Search

Purpose: Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review and meta-analysis to summarize and synthesize the available evidence on the efficacy and safety of fixed-dose combination (FDC) therapy with netarsudil/latanoprost in patients with glaucoma.Methods: We identified relevant studies in PubMed, Ovid Medline, Embase, and Cochrane Central until April 2021. The quality of the studies and the level of evidence were assessed using the Risk of Bias tool. Efficacy was measured as the mean difference in reducing intraocular pressure (IOP), and safety was assessed by the risk of conjunctival hyperemia (CH) due to FDC therapy, netarsudil monotherapy, or latanoprost monotherapy.Results: Four studies met the predefined eligibility criteria and were included in the meta-analysis. The mean difference in the reduction in IOP after 2 weeks and 4 to 6 weeks of drug administration was -2.41 mmHg (95% confidence interval [CI], -2.95 to -1.87) and -1.77 mmHg (95% CI, -2.31 to -1.87), respectively, in patients receiving FDC therapy versus those receiving latanoprost monotherapy. On the other hand, latanoprost monotherapy had a greater effect in reducing IOP than netarsudil monotherapy after 4 to 6 weeks of administration (mean difference, 0.95 mmHg; 95% CI, 0.43 to 1.47). The risk of CH was significantly higher with both FDC therapy and netarsudil monotherapy compared to latanoprost monotherapy in week 12, where the relative ratio was 3.01 (95% CI, 1.95 to 4.66) and 2.33 (95% CI, 1.54 to 3.54), each.Conclusions: Netarsudil/latanoprost FDC therapy has a significantly greater effect on reducing IOP than latanoprost alone. The symptoms of CH were mostly mild, and only a few glaucoma patients discontinued the medication owing to CH in earlier clinical trials. Therefore, it would be beneficial to consider the administration of netarsudil/latanoprost FDC therapy in patients with glaucoma.

Background: Long-term levodopa administration for treating Parkinson’s disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy. Objective: We provide pooled scientific evidence highlighting the efficacy and safety of opicapone, a newly approved COMT inhibitor, as an adjuvant to levodopa. Methods: We searched Ovid Medline, Embase, and Cochrane databases for relevant reports. Efficacy and safety were evaluated as off-time reduction and risk ratio (RR) of dyskinesia, respectively. Data were independently extracted using predefined criteria. Selected placebo-controlled trials were divided into double-blind and open-label periods. Using a random-effects model, the mean difference (MD) of the off-time reduction (efficacy), RR for the occurrence of dyskinesia, and on-time without/with troublesome dyskinesia (TD; safety assessment) were compared between opicapone and placebo groups. Results: Five studies from three randomized controlled trials were included, and a meta-analysis was performed with 407 patients receiving opicapone 50 mg and 402 patients receiving placebo. Compared with the placebo, opicapone (50 mg) reduced off-time by 49.91 min during the double-blind period (95% confidence intervals [CIs] = –71.39, –28.43; I2 = 0%). The RR of dyskinesia was 3.43 times greater in the opicapone 50 mg group than in the placebo group (95% CI = 2.14, 5.51; I = 0%). Compared with the placebo, opicapone increased the on-time without TD by 44.62 min (95% CI = 22.60, 66.64; I2 = 0%); the on-time increase with TD did not differ between treatments. Conclusion: Opicapone can play a positive role as an adjuvant to levodopa in patients with PD by reducing off-time and prolonging on-time without PD.

