Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are widely used for common cold symptom relief. The objective of this study was to evaluate and compare the efficacy and safety of acetaminophen and NSAIDs in common cold symptom relief using meta-analysis of randomized controlled trial.
We searched MEDLINE (PubMed), Cochrane, EMBASE, CINAHL, KMbase, KoreaMed, National Assembly Library, and Riss4u for studies released through June 2012. Two authors independently extracted the data. To assess the risk of bias, the Cochrane Collaborations risk of bias tool was used. The Review Manager ver. 5.1 (RevMan) was used for statistics.
We identified 5 studies. The relative benefit for participants with pain relief was 1.00 (95% confidence interval [CI], 0.96 to 1.05) and I2 = 0%. The existence of the heterogeneity between studies was not important in this study, thus subgroup analysis was not implemented. The relative benefit for participants with rhinorrhea was 1.02 (95% CI, 0.77 to 1.35) and I2 = 0%, which also indicates the existence of heterogeneity was not important. The relative risk of adverse events was 1.14 (95% CI, 0.93 to 1.40), I2 = 0%. There was no apparent asymmetry in the funnel plot.
There was no difference between NSAIDs and acetaminophen in common cold symptom relief.
Common Cold; Non-Steroidal Anti-Inflammatory Agents; Acetaminophen; Meta-Analysis
Probiotics are currently under focus for their immune improvement function. Many studies have been performed to assess the potential efficacy of probiotics in allergic disease, viral disease, respiratory disease, as well as gastrointestinal disease. This study performed a systematic review to determine the effects of probiotics on the prevention of the common cold.
We searched MEDLINE (PubMed), EMBASE, CINAHL, and Cochrane CENTRAL for studies released through June 2011. Two authors independently extracted the data. To assess the risk of bias of included literatures, Cochrane Collaboration's risk of bias tool was used.
We identified 10 studies in 7 articles. A total 2,894 participants, 1,588 in the probiotics group and 1,306 in the control group, were included. The effect of probiotics on the prevention of the common cold had a relative risk (RR) of 0.92 (95% CI, 0.85 to 1.00, I2 = 26%). In the subgroup analysis, the RR of administration of probiotics for 3 months or less was 0.82 (95% CI, 0.70 to 0.97). The RR of administration of probiotics over 3 months was 1.00 (95% CI, 0.92 to 1.09). The RR of administration of probiotics without any active intervention (vitamin and mineral) was 0.87 (95% CI, 0.78 to 0.97).
In this meta-analysis, there was marginal effect of probiotics on the prevention of the common cold. The results implied that probiotics had a modest effect in common cold reduction. The balance of benefit and harms needs to be considered when using probiotics for common cold prevention.
Probiotics; Common Cold; Meta-Analysis
Having usual source of care has been associated with improved receipt of preventive services and control of chronic diseases (such as hypertension, diabetes, and hypercholesterolemia). The objective of this study was to examine whether having usual source of care is associated with improved receipt of preventive services and control of chronic diseases.
We searched MEDLINE, EMBASE, Cochrane, CINAHL, KMbase, KoreaMed, RiSS4U, National Assembly Library, and KISS for studies released through May 31st 2011. Two authors independently extracted the data. We manually searched the references and twenty recent related articles on PubMed. To assess the risk of bias RoBANS tool was used.
We identified 10 studies. Most having usual source of care were associated with improved receipt of preventive services (cervical cancer screening, clinical breast exam, mammogram, prostate cancer screening, and flu shot) compared with no usual source of care. However, gastric cancer and colon cancer screening were difficult to conclude and blood pressure checkup showed mixed results. Overall there was no association between having usual source of care and smoking behaviors and the effect on chronic disease control was difficult to conclude.
Having usual source of care was associated with improved receipt of preventive services and overall the results were consistent. So, the results suggested that having usual source of care may help to receive preventive services. Hereafter, cohort studies are needed to evaluate casual relationships and more studies are needed in various countries and systems.
Usual Source of Care; Preventive Services; Chronic Disease Control; Systematic Review
Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are widely used in the treatment of tension headache. The objective of this study was to evaluate and compare the efficacy and safety of single doses of acetaminophen and NSAIDs using meta-analysis of randomized placebo-controlled trial studies.
