Objective: We conducted a systematic review and meta-analysis to analyze the effects of cardiac rehabilitation (CR) on post-discharge prognoses of patients with acute myocardial infarction (AMI). Methods: A literature search was conducted through four international medical and two Korean databases. Primary outcomes for the effectiveness of CR included all-cause mortality, cardiovascular mortality, recurrence, revascularization, major adverse cardiovascular event, major adverse cardiocerebrovascular event, and readmission. We summarized and analyzed results of studies about CR for AMI, including not only randomized controlled trials (RCTs) but also non-RCTs. We calculated the effect size separately by the study type. Results: Fourteen articles were finally selected. Of these, two articles were RCTs, while 12 were non-RCTs. In RCTs, the overall mortality rate was lower in the group that participated in CR than that in the conventional care group by 28% (relative risk=0.72; 95% confidence interval, 0.34–1.57). Among non-RCTs, CR participation significantly decreased the overall risk of mortality. Moreover, the rates of recurrence and major adverse cardiovascular events were lower in the group that participated in CR compared to those in the non-CR group. Conclusion The meta-analysis shows that CR reduces the risk of re-hospitalization and all-cause mortality after AMI, compared to no participation in CR. This outcome was seen in RCTs as well as in non-RCTs. More studies are necessary for concrete conclusions about the beneficial effects of CR after AMI in various settings.

Background: Advanced cancers are associated with more severe symptoms and greater impairment. Although most patients with metastatic cancer would benefit from rehabilitation, few patients receive appropriate rehabilitation therapy. We explored the use of rehabilitation therapy by cancer patients. Our data represented the entire population of Korea. The analyses were performed according to cancer type and stage. Methods: We extracted rehabilitation utilization data of patients newly diagnosed with cancer in the period of 2011–2015 from the Korea Central Cancer Registry, which is linked to the claims database of the National Health Insurance Service (n = 958,928). Results: The utilisation rate increased during the study period, from 6.0% (11,504) of 192,835 newly diagnosed patients in 2011 to 6.8% (12,455) of 183,084 newly diagnosed patients in 2015. Patients with central nervous system (28.4%) and bone (27.8%) cancer were most likely to undergo physical rehabilitation. The rehabilitation rate was higher in patients with metastatic than localised or regional cancer (8.7% vs. 5.3% vs. 5.5%). Conclusion This claims-based study revealed that rehabilitation therapy for cancer patients is underutilised in Korea. Although patients with metastasis underwent more intensive rehabilitation than patients with early stage cancer, those without brain and bone tumours (the treatment of which is covered by insurance) were less likely to use rehabilitation services. Further efforts to improve the use of rehabilitation would improve the outcomes of cancer patients.

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).
Bevacizumab ; Dexamethasone ; Diabetic Retinopathy ; Endothelial Growth Factors ; Humans ; Intravitreal Injections ; Macular Edema ; Ranibizumab ; Visual Acuity

BACKGROUND: The objective of this study was to establish the efficacy and safety of procalcitonin (PCT)-guided antibiotic discontinuation in critically ill patients with sepsis in a country with a high prevalence of antimicrobial resistance and a national health insurance system. METHODS: In a multi-center randomized controlled trial, patients were randomly assigned to a PCT group (stopping antibiotics based on a predefined cut-off range of PCT) or a control group. The primary end-point was antibiotic duration. We also performed a cost-minimization analysis of PCT-guided antibiotic discontinuation. RESULTS: The two groups (23 in the PCT group and 29 in the control group) had similar demographic and clinical characteristics except for need for renal replacement therapy on ICU admission (46% vs. 14%; P = 0.010). In the per-protocol analysis, the median duration of antibiotic treatment for sepsis was 4 days shorter in the PCT group than the control group (8 days; interquartile range [IQR], 6–10 days vs. 14 days; IQR, 12–21 days; P = 0.001). However, main secondary outcomes, such as clinical cure, 28-day mortality, hospital mortality, and ICU and hospital stays were not different between the two groups. In cost evaluation, PCT-guided therapy decreased antibiotic costs by USD 30 (USD 241 in the PCT group vs. USD 270 in the control group). The results of the intention-to-treat analysis were similar to those obtained for the per-protocol analysis. CONCLUSION: PCT-guided antibiotic discontinuation in critically ill patients with sepsis could reduce the duration of antibiotic use and its costs with no apparent adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02202941
Anti-Bacterial Agents ; Biomarkers ; Calcitonin ; Costs and Cost Analysis ; Critical Illness ; Hospital Mortality ; Humans ; Intensive Care Units ; Length of Stay ; Mortality ; National Health Programs ; Prevalence ; Renal Replacement Therapy ; Sepsis

The study of the genus Streptomyces is of particular interest because it produces a wide array of clinically important bioactive molecules. The genomic sequencing of many Streptomyces species has revealed unusually large numbers of cytochrome P450 genes, which are involved in the biosynthesis of secondary metabolites. Many macrolide biosynthetic pathways are catalyzed by a series of enzymes in gene clusters including polyketide and non-ribosomal peptide synthesis. In general, Streptomyces P450 enzymes accelerate the final, post-polyketide synthesis steps to enhance the structural architecture of macrolide chemistry. In this review, we discuss the major Streptomyces P450 enzymes research focused on the biosynthetic processing of macrolide therapeutic agents, with an emphasis on their biochemical mechanisms and structural insights.

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.
Bevacizumab ; Budgets ; Endothelial Growth Factors ; Fees and Charges ; Humans ; Macular Edema ; National Health Programs ; Prescriptions ; Ranibizumab ; Vascular Endothelial Growth Factor A

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.
Diabetic Retinopathy ; Endothelial Growth Factors ; Health Expenditures ; Humans ; Intravitreal Injections ; National Health Programs ; Public Health ; Ranibizumab

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.
Diagnosis ; Endothelial Growth Factors ; Humans ; Insurance ; Intravitreal Injections ; Macular Degeneration ; National Health Programs ; Public Health ; Ranibizumab