Ameliorative effect of Abeliophyllum distichum Nakai on benign prostatic hyperplasia in vitro and in vivo

BACKGROUND/OBJECTIVES@#Benign prostatic hyperplasia (BPH) is the most common prostate disease and one of the most common chronic diseases caused by aging in men. On the other hand, there has been no research on BPH using Abeliophyllum distichum Nakai (A.distichum). Therefore, this study investigated the effects of A. distichum on BPH.MATERIALS/METHODS: A. distichum leaves were extracted with distilled water, 70% ethanol, and 95% hexane as solvents. Subsequently, the inhibitory effects of each A. distichum extract on androgen receptor (AR) signaling were evaluated in vitro. The testosterone-induced BPH model was then used to confirm the efficacy of A. distichum leaves in 70% ethanol extract (ADLE). @*RESULTS@#ADLE had the strongest inhibitory effect on AR signaling. A comparison of the activity of ADLE by harvest time showed that the leaves of A. distichum harvested in autumn had a superior inhibitory effect on AR signaling to those harvested at other times. In the BPH rat model, the administration of ADLE reduced the prostate size and prostate epithelial cell thickness significantly and inhibited AR signaling. Subsequently, the administration of ADLE also reduced the expression of growth factors, thereby inactivating the PI3K/AKT pathway. @*CONCLUSIONS@#An analysis of the efficacy of ADLE to relieve BPH showed that the ethanol extract grown in autumn exhibited the highest inhibitory ability of the androgen-signaling related factors in vitro. ADLE also inhibited the expression of growth factors by inhibiting the expression of the androgen-signaling related factors in vivo. Overall, ADLE is proposed as a functional food that is effective in preventing BPH.

Essential health care

The term “essential health care” is used as both an absolute concept and a relative concept. In countries with a high level of economic development, the implications of the relative concept of essential health care are generally more important, as the essential medical services included within the absolute concept are usually covered. The definition of essential health technologies as those that should be prioritized in public healthcare from a socioeconomic point of view is crucial for the process of in a timely manner. These determinations should be based on scientifically rigorous, comprehensive, and critical evaluations, including systematic reviews of the literature, and decision-making should proceed through a process of based on medical and socio-economic values. These decision-making processes should be transparent and consistent. In South Korea, the legal standard for decision-making by the health insurance program regarding whether mandates taking into account medical validity, medical, effectiveness, cost-effectiveness, patient cost burden, and social benefits. However, there are a number of committees that make coverage decisions, and there are no guidelines for standardized decision-making methods and procedures; therefore, it is urgently necessary to develop an explicit, detailed and specific decision-making guideline.

Reevaluation of the impact of methicillin-resistance on outcomes in patients with Staphylococcus aureus bacteremia and endocarditis

BACKGROUND/AIMS@#Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals, and has recently emerged in the community. The impact of methicillin-resistance on mortality and medical costs for patients with S. aureus bacteremia (SAB) requires reevaluation.@*METHODS@#We searched studies with SAB or endocarditis using electronic databases including Ovid-Medline, Embase-Medline, and Cochrane Library, as well as five local databases for published studies during the period January 2000 to September 2011.@*RESULTS@#A total of 2,841 studies were identified, 62 of which involved 17,563 adult subjects and were selected as eligible. A significant increase in overall mortality associated with MRSA, compared to that with methicillin-susceptible S. aureus (MSSA), was evidenced by an odds ratio (OR) of 1.95 (95% confidence interval [CI], 1.73 to 2.21; p < 0.01). In 13 endocarditis studies, MRSA increased the risk of mortality, with an OR of 2.65 (95% CI, 1.46 to 4.80). When three studies, which compared mortality rates between CA-MRSA and CA-MSSA, were combined, the risk of methicillin-resistance increased 3.23-fold compared to MSSA (95% CI, 1.25 to 8.34). The length of hospital stay in the MRSA group was 10 days longer than that in the MSSA group (95% CI, 3.36 to 16.70). Of six studies that reported medical costs, two were included in the analysis, which estimated medical costs to be $9,954.58 (95% CI, 8,951.99 to 10,957.17).@*CONCLUSIONS@#MRSA is still associated with increased mortality, longer hospital stays and medical costs, compared with MSSA in SAB in studies published since the year 2000.