We searched MEDLINE, EMBASE, CINAHL, Cochrane, KMbase, KoreaMed, RiCH, National Assembly Library, Riss4u, and DBPIA for studies released through 27th July 2010. Two authors independently extracted the data. To assess the risk of bias, the Cochrane Collaborations risk of bias tool was used. Review Manager 5.0 was used for statistics.
We identified 6 studies. The relative benefit of the NSAIDs group compared to the acetaminophen group for participants with at least 50% pain relief was 1.18 (95% confidence interval [CI], 0.99 to 1.39; I2 = 85%). We did subgroup analysis based on allocation concealment versus non-allocation concealment, and low-dose NSAIDs versus high-dose NSAIDs. The relative benefit of the low-dose NSAIDs subgroup to the acetaminophen group was 0.98 (95% CI, 0.91 to 1.06; I2 = 0%). However, the heterogeneity of other subgroup analysis was not settled. The relative risk for using rescue medication of the NSAIDs group compared to the acetaminophen group was 0.84 (95% CI, 0.64 to 1.12; I2 = 47%). The relative risk for adverse events was 1.31(95% CI, 0.96 to 1.80; I2 = 0%).
In this meta-analysis, there was no difference between low-dose NSAIDs and acetaminophen in the efficacy of the treatment for tension type headache. The results suggested that high-dose NSAIDs have more effect but also have more adverse events. The balance of benefit and harm needs to be considered when using high-dose NSAIDs for tension headache.
Tension-type Headache; Non-steroidal Anti-inflammatory Drugs; Acetaminophen; Meta-analysis
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement was developed to improve the reporting of observational studies. We aimed to evaluate the quality of reporting in cohort studies and case-control studies among observational studies published in the Korean Journal of Family Medicine.
We searched for cohort studies and case-control studies published as original articles in the Journal of the Korean Academy of Family Medicine during the period January 1992 through December 2009. The main outcome measures were the number and proportion of cohort studies and case-control studies that reported each of 22 checklist items of STROBE.
We identified a total of 84 articles, of which 46 articles were cohort studies and 38 were case-control studies. Concerning methods, study designs (10%), bias (13%), study size (0%), statistical methods (12-c and 12-e items, 0%; 12-d item, cohort study, 6%) have been poorly reported. Of results, participants (5-6%), descriptive data (14-b item, 5%), and funding (1%) among other information have been poorly reported.
The degree of adherence the STROBE recommendations was relatively low in cohort studies and case-control studies published in the Korean Journal of Family Medicine. An effort to improve the reporting of observational studies by application and recommendation of the STROBE statement is required.
Korean Journal of Family Medicine; Cohort Studies; Case-Control Studies; STROBE; Quality of Reporting
In reporting results of case-control studies, odds ratios are useful methods of reporting findings. However, odds ratios are often misinterpreted in the literature and by general readers.
We searched all original articles which were published in the Korean Journal of Family Medicine from 1980 to May 2011 and identified those that report "odds ratios." Misinterpretation of odds ratios as relative risks has been identified. Estimated risk ratios were calculated when possible and compared with odds ratios.
One hundred and twenty-eight articles using odds ratios were identified. Among those, 122 articles were analyzed for the frequency of misinterpretation of odds ratios as relative risks. Twenty-two reports out of these 122 articles misinterpreted odds ratios as relative risks. The percentage of misinterpreting reports decreased over years. Seventy-seven reports were analyzed to compare the estimated risk ratios with odds ratios. In most of these articles, odds ratios were greater than estimated risk ratios, 60% of which had larger than 20% standardized differences.
In reports published in the Korean Journal of Family Medicine, odds ratios are frequently used. They were misinterpreted in part of the reports, although decreasing trends over years were observed.
