Diagnostic test accuracy: application and practice using R software

The objective of this paper is to describe general approaches of diagnostic test accuracy (DTA) that are available for the quantitative synthesis of data using R software. We conduct a DTA that summarizes statistics for univariate analysis and bivariate analysis. The package commands of R software were “metaprop” and “metabin” for sensitivity, specificity, and diagnostic odds ratio; forest for forest plot; reitsma of “mada” for a summarized receiver-operating characteristic (ROC) curve; and “metareg” for meta-regression analysis. The estimated total effect sizes, test for heterogeneity and moderator effect, and a summarized ROC curve are reported using R software. In particular, we focus on how to calculate the effect sizes of target studies in DTA. This study focuses on the practical methods of DTA rather than theoretical concepts for researchers whose fields of study were non-statistics related. By performing this study, we hope that many researchers will use R software to determine the DTA more easily, and that there will be greater interest in related research

Validation and Reliability of a Smartphone Application for the International Prostate Symptom Score Questionnaire: A Randomized Repeated Measures Crossover Study

Background: Smartphone-based assessment may be a useful diagnostic and monitoring tool for patients. There have been many attempts to create a smartphone diagnostic tool for clinical use in various medical fields but few have demonstrated scientific validity. Objective: The purpose of this study was to develop a smartphone application of the International Prostate Symptom Score (IPSS) and to demonstrate its validity and reliability. Methods: From June 2012 to May 2013, a total of 1581 male participants (>= 40 years old), with or without lower urinary tract symptoms (LUTS), visited our urology clinic via the health improvement center at Soonchunhyang University Hospital (Republic of Korea) and were enrolled in this study. A randomized repeated measures crossover design was employed using a smartphone application of the IPSS and the conventional paper form of the IPSS. Paired t test under a hypothesis of non-inferior trial was conducted. For the reliability test, the intraclass correlation coefficient (ICC) was measured. Results: The total score of the IPSS (P=.289) and each item of the IPSS (P=.157-1.000) showed no differences between the paper version and the smartphone version of the IPSS. The mild, moderate, and severe LUTS groups showed no differences between the two versions of the IPSS. A significant correlation was noted in the total group (ICC=.935, P<.001). The mild, moderate, and severe LUTS groups also showed significant correlations (ICC=.616,.549, and .548 respectively, all P<.001). There was selection bias in this study, as only participants who had smartphones could participate. Conclusions: The validity and reliability of the smartphone application version were comparable to the conventional paper version of the IPSS. The smartphone application of the IPSS could be an effective method for measuring lower urinary tract symptoms.X1144Ysciescopu

Evaluation of 28 Human Embryonic Stem Cell Lines for Use as Unrelated Donors in Stem Cell Therapy: Implications of HLA and ABO Genotypes