Purpose Health-related quality of life (HRQoL) is an important construct in clinical settings, and it is crucial that it should be properly measured. As the EuroQol-5-dimensions-5 levels (EQ-5D-5L) is more effective for such measurement than the 3-level model, data on economic models, clinical studies, and public health evaluations previously collected through the EQ-5D-3L need to be revaluated using the EQ-5D-5L. This study evaluated colorectal cancer (CRC) patients’ HRQoL scores using the Vietnamese EQ-5D-5L value set. Patients and Methods The cross-sectional study included CRC patients treated at a tertiary public hospital. HRQoL was assessed using the EQ-5D-5L, and HRQoL utility scores were calculated using the Vietnamese value set. Tobit regression examined factors associated with HRQoL. Results The analysis included 197 CRC patients. Ages ranged from 20 to 87 years (M = 57.64, SD = 13.5); 42.2% and 57.8% were diagnosed with cancer of the colon or rectum/anus, respectively. Mean EQ-5D-5L was 0.561 (range, −0.5115 to 1). Most participants experienced anxiety/depression (88%), followed by pain/discomfort (87%), mobility (71%), usual activity (69%), and self-care (67%). Advanced CRC stage (stage II: β −0.303, se 0.08; stage III: β −0.305, se 0.07; stage IV: β −0.456, se 0.07) and surgery (β −0.113, se 0.05) were negatively associated with EQ-5D-5L scores. Advanced education (high school: β 0.273, se 0.07); college/vocational: β 0.134se 0.05; university/higher: Coef 0.213, se 0.08;) and older age (age group 35−44: β 0.253, se 0.10; 45−54: β 0.327, se 0.09; 55−64: β 0.355 se 0.09; 65+ β 0.204, se 0.09) were positively associated with EQ-5D-5L scores. Conclusion Patients in advanced CRC stages or undergoing surgery experienced lower HRQoL and higher prevalence of anxiety/depression and pain/discomfort. Older age and high educational attainment predicted high HRQoL. This study provides information on CRC patients’ health utility based on various patient characteristics, which can be used in future economic evaluations.

Background/Aims: Inhibitors of the renin-angiotensin system, angiotensin-con verting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), reportedly have anti-inflammatory effects. This study assessed the association of prior use of ACE inhibitors and ARBs with sepsis-related clinical outcomes. Methods: A population-based observational study was conducted using the Health Insurance Review and Assessment Service claims data. Among the adult patients hospitalized with new onset of sepsis in 2012, patients who took ARBs or ACE inhibitors at least 30 days prior to hospitalization were analyzed. Generalized linear models and logistic regression were used to examine the relation between the prior use of medication and clinical outcomes, such as in-hospital mortality, mechanical ventilation, and length of stay. Results: Of a total of 27,628 patients who were hospitalized for sepsis, the ACE in hibitor, ARB, and non-user groups included 1,214 (4.4%), 3,951 (14.4%), and 22,463 (82.1%) patients, respectively. As the patients in the ACE inhibitor and ARB groups had several comorbid conditions, higher rates of intensive care unit admission, hemodialysis, and mechanical ventilation were observed. However, after covariate adjustment, the use of ACE inhibitor (odds ratio [OR], 0.752; 95% confidence inter val [CI], 0.661 to 0.855) or ARB (OR, 0.575; 95% CI, 0.532 to 0.621) was significantly associated with a lower rate of in-hospital mortality. Conclusions: Pre-hospitalization use of ACE inhibitors or ARBs for sepsis was an independent factor for a lower rate of in-hospital mortality.

bBackground/Aims:/bThe National Liver Cancer Surveillance Program (NLCSP) was established in 2003 to reduce the socioeconomic burden imposed by liver cancer (LC). We aimed to investigate the effectiveness of the NLCSP in South Korea with respect to survival benefits and cost, after adjusting for various confounding factors.bMethods:/bWe used the National Health Insurance Service claims data linked with the NLCSP from 2004 to 2015. The Cox proportional hazard model and generalized linear model were used to determine the effects of the NLCSP on the early detection of LC, survival, and medical costs.bResults:/bFrom 2006 to 2010, 66,632 patients (surveillance group: 10,527 and no surveillance group: 56,105) newly diagnosed with LC were included in the study. The odds of the early detection of LC was 1.82 (95% confidence interval [CI], 1.73 to 1.93) times higher among patients who participated in the NLCSP once within the 2-year period prior to the diagnosis of LC than among those who did not participate in the surveillance program. The mortality rate of patients who participated in the NLCSP was 22.0% lower (hazard ratio, 0.78; 95% CI, 0.76 to 0.80) than that of those who did not participate. When compared with the group who did not participate in surveillance, the group who participated in the NLCSP had higher total medical costs; however, their cost per day was lower after adjustment during the follow-up period.bConclusions:/bThis study highlights the survival benefit in patients who participated in the NLCSP and the need for continuous improvements of the NLCSP in South Korea.