Odds Ratio; Relative Risk; Korean Journal of Family Medicine; Misinterpretation
Duplicate publication is considered unethical. It has several negative impacts. To estimate the frequency and characteristics of duplicate publications in Korean medical journals, we reviewed some portion of Korean journal articles. Among 9,030 articles that are original articles indexed in KoreaMed from January to December 2004, 455 articles (5%) were chosen by random sampling. PubMed, Google scholar, KMbase, and KoreaMed were searched by two librarians. Three authors reviewed titles, abstracts, and full text of index articles and suspected articles independently. Point of disagreement were reconciled by discussion. Criteria for a duplicate publication defined by editors of cardiothoracic journals and International Committee of Medical Journal Editors were used. A total of 455 articles were evaluated, of which 27 (5.93%) index articles were identified with 29 duplicate articles. Among 27 index articles, 1 was quadruple publication and 26 were double publications. Of 29 duplicated articles, 19 were classified as copy, 4 as fragmentation, and 6 as disaggregation. The proportion of duplicate publications in Korean medical journals appears to be higher than expected. Education on publication ethics to researchers is needed.
Duplicate Publication as Topics; Korea; Periodicals as Topic; Publishing
The protection of the brain from blood-borne toxins, proteins, and cells is critical to the brain’s normal function. Accordingly, a compromise in the blood–brain barrier (BBB) function accompanies many neurologic disorders, and is tightly associated with brain inflammatory processes initiated by both infiltrating leukocytes from the blood, and activation of glial cells. Those inflammatory processes contribute to determining the severity and prognosis of numerous neurologic disorders, and can both cause, and result from BBB dysfunction. In this review we examine the role of BBB and inflammatory responses, in particular activation of transforming grown factor β (TGFβ) signaling, in epilepsy, stroke, and Parkinson’s disease.
Blood–brain barrier; Epileptogenesis; Inflammation; TGF-beta; Cholinergic system
Amacrine and horizontal interneurons integrate visual information as it is relayed through the retina from the photoreceptors to the ganglion cells. The early steps that generate these interneuron networks remain unclear. Here we show that a distinct RORβ1 isoform encoded by the retinoid-related orphan nuclear receptor β gene (Rorb) is critical for both amacrine and horizontal cell differentiation in mice. A fluorescent protein cassette targeted into Rorb revealed RORβ1 as a novel marker of immature amacrine and horizontal cells and of undifferentiated, dividing progenitor cells. RORβ1-deficient mice lose expression of pancreas-specific transcription factor 1a (Ptf1a) but retain forkhead box n4 factor (Foxn4), two early-acting factors necessary for amacrine and horizontal cell generation. RORβ1 and Foxn4 synergistically induce Ptf1a expression, suggesting a central role for RORβ1 in a transcriptional hierarchy that directs this interneuron differentiation pathway. Moreover, ectopic RORβ1 expression in neonatal retina promotes amacrine cell differentiation.
orphan nuclear receptor; forkhead box transcription factor Foxn4; basic helix-loop-helix factor Ptf1a; neurogenesis; inhibitory interneuron
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.
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.
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.
Differently from prior studies, our review included updated Norrköping 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.
Prostatic neoplasm; Mass screening; Mortality; Prostate specific antigen; Review; Meta-analysis
Human papillomavirus (HPV) is a significant cause of cervical cancer-related deaths worldwide. Because HPV is a sexually transmitted mucosal pathogen, enhancement of antigen-specific mucosal immune response likely serves good strategy for vaccination. However, mucosal vaccines generally do not induce strong enough immune responses. Previously we proved that a bacterial flagellin, Vibrio vulnificus FlaB, induce strong antigen-specific immune responses by stimulating the Toll-like receptor 5. In this study, we tested whether FlaB could serve as an effective mucosal adjuvant for a peptide-based HPV preventive cancer vaccine.
Materials and Methods
Mice were intranasally administered with a mixture of FlaB and E6/E7 protective peptides in 5-day interval for a total of two times. Five-days after the last vaccination, cellular immune responses of the vaccinated mice were analyzed. Tumor growth was also observed after a subcutaneous implantation of TC-1 cells bearing E6/E7 antigens.
Intranasal administration of the E6/E7 peptide mixture with FlaB elicited a strong antigen-specific cytotoxic T lymphocyte activity and antigen-specific interferon-γ production from splenocytes and cervical lymph node cells. Furthermore, FlaB, as a mucosal adjuvant, conferred an excellent protection against TC-1 tumor challenge with high survival rates in E6/E7 immunized animals.