For human embryonic stem cells (hESCs) to be used clinically, it is imperative that immune responses evoked by hESCs and their derivates after transplantation should be prevented. Human leukocyte antigens (HLA) and ABO blood group antigens are important histocompatibility factors in graft rejection. HLA matching between recipient and unrelated donors, in particular, is important in improving outcomes in hematopoietic cell transplantation (HCT). We have established and successfully maintained 29 hESC lines and analyzed the HLA and ABO genotypes of these lines. HLA-A, -B, -C and -DR (DRB1) genotyping was performed by polymerase chain reaction (PCR) sequence-based typing and ABO genotyping was carried out by PCR restriction fragment length polymorphism methods. To determine what proportion of the Korean population would be covered by these cell lines in organ transplantation, 27 cell lines with HLA-A, -B, and -DR data were evaluated for HCT (cord blood) donors and 28 cell lines with HLA-DR and ABO data were evaluated for solid organ (kidney) transplantation donors, and then compared the data with those from 6,740 donated cord bloods. When <= 2 HLA mismatches are allowed for HCT, as currently accepted for cord blood transplantation, it was estimated that about 16% and 25% of the possible recipients can find one or more donor cell lines with mismatches at A, B, DRB1 allele level and at A, B antigen/DRB1 allele level, respectively. When HLA-DR antigen level matching and ABO compatibility was considered for solid organ (kidney) transplantation, it was estimated that about 29% and 96% of the possible recipients can find one or more ABO-compatible donor cell lines with 0 and 1 DR mismatches, respectively. We provided the first report on the HLA and ABO genotypes of hESC lines, and estimated the degree of HLA and ABO matching in organ transplantation for the Korean population.Yu JY, 2009, SCIENCE, V324, P797, DOI 10.1126/science.1172482Kaji K, 2009, NATURE, V458, P771, DOI 10.1038/nature07864Lee JY, 2010, FERTIL STERIL, V93, P976, DOI 10.1016/j.fertnstert.2008.10.017Holdsworth R, 2009, TISSUE ANTIGENS, V73, P95, DOI 10.1111/j.1399-0039.2008.01183.xLehec SC, 2009, CELL TRANSPLANT, V18, P941, DOI 10.3727/096368909X471323Oishi K, 2009, CELL TRANSPLANT, V18, P581Molne J, 2008, TRANSPLANTATION, V86, P1407, DOI 10.1097/TP.0b013e31818a6805Fernandes AM, 2010, CELL TRANSPLANT, V19, P509, DOI 10.3727/096368909X485067Stadtfeld M, 2008, SCIENCE, V322, P945, DOI 10.1126/science.1162494Wang GW, 2005, BIOCHEM BIOPH RES CO, V330, P934, DOI 10.1016/j.bbrc.2005.03.058Hoffman LM, 2005, NAT BIOTECHNOL, V23, P699, DOI 10.1038/nbt1102Li Y, 2005, BIOTECHNOL BIOENG, V91, P688, DOI 10.1002/bit.20536Vallier L, 2005, J CELL SCI, V118, P4495, DOI 10.1242/jcs.02553Taylor CJ, 2005, LANCET, V366, P2019Boyd AS, 2005, ADV DRUG DELIVER REV, V57, P1944, DOI 10.1016/j.addr.2005.08.004Ludwig TE, 2006, NAT BIOTECHNOL, V24, P185, DOI 10.1038/nbt1177Drukker M, 2006, STEM CELLS, V24, P221, DOI 10.1634/stemcells.2005-0188Priddle H, 2006, STEM CELLS, V24, P815, DOI 10.1634/stemcells.2005-0356Reubinoff BE, 2000, NAT BIOTECHNOL, V18, P399Amit M, 2000, DEV BIOL, V227, P271Xu CH, 2001, NAT BIOTECHNOL, V19, P971Drukker M, 2002, P NATL ACAD SCI USA, V99, P9864, DOI 10.1073/pnas.142298299Richards M, 2002, NAT BIOTECHNOL, V20, P933, DOI 10.1038/nbt726Bradley JA, 2002, NAT REV IMMUNOL, V2, P859, DOI 10.1038/nri934Amit M, 2003, BIOL REPROD, V68, P2150, DOI 10.1095/biolreprod.102.012583Li L, 2004, STEM CELLS, V22, P448Drukker M, 2004, TRENDS BIOTECHNOL, V22, P136, DOI 10.1016/j.tibtech.2004.01.003Thomson JA, 1998, SCIENCE, V282, P1145Petersdorf EW, 1999, CURR OPIN IMMUNOL, V11, P521Bodnar MS, 2004, STEM CELLS DEV, V13, P243Koivisto H, 2004, REPROD BIOMED ONLINE, V9, P330Rocha V, 2004, NEW ENGL J MED, V351, P2276Laughlin MJ, 2004, NEW ENGL J MED, V351, P2265Lee JB, 2005, BIOL REPROD, V72, P42, DOI 10.1095/biolrepod.104.033480Xu RH, 2005, NAT METHODS, V2, P185, DOI 10.1038/NMETH744Beattie GM, 2005, STEM CELLS, V23, P489, DOI 10.1634/stemcells.2004-0279Genbacev O, 2005, FERTIL STERIL, V83, P1517, DOI 10.1016/j.fertnstert.2005.01.086Oh SKW, 2006, CLIN EXP PHARMACOL P, V33, P489Skottman H, 2006, FEBS LETT, V580, P2875, DOI 10.1016/j.febslet.2006.03.083Xiao L, 2006, STEM CELLS, V24, P1476, DOI 10.1634/stemcells.2005-0299Stussi G, 2006, TRANSFUS APHER SCI, V35, P59, DOI 10.1016/j.transci.2006.05.009Takahashi K, 2006, CELL, V126, P663Guhr A, 2006, STEM CELLS, V24, P2187, DOI 10.1634/stemcells.2006-0053Klumpp TR, 2006, BONE MARROW TRANSPL, V38, P615, DOI 10.1038/sj.bmt.1705496Nakajima F, 2007, STEM CELLS, V25, P983, DOI 10.1634/stemcells.2006-0566Huangfu DW, 2008, NAT BIOTECHNOL, V26, P1269, DOI 10.1038/nbt.1502Petersdorf EW, 2008, CURR OPIN IMMUNOL, V20, P588, DOI 10.1016/j.coi.2008.06.014Chen YT, 2008, STEM CELLS DEV, V17, P853, DOI 10.1089/scd.2007.0226Park IH, 2008, CELL, V134, P877, DOI 10.1016/j.cell.2008.07.041Swijnenburg RJ, 2008, P NATL ACAD SCI USA, V105, P12991, DOI 10.1073/pnas.0805802105Unger C, 2008, HUM MOL GENET, V17, pR48, DOI 10.1093/hmg/ddn079Drukker M, 2008, SEMIN IMMUNOL, V20, P123, DOI 10.1016/j.smim.2007.11.002Revazova ES, 2008, CLONING STEM CELLS, V10, P11, DOI 10.1089/clo.2007.0063Mountford JC, 2008, TRANSFUSION MED, V18, P1, DOI 10.1111/j.1365-3148.2007.00807.xPark IH, 2008, NATURE, V451, P141, DOI 10.1038/nature06534Nakagawa M, 2008, NAT BIOTECHNOL, V26, P101, DOI 10.1038/nbt1374Buzzeo MP, 2008, CELL TRANSPLANT, V17, P489Kamani N, 2008, BIOL BLOOD MARROW TR, V14, P1, DOI 10.1016/j.bbmt.2007.11.003Saric T, 2008, CELLS TISSUES ORGANS, V188, P78, DOI 10.1159/000118784Navarro-Alvarez N, 2008, CELL TRANSPLANT, V17, P27KASTENBERG ZJ, 2008, TRANSPLANT REV ORLAN, V22, P215Lee SJ, 2007, BLOOD, V110, P4576, DOI 10.1182/blood-2007-06-097386Shaw BE, 2007, BLOOD, V110, P4560, DOI 10.1182/blood-2007-06-095265Strom S, 2007, HUM REPROD, V22, P3051, DOI 10.1093/humep/dem35Lin G, 2007, CELL RES, V17, P999, DOI 10.1038/cr.2007.97Crook JM, 2007, CELL STEM CELL, V1, P490Helming AM, 2007, PEDIATR BLOOD CANCER, V49, P313, DOI 10.1002/pbc.21025Cabrera CM, 2007, CELL BIOL INT, V31, P1072, DOI 10.1016/j.cellbi.2007.03.015Lei T, 2007, CELL RES, V17, P682, DOI 10.1038/cr.2007.61Okita K, 2007, NATURE, V448, P313, DOI 10.1038/nature05934Wernig M, 2007, NATURE, V448, P318, DOI 10.1038/nature05944Maherali N, 2007, CELL STEM CELL, V1, P55, DOI 10.1016/j.stem.2007.05.014Eapen M, 2007, LANCET, V369, P1947

