DOI： 10.1111/cas.14149

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/14397595.2018.1494501

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DOI： 10.21037/jtd.2019.05.76

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/14397595.2018.1457424

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/14397595.2019.1649103

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記述言語：日本語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier B.V.  

DOI： 10.1016/j.jiac.2017.12.009

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DOI： 10.1111/ajco.12837

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/rheumatology/kex036

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Internal Medicine  

Objective This retrospective cohort study investigated whether the three components of the blood cell count have prognostic implications in HIV-negative Japanese adult inpatients with smear-positive pulmonary tuberculosis. Methods We reviewed patients who were treated by the isoniazid, rifampicin, pyrazinamide, and ethambutol regimen or by the isoniazid, rifampicin, and ethambutol regimen. The association between the patient data on admission and the survival outcome was evaluated. Results We reviewed 367 consecutive patients (male, 60.5%) with a median age of 72 [interquartile range (IQR), 54-82] years. While the white blood cell count did not differ between the two groups, (discharged alive: 7,000/μL
IQR, 5,500-9,300
died in hospital: 7,200/μL
IQR, 5,600-9,400
p=0.797), hemoglobin level (discharged alive: 11.5 g/dL
IQR, 10.0-13.1
died in hospital: 9.9 g/dL
IQR, 8.6-11.3
p&lt
0.001) and the platelet count (discharged alive: 275,000/μL
IQR, 206,000-345,000
died in hospital: 149,000/μL
IQR, 93,000-236,000
p&lt
0.001) were lower in patients who died in hospital. After dividing patients into hemoglobin- and platelet-based quantiles, the lower quantile class tended to show poorer survival (log-rank test for trend p&lt
0.001 for both). A multi-variable Cox proportional hazards model revealed that hazard ratio for in-hospital death for every 1,000/μL increase of platelet count was 0.997 (95%CI, 0.995-0.999
p=0.010)
the hazard ratio for the hemoglobin level was not significant. Conclusion A low platelet count was clearly related to a poor life prognosis in HIV-negative Japanese adult inpatients with smear-positive pulmonary tuberculosis.

DOI： 10.2169/internalmedicine.0138-17

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-017-09938-z

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記述言語：英語   出版者・発行元：ELSEVIER SCI LTD  

Objectives: We aimed to assess diagnostic test accuracy of antigenaemia assay for PCR-proven cytomegalovirus (CMV) infection.
Methods: We systematically searched studies that provide data both on sensitivity and specificity of the CMV antigenaemia assay using the PCR as the reference standard. Adults, children, infants, individuals who were immunocompromised for any reason, symptomatic patients and asymptomatic individuals were all included. A hierarchical summary receiver operating characteristics model was used for diagnostic meta-analysis. Study quality was assessed by Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies. Protocol registration identification is CRD42016035892.
Results: We identified 75 eligible articles including 9058 CMV PCR-positive individuals and 22 232 PCR-negative individuals. The diagnostic odds ratio for positive antigenaemia was 30 (95% CI 24-38, I-2 = 28%) and the area under the hierarchical summary receiver operating characteristic curve was 0.86 (95% CI 0.83-0.88). The summary estimates of sensitivity and specificity were 0.65 (95% CI 0.59- 0.70) and 0.94 (95% CI 0.93-0.95), respectively. The positive likelihood ratio of 10.9 (95% CI 8.5-14.0) suggested that a positive result from the antigenaemia assay greatly increased the probability of PCR-proven CMV infection, but a negative likelihood ratio of 0.38 (95% CI 0.32-0.44) indicated that a negative result led to a small decrease in the probability of PCR-proven CMV infection. Sensitivity and subgroup analyses replicated these results.
Conclusions: The antigenaemia assay overlooked 35% of PCR-proven CMV infections; hence, a negative result of an antigenaemia assay could not rule out a CMV infection. (C) 2017 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.