These results indicate that FlaB can be a promising mucosal adjuvant for nasal HPV vaccine development.
Flagellin; Adjuvant; Neoplasms; Vaccines
Countries with historically unlimited patient choice of medical provider, such as Korea, have been promoting rational health care pathways. Factors related to the length of doctor-patient relationship (DPR) for enhancing primary care in those countries should be studied. Participants were patients who had visited their family practices on six or more occasions over a period of more than 6 months. Five domains (21 items) of the Korean Primary Care Assessment Tool (first contact, coordination function, comprehensiveness, family/community orientation, and personalized care) and general questions were administered in the waiting rooms. From seven practices, the response rate was 83.7% (495/591). The older the age, the lower the income, the shorter the duration of education, the more the number of diseases the patients had, and in provincial cities rather than in Seoul, the longer length of DPR ( ≥ 4 yr) was shown. The long-term DPR was associated with total primary care quality score (upper [ ≥ 71.4] vs lower [ < 71.4], OR, 1.74; 95% CI, 1.10-2.76), especially with coordination function (OR, 1.01; 95% CI, 1.00-1.02), being adjusted for confounding variables. Strengthening the coordination function may have to be the first consideration in primary care policy in countries like Korea.
Primary Health Care; Quality Assurance; Health Care Policy; Korea
The objective of this study was to conduct the systematic evaluation of methodological quality of clinical practice guidelines (CPGs) in Korea. The authors conducted a very comprehensive literature search to identify potential CPGs for evaluation. CPGs were selected which were consistent with a predetermined criteria. Four reviewers evaluated the quality of the CPGs using the Appraisal of Guidelines, Research and Evaluation (AGREE) Instrument. AGREE item scores and standardized domain scores were calculated. The inter-rater reliability of each domain was evaluated using the intra-class correlation coefficient (ICC). Consequently, 66 CPGs were selected and their quality evaluated. ICCs for CPG appraisal using the AGREE Instrument ranged from 0.626 to 0.877. Except for the "Scope and Purpose" and "Clarity and Presentation domains", 80% of CPGs scored less than 40 in all other domains. This review shows that many Korean research groups and academic societies have made considerable efforts to develop CPGs, and the number of CPGs has increased over time. However, the quality of CPGs in Korea were not good according to the AGREE Instrument evaluation. Therefore, we should make more of an effort to ensure the high quality of CPGs.
Clinical Practice Guideline; Quality Improvement
We describe a patient with Churg-Strauss syndrome who developed unilateral anterior ischemic optic neuropathy. A 54-year-old man with a history of bronchial asthma, allergic rhinitis, and sinusitis presented with sudden decreased visual acuity in his right eye that had begun 2 weeks previously. The visual acuity of his right eye was 20 / 50. Ophthalmoscopic examination revealed a diffusely swollen right optic disc and splinter hemorrhages at its margin. Goldmann perimetry showed central scotomas in the right eye and fluorescein angiography showed remarkable hyperfluorescence of the right optic nerve head. Marked peripheral eosinphilia, extravascular eosinophils in a bronchial biopsy specimen, and an increased sedimentation rate supported the diagnosis of Churg-Strauss syndrome. Therapy with methylprednisolone corrected the laboratory abnormalities, improved clinical features, and preserved vision, except for the right central visual field defect. Early recognition of this systemic disease by ophthalmologists may help in preventing severe ocular complications.
Churg-Strauss syndrome; Ischemic optic neuropathy; Papilledema
Nail has been a substitute DNA source for genotyping. To investigate the integrity and consistency of nail DNA amplification for biomarker study, nail clippings from 12 subjects were collected at monthly intervals. The possibility of longer amplification and existence of GAPDH RNA/protein, were also investigated with three nail samples.
Three primer sets were designed for quantitative amplification of nuclear and mitochondrial genes and analysis of their consistency. The mean threshold cycles in amplification of the target genes were compared to test the consistency of polymerase chain reaction (PCR) performance among individual factors including age groups, sex, family, the nail source, and by the size of the amplification segments.