Geographic Distribution of Urologists in Korea, 2007 to 2012

The adequacy of the urologist work force in Korea has never been investigated. This study investigated the geographic distribution of urologists in Korea. County level data from the National Health Insurance Service and National Statistical Office was analyzed in this ecological study. Urologist density was defined by the number of urologists per 100,000 individuals. National patterns of urologist density were mapped graphically at the county level using GIS software. To control the time sequence, regression analysis with fitted line plot was conducted. The difference of distribution of urologist density was analyzed by ANCOVA. Urologists density showed an uneven distribution according to county characteristics (metropolitan cities vs. nonmetropolitan cities vs. rural areas; mean square = 102.329, P < 0.001) and also according to year (mean square = 9.747, P = 0.048). Regression analysis between metropolitan and non-metropolitan cities showed significant difference in the change of urologists per year (P = 0.019). Metropolitan cities vs. rural areas and non-metropolitan cities vs. rural areas showed no differences. Among the factors, the presence of training hospitals was the affecting factor for the uneven distribution of urologist density (P < 0.001). Uneven distribution of urologists in Korea likely originated from the relatively low urologist density in rural areas. However, considering the time sequencing data from 2007 to 2012, there was a difference between the increase of urologist density in metropolitan and non-metropolitan cities.open1122sciescopuskc