DOI： 10.1016/j.cmi.2017.05.009

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記述言語：英語  

DOI： 10.1001/jama.2017.11903

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Platinum regimens still play a key role in chemotherapy for incurable non-small cell lung cancer (NSCLC). Although guidelines list many platina regimens, the best regimens have not yet clarified. Electronic searches were carried out during November 26th-28th, 2016. We included individually randomized trials comparing two or more platinum regimes for incurable chemo-naive NSCLC published in English full papers. The platinum doublets should be either Cisplatin (CDDP), Carboplatin (CBDCA), or Nedaplatin (CDGP) plus one of the third-generation agents. The platinum triplet should be the doublet plus bevacizumab (BEV). The data were independently extracted and cross-checked by two investigators. We did not observed heterogeneity (whole network level Q = 28.9, df = 34, P = 0.717) among 59 pairwise comparisons from 45 studies with 16141 cases for the primary outcome, hazard ratio for overall survival (HRos). Using CBDCA + Paclitaxel (PTX) + BEV as a common comparator, CDGP + Docetaxel (DTX) (HRos = 0.98, 95% CI: 0.75-1.29, P = 0.884), CDDP + Tegafur gimeracil oteracil (S1) (HRos = 1.23, 95% CI: 0.96-1.57, P = 0.099), CBDCA + S1 (HRos = 1.23, 95% CI: 0.99-1.53, P = 0.062), and CDGP + Gemcitabine (GEM) (HRos = 1.24, 95% CI: 0.71-2.17, P = 0.45) did not have significantly poorer HRos. We suggest that these regimens as acceptable first-choice regimens.

DOI： 10.1038/s41598-017-13724-2

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記述言語：英語  

DOI： 10.1016/j.cmi.2017.03.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

IntroductionNo previous study clearly demonstrated the association between the absolute neutrophil count (ANC) nadir and the absolute monocyte count (AMC) nadir among patients undergoing chemotherapy.
MethodsWe retrospectively reviewed patients with an incurable lung cancer in two university hospital who were treated with platinum doublet or triplet. In this study, the nadir was defined as the lowest value during days 1-22.
ResultsWe observed 75 patients: 61 men (81%) and 14 women (19%), median age of 69 years. The number of days that elapsed between the first day of chemotherapy and the median ANC nadir of 12 days was longer than that for AMC nadir of 6 (Wilcoxon signed rank test: P<0.001). The number of days that elapsed between the first day of chemotherapy and the AMC nadir was the only factor that had a significant correlation with that for ANC nadir (Spearman's rank correlation: r=0.34, P=0.003). Among 75 patients, 23 (31%) had an ANC at nadir <1000/L. AMC at nadir of 100/L predicted an ANC at nadir <1000/L with a sensitivity of 83% and a specificity of 56%.
ConclusionBoth neutrophils and monocytes are differentiated from a common progenitor, a granulocyte macrophage colony forming cell, which can provide good explanation for the association between ANC and AMC nadirs. We would like to recommend physicians to observe the AMC nadir to predict the timing and severity of the ANC nadir.

DOI： 10.1111/crj.12358

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To assess the accuracy of ultrasound measurements of fetal biometric parameters for prenatal diagnosis of microcephaly in the context of Zika virus (ZIKV) infection, we searched bibliographic databases for studies published until March 3rd, 2016. We extracted the numbers of true positives, false positives, true negatives, and false negatives and performed a meta-analysis to estimate group sensitivity and specificity. Predictive values for ZIKV-infected pregnancies were extrapolated from those obtained for pregnancies unrelated to ZIKV. Of 111 eligible full texts, nine studies met our inclusion criteria. Pooled estimates from two studies showed that at 3, 4 and 5 standard deviations (SDs) <mean, sensitivities were 84%, 68% and 58% for head circumference (HC); 76%, 58% and 58% for occipitofrontal diameter (OFD); and 94%, 85% and 59% for biparietal diameter (BPD). Specificities at 3, 4 and 5 SDs below the mean were 70%, 91% and 97% for HC; 84%, 97% and 97% for OFD; and 16%, 46% and 80% for BPD. No study including ZIKV-infected pregnant women was identified. OFD and HC were more consistent in specificity and sensitivity at lower thresholds compared to higher thresholds. Therefore, prenatal ultrasound appears more accurate in detecting the absence of microcephaly than its presence.