Essential health care

The term “essential health care” is used as both an absolute concept and a relative concept. In countries with a high level of economic development, the implications of the relative concept of essential health care are generally more important, as the essential medical services included within the absolute concept are usually covered. The definition of essential health technologies as those that should be prioritized in public healthcare from a socioeconomic point of view is crucial for the process of in a timely manner. These determinations should be based on scientifically rigorous, comprehensive, and critical evaluations, including systematic reviews of the literature, and decision-making should proceed through a process of based on medical and socio-economic values. These decision-making processes should be transparent and consistent. In South Korea, the legal standard for decision-making by the health insurance program regarding whether mandates taking into account medical validity, medical, effectiveness, cost-effectiveness, patient cost burden, and social benefits. However, there are a number of committees that make coverage decisions, and there are no guidelines for standardized decision-making methods and procedures; therefore, it is urgently necessary to develop an explicit, detailed and specific decision-making guideline.

Appropriate off-label drug use

After new drugs are introduced into an area of medical practice through the regulatory approval process, clinicians gain further experience using the drugs and amass real-world evidence regarding their efficacy. For these reasons, drugs can be prescribed in contexts extending beyond their labeled indication, dosage, or route because of unmet needs or additional benefits, such as cost-effectiveness. Off-label drug use (OLDU) is widespread in various clinical fields, especially in pediatrics, obstetrics, psychiatry, and oncology; however, the small amount of supporting evidence associated with increased adverse drug events has emerged as an important issue regarding OLDU. Nonetheless, OLDU has officially been allowed in South Korea by an announcement of the Ministry of Health and Welfare, a public announcement of the Health Insurance Review and Assessment Service for cancer drugs, and through submissions to the Health Insurance Review and Assessment Service by hospitals after receiving institutional review board approval. Despite these systems, the proper scope of OLDU has been a topic of debate. In order to improve the appropriateness of OLDU, a transparent system for evidence-based recommendations, conditional decision-making, and monitoring of adverse drug events should be established and organized in collaboration with existing systems to promote consistent decision-making.

Appropriate off-label drug use

After new drugs are introduced into an area of medical practice through the regulatory approval process, clinicians gain further experience using the drugs and amass real-world evidence regarding their efficacy. For these reasons, drugs can be prescribed in contexts extending beyond their labeled indication, dosage, or route because of unmet needs or additional benefits, such as cost-effectiveness. Off-label drug use (OLDU) is widespread in various clinical fields, especially in pediatrics, obstetrics, psychiatry, and oncology; however, the small amount of supporting evidence associated with increased adverse drug events has emerged as an important issue regarding OLDU. Nonetheless, OLDU has officially been allowed in South Korea by an announcement of the Ministry of Health and Welfare, a public announcement of the Health Insurance Review and Assessment Service for cancer drugs, and through submissions to the Health Insurance Review and Assessment Service by hospitals after receiving institutional review board approval. Despite these systems, the proper scope of OLDU has been a topic of debate. In order to improve the appropriateness of OLDU, a transparent system for evidence-based recommendations, conditional decision-making, and monitoring of adverse drug events should be established and organized in collaboration with existing systems to promote consistent decision-making.

Effect of the Ethanol Extract of Propolis on Formation of Streptococcus mutans Biofilm

Streptococcus mutans (S. mutans) is one of the most important bacteria in the formation of dental plaque and dental caries. S. mutans adheres to an acquired pellicle formed on the tooth surface, and aggregates with many oral bacteria. It initiates plaque formation by synthesizing glucan from sucrose, which is catalyzed by glucosyltransferases. Propolis is a resinous mixture produced by honeybees, by mixing saliva and beeswax with secretions gathered from wood sap and flower pollen. Bees prevent pathogenic invasions by coating the propolis to the outer and inner surface of the honeycomb. Propolis has traditionally been used for the treatment of allergic rhinitis, asthma and dermatitis. We investigated the inhibitory effects of propolis ethanol extract on biofilm formation and gene expression of S. mutans. The biofilm formation of S. mutans was determined by scanning electron microscopy (SEM) and safranin staining. We observed that the extract of propolis had an inhibitory effect on the formation of S. mutans biofilms at concentrations higher than 0.2 mg/ml. Real-time PCR analysis showed that the gene expression of biofilm formation, such as gbpB, spaP, brpA, relA and vicR of S. mutans, was significantly decreased in a dose dependent manner. The ethanol extract of propolis showed concentration dependent growth inhibition of S. mutans, and significant inhibition of acid production at concentrations of 0.025, 0.05, 0.1 and 0.2 mg/ml, compared to the control group. These results suggest that the ethanol extract of propolis inhibits gene expression related to biofilm formation in S. mutans

Is Prostate-Specific Antigen Effective for Population Screening of Prostate Cancer? A Systematic Review