The amplification of the target genes from nail DNA showed similar integrity and consistency between the nail sources, and among the serial collections. However, nail DNA from those in their forties showed earlier threshold cycles in amplification than those in their teens or seventies. Mitochondrial DNA (mtDNA) showed better DNA integrity and consistency in amplification of all three targets than did nuclear DNA (nucDNA). Over 9 kb of mtDNA was successfully amplified, and nested quantitative PCR showed reliable copy numbers (%) between the two loci. Reverse transcription PCR for mRNA and immunoblotting for GAPDH protein successfully reflected their corresponding amounts. Regarding the existence of RNA and protein in nails, more effective extraction and detection methods need to be set up to validate the feasibility in biomarker study.
Nail DNA might be a feasible intra-individual monitoring biomarker. Considering integrity and consistency in target amplification, mtDNA would be a better target for biomarker research than nucDNA.
Biomarks in nail; Intra-individual monitoring; Circulatory DNA
Mucosal vaccination, capable of inducing protective immune responses both in the mucosal and systemic immune compartments, has many advantages and is regarded as a blue ocean in the vaccine industry. Mucosal vaccines can offer lower costs, better accessability, needle-free delivery, and higher capacity of mass immunizations during pandemics. However, only very limited number of mucosal vaccines was approved for human use in the market yet. Generally, induction of immune responses following mucosal immunization requires the co-administration of appropriate adjuvants that can initiate and support the effective collaboration between innate and adaptive immunity. Classically, adjuvant researches were rather empirical than keenly scientific. However, during last several years, fundamental scientific achievements in innate immunity have been translated into the development of new mucosal adjuvants. This review focuses on recent developments in the concepts of adjuvants and innate immunity, mucosal immunity with special interest of vaccine development, and basic and applied researches in mucosal adjuvant.
Mucosal; Vaccine; Adjuvant; Innate immunity
The cadherin family is classified into classical cadherins, desmosomal cadherins and protocadherins (PCDHs). Genomic structures distinguish between PCDHs and other cadherins, and between clustered and non-clustered PCDHs. The phylogenetic analysis with full sequences of non-clustered PCDHs enabled them to be further classified into three subgroups: δ1 (PCDH1, PCDH7, PCDH9, PCDH11 and PCDH20), δ2 (PCDH8, PCDH10, PCDH12, PCDH17, PCDH18 and PCDH19) and ε (PCDH15, PCDH16, PCDH21 and MUCDHL). ε-PCDH members except PCDH21 have either higher or lower numbers of cadherin repeats than those of other PCDHs. Non-clustered PCDHs are expressed predominantly in the nervous system and have spatiotemporally diverse expression patterns. Especially, the region-specific expressions of non-clustered PCDHs have been observed in cortical area of early postnatal stage and in caudate putaman and/or hippocampal formation of mature brains, suggesting that non-clustered PCDHs play roles in the circuit formation and maintenance. The non-clustered PCDHs appear to have homophilic/heterophilic cell-cell adhesion properties, and each member has diverse cell signaling partnership distinct from those of other members (PCDH7/TAF1; PCDH8/TAO2δ; PCDH10/Nap1; PCDH11/δ-catenin; PCDH18/mDab1). Furthermore, each PCDH has several isoforms with differential cytoplasmic sequences, suggesting that one PCDH isoform could activate intracellular signaling differential from other isoforms. These facts suggest that non-clustered PCDHs play roles as a mediator of a regulator of other molecules as well as cell-cell adhesion. Furthermore, some non-clustered PCDHs have been considered to be involved in neuronal diseases such as autism-spectrum disorders, schizophrenia and female-limited epilepsy and cognitive impairment, suggesting that they play multiple, tightly regulated roles in normal brain function. In addition, some non-clustered PCDHs have been suggested as candidate tumor suppressor genes in several tissues. Although molecular adhesive and regulatory properties of some PCDHs began to be unveiled, the endeavor to understand the molecular mechanism of non-clustered PCDH is still in its infancy and requires future study.
non-clustered protocadherins; gene structure; cell adhesion; intracellular signaling; neural disease; cancer