Background:Presently, there are no national screening programs for cancer in Vietnam. This study aimed to analyze the cost-effectiveness of an annual colorectal cancer (CRC) screening program from ...

Background Controversies remain regarding clinical outcomes following initial strategies of coronary computed tomography angiography (CCTA) vs usual care with functional testing in patients with suspected coronary artery disease (CAD). Hypothesis CCTA as initial diagnostic strategy results in better mid- to long-term outcomes than usual care in patients with suspected CAD. Methods We searched PubMed, Embase, and Cochrane Library for randomized controlled trials comparing clinical outcomes during ≥6 months' follow-up between initial anatomical testing by CCTA vs usual care with functional testing in patients with suspected CAD. Occurrence of all-cause mortality, nonfatal myocardial infarction (MI), and major adverse cardiovascular events (MACE), and use of invasive coronary angiography and coronary revascularization, were compared between the 2 diagnostic strategies. Results Twelve trials were included (20 014 patients; mean follow-up, 20.5 months). Patients undergoing CCTA as initial noninvasive testing had lower risk of nonfatal MI compared with those treated with usual care (risk ratio [RR]: 0.70, 95% confidence interval [CI]: 0.52-0.94, P = 0.02). There was a tendency for reduced MACE following initial CCTA strategy, but not for risk of all-cause mortality. Compared with functional testing, the CCTA strategy increased use of invasive coronary angiography (RR: 1.53, 95% CI: 1.12-2.09, P = 0.007) and coronary revascularization (RR: 1.49, 95% CI: 1.11-2.00, P = 0.007). Conclusions Anatomical testing with CCTA as the initial noninvasive diagnostic modality in patients with suspected CAD resulted in lower risk of nonfatal MI than usual care with functional testing, at the expense of more frequent use of invasive procedures.

Objective This study aimed to determine whether the rate of clozapine use, an indicator of refractoriness in schizophrenia, is associated with the season of birth and age at onset in patients with schizophrenia based on nationwide data. Methods Patients with schizophrenia (n = 114 749) who received prescriptions for antipsychotic medication between 2008 and 2014 were retrospectively identified from the Korean National Health Insurance Service database. The study population was divided into three groups based on their age at the onset of schizophrenia (early, middle, and late onset). We assessed differences in the month of birth between patients and the general population. In addition, the cumulative clozapine use was calculated. Results Compared to the late-onset schizophrenia group, the early- and middle-onset groups showed a higher probability of birth during the winter season. In addition, the early-onset group showed the highest cumulative clozapine use rate. In the middle-onset group, the initiation of clozapine use was significantly earlier for patients born in winter compared to those born in summer. Conclusion Our results indicate that the age at onset is an important factor in predicting the prognosis of schizophrenia patients. The season of birth also affects the prognosis, but with less robustness. Specifically, it appears that early disease onset and winter birth might be associated with poor outcomes in Korean patients with schizophrenia.

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, Graphical Abstract

The incidence and mortality of colorectal cancer (CRC) has increased rapidly in Vietnam, but the economic burden of this disease has never been estimated. We estimate the direct and indirect cost of CRC patients in Vietnam in 2018 using a prevalence-based approach and human capital method. The total economic cost of CRC was VND 3041.88 billion (~$132.9 million), representing 0.055% of the 2018 gross domestic product. Notably, indirect costs comprised 83.58 % of the total cost, 82.61% of which is future income loss, because CRC occurs during productive years. The economic burden of CRC in Vietnam is substantial. The medical cost for CRC diagnosis and treatment is higher for younger patients and for those in advanced stages. Strategies to decrease the economic burden of CRC at the patient and national level, such as screening programs, should be developed and implemented in Vietnam.