BACKGROUND: The effectiveness of prostate-specific antigen (PSA) for population screening has presented controversial results in large trials and prior reviews. We investigated the effectiveness of PSA population screening in a systematic review. METHODS: The study was conducted using existing systematic reviews. We searched Ovid MEDLINE, Embase, Cochrane library, and the major Korean databases. The quality of the systematic reviews was assessed by two reviewers independently using AMSTAR. Randomized controlled trials were assessed using the risk of bias tool in the Cochrane group. Meta-analyses were conducted using Review Manager. The level of evidence of each outcome was assessed using GRADE. RESULTS: Prostate-cancer-specific mortality was not reduced based on similar prior reviews (relative risk [RR] 0.93; 95% confidence interval [CI], 0.81-1.07, P=0.31). The detection rate of stage 1 prostate cancer was not greater, with a RR of 1.67 (95% CI, 0.95-2.94) and high heterogeneity. The detection rate of all cancer stages in the screening group was high, with a RR of 1.45 (95% CI, 1.13-1.85). No difference in all-cause mortality was observed between the screening and control groups (RR, 0.99; 95% CI, 0.98-1.01, P=0.50). Prostate-cancer-specific mortality, all-cause mortality, and diagnosis of prostate cancer at stages 3-4 showed moderate levels of evidence. CONCLUSIONS: Differently from prior studies, our review included updated Norrkoping data and assessed the sole effect of PSA testing for prostate cancer screening. PSA screening alone did not increase early stage prostate cancer detection and did not lower mortality.

Impact of Methicillin-Resistance on Mortality in Children and Neonates with Staphylococcus aureus Bacteremia: A Meta-analysis

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is the Staphylococcal infections in blood, one of the most common and fatal bacterial infectious diseases worldwide in adults as well as children or neonates. Recently, some studies have yielded inconsistent findings about the association between methicillin-resistance and mortality in patients with SAB. We performed a meta-analysis to assess the impact of methicillin-resistance on mortality in children or neonates with S. aureus bacteremia. MATERIALS AND METHODS: We searched using electronic databases such as Ovid-Medline, EMBASE-Medline, and Cochrane Library, as well as five local databases for published studies during the period of 1 January 2000 to 15 September 2011. Two reviewers independently selected articles in accordance with predetermined criteria and extracted prespecified data based on standardized forms. All cohort studies, which compared in-hospital mortality or SAB-related mortality in children and neonates with methicillin-resistant S. aureus (MRSA) infection to those with methicillin-susceptible S. aureus (MSSA), were included. We conducted meta-analysis using the fixed-effect model to obtain pooled estimates of effect. RESULTS: Of 2,841 screened studies, seven cohort studies were finally selected for analysis. In children or neonates, MRSA bacteremia was associated with a higher mortality compared with MSSA bacteremia (pooled odds ratio [OR] 2.33, P = 0.0008, 95% confidence interval [CI] 1.42 to 3.82, I2 = 0%). Four studies reported SAB-related mortality, the pooled OR of these studies was 2.03 (P = 0.29, 95% CI 0.55 to 7.53, I2 = 0%). A significant increase in mortality associated with methicillin resistance was found in the subgroup analyses of the studies with only neonates (OR: 2.66, 95% CI: 1.46 to 4.85, P = 0.001), prospectively design ones (OR: 3.20, 95% CI: 1.66 to 6.15, P = 0.0005,), the larger studies (OR: 2.89, 95% CI: 1.62 to 5.16, P = 0.0003) and the higher quality studies (OR: 2.76, 95% CI: 1.50 to 5.06, P = 0.001). CONCLUSIONS: MRSA bacteremia is associated with increased mortality compared with MSSA bacteremia in children or neonates. Due to limited studies for mortality in children or neonates with SAB, further research is needed to evaluate the impact of methicillin resistance on mortality in those populations.

Use of Drug-eluting Stents Versus Bare-metal Stents in Korea: A Cost-minimization Analysis Using Population Data / 예방의학회지