Bladder Recovery by Stem Cell Based Cell Therapy in the Bladder Dysfunction Induced by Spinal Cord Injury: Systematic Review and Meta-Analysis

Background Bladder dysfunction induced by spinal cord injury (SCI) can become problematic and severely impair the quality of life. Preclinical studies of spinal cord injury have largely focused on the recovery of limb function while neglecting to investigate bladder recovery. Objective The present study was performed to investigate and review the effect of stem cell-based cell therapy on bladder recovery in SCI. Methods We conducted a meta-analysis of urodynamic findings of experimental trials that included studies of stem cell-based cell therapy in SCI. Relevant studies were searched using MEDLINE, EMBASE and Cochrane Library (January 1990 -December 2012). Final inclusion was determined by a urodynamic study involving detailed numerical values. Urodynamic parameters for analysis included voiding pressure, residual urine, bladder capacity and non-voiding contraction (NVC). Meta-analysis of the data, including findings from urodynamic studies, was performed using the Mantel-Haenszel method. Results A total of eight studies were included with a sample size of 224 subjects. The studies were divided into different subgroups by different models of SCI. After a stem cell-based cell therapy, voiding pressure (-6.35, p < 0.00001, I-2 = 77%), NVC (-3.58, p < 0.00001, I-2 = 82%), residual urine (-024, p = 0.004, I-2 = 95%) showed overall significant improvement. Bladder capacity showed improvement after treatment only in the transection type (-0.23, p = 0.0002, I-2 = 0%). Conclusion After stem cell-based cell therapy in SCI, partial bladder recovery including improvement of voiding pressure, NVC, and residual urine was demonstrated. Additional studies are needed to confirm the detailed mechanism and to obtain an ideal treatment strategy for bladder recovery.open1156sciescopu

The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer:A Systematic Review and Meta-analysis of Prospective Studies

CONTEXT: Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies.OBJECTIVE: To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients.EVIDENCE ACQUISITION: We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators.EVIDENCE SYNTHESIS: We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively.CONCLUSIONS: MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain.PATIENT SUMMARY: Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.</p

The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer:A Systematic Review and Meta-analysis of Prospective Studies

CONTEXT: Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies.OBJECTIVE: To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients.EVIDENCE ACQUISITION: We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators.EVIDENCE SYNTHESIS: We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively.CONCLUSIONS: MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain.PATIENT SUMMARY: Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.</p

Meta-analysis of diagnostic test accuracy studies with multiple thresholds for data integration

OBJECTIVES The objective of this study is to introduce methods to use all of the information without omission when individual studies provide multiple effect sizes according to multiple cut-off values (thresholds) during diagnostic test accuracy (DTA) for data integration. For diagnostic test meta-analysis, a general performance method for synthesizing data according to one cut value in one study and a performance method for synthesizing data according to two or more cut values in one study were compared and analyzed. METHODS As sample data for meta-analysis of DTA studies, 13 DTA studies on prostate cancer (34 effect sizes including total cut-offs) were collected. The summary statistics were calculated and the summary line was analyzed using the “meta”, “mada”, and “diagmeta” packagesof the R software. RESULTS The summary statistics of the random effect model univariate analysis of the “meta” package with a single cut-off corresponding to the highest Youden index in a single study and those of the bivariate analysis of the “mada” package were highly similar. However, in the bivariate analysis of the “diagmeta” package including all cut-off values, the sensitivity decreased and the specificity increased as the amount of data increased. CONCLUSIONS Considering the heterogeneity of the summary receiver op erating characteristic curve and the use of all given cut-offs, the use of the bivariate analysis model of the “diagmeta” package is recommended. This study focused on practical methods of DTA rather than theoretical concepts for use by researchers whose fields of study are non-statistics related. By performing this study, we hope that many researchers will use R software to determine the DTA more easily, and that there will be greater interest in related research