Background The National Liver Cancer Surveillance Program (NLCSP) targets patients with liver diseases that lead to liver cancer in South Korea. This study aimed to investigate the risk of liver disease leading to liver cancer using nationally representative data to establish an efficient NLCSP. Methods This study used data from the National Health Insurance Service National Sample Cohort (NHIS-NSC) from 2002 to 2013. A retrospective matched cohort design was applied to compare the development of liver cancer in patients with and without liver disease. Cox- proportional hazard regression for liver cancer with competing risk of death was performed for all subjects or each group stratified according to age or income level. Results A total of 66,192 patients with liver disease and matched subjects without liver disease were included in the study. The incidences of liver cancer among patients with and without liver disease within a median 8-year follow-up period were 2.68% (n = 1,772) and 0.34% (n = 210), respectively. Cox- regression analysis for liver cancer incidence indicated that cirrhosis had the highest risk (hazard ratio [HR]: 18.13, 95% confidence interval [CI]: 15.24-21.58), followed by hepatitis B (HR: 9.32, 95% CI: 8.00-10.85). Subgroup analysis showed that the presence of liver disease was an important risk factor in younger as well as elderly people, and a higher risk of liver disease was also observed in the patients with Medicaid. Conclusions Attention should be paid to the development of liver cancer in young people under 50 years old and preventive efforts to decrease the incidence of liver cancer among Medicaid recipients is needed.

We previously reported that transgenic (TG) mice over-expressing translationally controlled tumor protein (TCTP) developed systemic arterial hypertension at about 6 weeks after birth. In the present study, we identified, using proteomics technologies, 24 other proteins that were differentially expressed in the heart of TCTP over-expressing TG mice. These 24 proteins are involved in a variety of biological processes such as reactive oxygen species metabolism, cytoskeleton organization, fatty acid metabolism, amino acid metabolism and energy metabolism. We determined protein expression levels of the peroxiredoxin (Prx)2, Prx3, myosin light chain 1, stress protein (heat shock protein) 25K, and T-complex protein 1 alpha subunit by western blot analysis. Over-expression of TCTP probably regulates the expression of other proteins which play a pivotal role in a variety of cellular functions in TCTP over-expressing TG mice.

Inhibition of Na + ,K + -ATPase has been implicated in the pathogenesis of hypertension via its effect on smooth muscle reactivity and myocardial contractility. We recently demonstrated that translationally controlled tumor protein (TCTP) interacts with the 3rd cytoplasmic domain of Na + ,K + -ATPase α 1 -subunit and acts as its cytoplasmic repressor. Therefore, we hypothesized that repression of Na + ,K + -ATPase by overexpressed TCTP might underlie the development of hypertension. In the present study, we confirmed that transgenic mice overexpressing TCTP developed systemic arterial hypertension at about 6 weeks after birth. Vascular smooth muscle of TCTP-overexpressing transgenic mice also displayed augmented contractile response to vasoconstrictors and attenuated relaxation response to vasodilators. These responses seem to be caused by reduced Na + ,K + -ATPase activity and increased intracellular calcium, suggesting that inhibition of Na + ,K + -ATPase by overexpression of TCTP is involved in the pathogenesis of hypertension. This study provides a new link between alteration of sodium pump activity and hypertension in vivo , and suggests that TCTP might be a therapeutic target for the treatment of hypertension.

We previously reported that phosphorylated cofilin-triosephosphate isomerase (TPI) complex interacts with Na,K-ATPase and enhances the pump activity through the phosphorylation of cofilin via Rho-mediated signaling pathway. In this study, we tested the hypothesis that the dephosphorylation of cofilin may be induced through Na,K-ATPase inhibition by ouabain. The phosphorylation level of cofilin by ouabain which decreases in a time- and dose-dependent manner in various human cell lines, remains unchanged by pretreatment with Src inhibitor, PP2; epidermal growth factor receptor (EGFR) inhibitor, AG1478; Raf-1 kinase (Raf) inhibitor, GW5074; and ERK kinase (MEK) inhibitor, PD98059, and by transfection of Ras dominant negative mutant (RasN17). This suggests that ouabain dephosphorylates cofilin through the Src/EGFR/Ras/Raf/MEK pathway. Ouabain activates Ras/Raf/MEK pathway, but down-regulates Rho kinase (ROCK)/LIM kinase (LIMK)/cofilin pathway, implying that there may be a cross-talk by ouabain between the Ras/Raf/MEK and the ROCK/LIMK/cofilin pathways. Immunofluorescence and flow cytometry suggest that ouabain-induced active form of cofilin may be involved in cytoskeletal reorganization and cell volume regulation. Thus, these findings demonstrate a new molecular mechanism for the dephosphorylation of cofilin through the inhibition of Na,K-ATPase by ouabain.