OBJECTIVES: The goal of this study was to perform an economic analysis of a primary stenting with drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients with acute myocardial infarction (AMI) admitted through an emergency room (ER) visit in Korea using population-based data. METHODS: We employed a cost-minimization method using a decision analytic model with a two-year time period. Model probabilities and costs were obtained from a published systematic review and population-based data from which a retrospective database analysis of the national reimbursement database of Health Insurance Review and Assessment covering 2006 through 2010 was performed. Uncertainty was evaluated using one-way sensitivity analyses and probabilistic sensitivity analyses. RESULTS: Among 513 979 cases with AMI during 2007 and 2008, 24 742 cases underwent stenting procedures and 20 320 patients admitted through an ER visit with primary stenting were identified in the base model. The transition probabilities of DES-to-DES, DES-to-BMS, DES-to-coronary artery bypass graft, and DES-to-balloon were 59.7%, 0.6%, 4.3%, and 35.3%, respectively, among these patients. The average two-year costs of DES and BMS in 2011 Korean won were 11 065 528 won/person and 9 647 647 won/person, respectively. DES resulted in higher costs than BMS by 1 417 882 won/person. The model was highly sensitive to the probability and costs of having no revascularization. CONCLUSIONS: Primary stenting with BMS for AMI with an ER visit was shown to be a cost-saving procedure compared with DES in Korea. Caution is needed when applying this finding to patients with a higher level of severity in health status.

Clinical Trials and Accuracy of Diagnostic Tests

Most clinicians understand clinical trials as the evaluation process for new medicine before their use. However, clinical trials can also be applied to laboratory diagnostic tests (LDTs) to verify diagnostic accuracy and efficacy before their clinical laboratory implementation for patients. The clinical trial of LDT has two distinctive characteristics that are different from the case of pharmaceuticals and thus worth special consideration. One of them is the level of evidence. The well-designed randomized controlled trials (RCTs) are known to provide the best evidence to prove the clinical efficacy of any pharmaceutical products. However, RCTs lose practicality when applied to LDTs due to various issues including ethical complications. For this reason, comparative study format is considered more feasible approach for LDTs. In addition pharmaceuticals and LDTs are different in that the user's intervention is not required for the former but critical to the latter. Moreover, in the case of pharmaceuticals, end-products are produced by manufacturers before being used by clinicians. However, in LDTs, once reagents and instruments are provided by manufacturers, they are first utilized by clinical laboratories to produce test results in order for clinicians to use them later. In other words, when it comes to LDTs, clinical laboratories play the role of manufacturers, providing reliable test results with improved quality assurance. Considering the distinctive characteristics of LDTs, we would like to offer detailed suggestions to successfully perform clinical trials in LDTs, which include analytical performance measures, clinical test performance measures, diagnostic test accuracy measures, clinical effectiveness measures, and post-implementation surveillance.

Evidence-based healthcare and the need of conditional decision

The decision making for reimbursement has become more difficult than before because of the high cost innovative new technologies and limitation of healthcare resources. Evidence-based healthcare system has been introduced in Korea since 2007. Not infrequently, however, decision makers have been confronted with uncertainties caused by lack of information related to comparative effectiveness, real world outcomes, off-label drug use, combination therapy and cost-effectiveness. Under these circumstances, the decision making of whether or not to reimburse is inadequate because undesirable results may be induced. Managed entry agreement has been introduced globally. This kind of decision is conditional and linked with monitoring and following the results and adjusting the policy according to the results. Especially access with evidence development is a form of prospective data correction with conditional coverage in the case of existing uncertainties of effectiveness and safety. In Korea, there have been several examples including off-label drug use in oncologic drugs, new healthcare intervention and re-evaluation of existing drugs. Even though there has been some conflict and confusion because of inadequate systematization, it is strongly recommended to establish the conditional decision making system in Korea since this is a unique answer to manage the uncertainty in maintaining development of health science, keeping patients' right and using healthcare resources rationally.

A Case of Purpura Associated with Levetiracetam / 대한간질학회지

Levetiracetam has not been reported to cause purpura. We report a case of purpura associated with levetiracetam. A 81-year-old man suffered from post-stroke seizure. Seizure was well controlled with valproate. Valproate was discontinued due to pancytopenia and levetiracetam was prescribed when he was admitted with pneumonia. A few days later, he recovered from pancytopenia and pneumonia. However, he was rehospitalized due to multiple variable sized-purpura on the whole body surface without thrombocytopenia. After discontinuing levetiracetam, purpura disappeared.

Treatment Guidelines for Community-acquired Pneumonia in Korea: An Evidence-based Approach to Appropriate Antimicrobial Therapy / 결핵및호흡기질환

The successful treatment of community-acquired pneumonia requires appropriate, empirical antimicrobial therapy. The etiology and antimicrobial susceptibility of major pneumonia pathogens can differ by country. Therefore, the ideal treatment guidelines for community-acquired pneumonia should be based on the studies performed in each country. We developed a treatment guideline for community-acquired pneumonia for immunocompetent adults in Korea. This guideline was developed by the joint committee of the Korean Society for Chemotherapy, the Korean Society of Infectious Diseases, and the Korean Academy of Tuberculosis and Respiratory diseases.

Treatment Guidelines for Community-acquired Pneumonia in Korea: An Evidence-based Approach to Appropriate Antimicrobial Therapy

A successful therapy of community-acquired pneumonia requires appropriate empirical antimicrobial therapy. Etiology and antimicrobial susceptibility of major pathogens of pneumonia can differ by country. Therefore, an ideal treatment guideline of community-acquired pneumonia should be based on the studies performed in each country. We developed a treatment guideline for community-acquired pneumonia in immunocompetent adults in Korea. This guideline was developed by the joint committee of the Korean Society for Chemotherapy, the Korean Society of Infectious Diseases, and the Korean Academy of Tuberculosis and Respiratory diseases.

Treatment Guidelines for Community-acquired Pneumonia in Korea: An Evidence-based Approach to Appropriate Antimicrobial Therapy

A successful therapy of community-acquired pneumonia requires appropriate empirical antimicrobial therapy. Etiology and antimicrobial susceptibility of major pathogens of pneumonia can differ by country. Therefore, an ideal treatment guideline of community-acquired pneumonia should be based on the studies performed in each country. We developed a treatment guideline for community-acquired pneumonia in immunocompetent adults in Korea. This guideline was developed by the joint committee of the Korean Society for Chemotherapy, the Korean Society of Infectious Diseases, and the Korean Academy of Tuberculosis and Respiratory diseases.

Reversible Abducens Nerve Palsy Following Transvenous Embolization of Cavernous Sinus Dural Arteriovenous Fistula

Transvenous embolization has become the treatment of choice for cavernous sinus dural arteriovenous fistula(cDAVF). However, there are potential complications associated with this procedure such as cranial nerve palsies and venous perforations. A 66-year-old woman presented with a 2-week left periorbital swelling and conjunctival injection. Brain MRI showed engorgement of the left superior ophthalmic vein. Cerebral angiography revealed a dural arteriovenous shunt of the cavernous sinus with retrograde venous drainage into the superior ophthalmic vein. Her proptosis and conjunctival injection resolved completely after transvenous embolization of cDAVF. However, an abducens nerve palsy developed the day after the procedure, which, fortunately, resolved spontaneously. She was symptom-free at the follow- up evaluation 2 months later. The abducens nerve palsy related to the transvenous embolization of cDAVF was presu- med due to either dense packing of the sinus, venous thrombosis, or direct nerve injury. We report a case of transient abducens nerve palsy associated with transvenous embolization of cDAVF, suggesting the benign course of this com- plication.

Evidence-Based Healthcare: Seeking for the Broken Virtuous Circle

Several hot issues boiled our healthcare system in these years: off-label drug use, DUR, reuse of single-use devices (SUD), and conflicts in adopting new health technologies. Perhaps, most of conflicts among the stakeholders and policy makers of healthcare system can be explained by lack of communications and unsatisfactory efforts to understand each other. Evidence-based healthcare might be a solution, a common language to talk each other. Hence, it is worthwhile to assemble a strategic approach of evidence generation and synthesis of evidence. Furthermore, the introduction of conditional coverage decision in the national health insurance system is necessary to deal with uncertainty. To summarize, proper synthesis of evidence and a prudent use of it along with social values in decision making process is an answer to the conflicts. Now is the time to advance to a virtuous cycle of evidence-based healthcare.

A Case of Oxcarbazepine Induced Beau's Line / 대한간질학회지

Beau's line is a grooved transverse line on the fingernail or toenail, and is considered as a kind of nail disorder, It is known to occur with temporary arrest of nail matrix proliferation. The causes of Beau's line comprise severe systemic illness as well as drug ingestion. A 51-year-old male patient had developed Beau's line on all his fingers after about three months of oxcarbazepine administration. These nail changes disappeared spontaneously with nail growth two months later. The authors report a case of oxcarbazepine induced Beau's line.

A Case of Recurrent Hepatic Encephalopathy Secondary to Spontaneous Intrahepatic Portosystemic Venous Shunt

The portosystemic venous shunts within the hepatic parenchyma, a rare disease can lead to hepatic encephalopathy. The etiology of intrahepatic portosystemic venous shunt may be either congenital or acquired such as secondary to portal hypertension due to chronic liver damage. A 61-year-old women was admitted to our hospital with recurrent encephalopathy. Liver function tests, abdominal computerized tomography, ultrasound and arterial portography revealed an intrahepatic portosystemic venous shunt in a noncirrhotic liver. Thus, recurrent encephalopathy should be closely evaluated for detection of rare causes.