DOI： 10.1038/s41598-017-01991-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

We conducted a single-center retrospective cohort study to evaluate whether the HbA1c level on admission could predict the in-hospital treatment outcome of smear-positive non-multi-drug-resistant HIV-negative culture-proven pulmonary tuberculosis inpatients. Our standard regimens under the direct observation were HRZE or HRE for the first two months followed by combination therapy with isoniazid and rifampicin. Our cohort consisted of consecutive 239 patients consisted of 147 men and 92 women with a median age of 73 years. The HbA1c level of patients whose HbA1c was above 7.0% on admission showed clear declining trends after admission. HbA1c on admission had no Spearman's rank correlation with time to discharge alive (r = 0.17) and time to becoming non-infective (r = 0.17). By Kaplan-Meier curves and a log-rank trend test, HbA1c quartile subgroups showed no association with times to discharge alive (p = 0.431), becoming non-infective (p = 0.113), and in-hospital death (p = 0.427). Based on multi-variate Cox analysis, HbA1c on admission had no significant impact on time to discharge alive (hazard ratio = 1.03, 95% CI 0.89-1.20, p = 0.659), becoming non-infective (hazard ratio = 0.93, 95% CI 0.80-1.06, p = 0.277), and in-hospital death (hazard ratio = 0.68, 0.43-1.07, p = 0.097). In conclusion, the HbA1c level on admission did not seem to affect in-hospital tuberculosis treatment outcomes in Japanese cohort.

DOI： 10.1038/srep46488

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記述言語：英語   出版者・発行元：AMER THORACIC SOC  

DOI： 10.1186/s12931-018-0852-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/rheumatology/kex285

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記述言語：英語   出版者・発行元：WILEY  

Background
Three classes of inhaler medications are used to manage chronic obstructive pulmonary disease (COPD): long-acting beta-agonists (LABA), long-acting muscarinic antagonists (LAMA), and inhaled corticosteroids (ICS). When two classes of medications are required, LAMA plus LABA (LAMA+LABA) and LABA plus ICS (LABA+ICS) are often selected because these combinations can be administered via a single medication device. The previous Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidance recommended LABA+ICS as the first-line treatment for managing stable COPD in high-risk people of categories C and D. However, the updated GOLD 2017 guidance recommends LAMA+LABA over LABA+ICS.
Objectives
To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD.
Search methods
We performed an electronic search of the Cochrane Airways Group Specialised Register (2 February 2016), ClinicalTrials.gov (4 June 2016), and the World Health Organization Clinical Trials Search Portal (4 June 2016), followed by a handsearch (5 June 2016). Two review authors screened and scrutinised the selected articles.
Selection criteria
We included individual randomised controlled trials, parallel-group trials, and cross-over trials comparing LAMA+LABA and LABA+ICS for stable COPD. The minimum accepted trial duration was one month and trials should have been conducted in an outpatient setting.
Data collection and analysis
Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (OR), and continuous data as mean differences (MD), with 95% confidence interval (CI) using Review Manager 5. Exacerbations were measured by counting the number of people experiencing one or more exacerbation.
Main results
We included 11 studies comprising 9839 participants in our quantitative analysis. Most studies included people with moderate to severe COPD, without recent exacerbations. One pharmaceutical sponsored trial that included only people with recent exacerbations was the largest study and accounted for 37% of participants. All but one study were sponsored by pharmaceutical companies, thus we rated them as having a high risk of 'other bias'. The unsponsored study was at high risk of performance and detection bias, and possible selective reporting.
Five studies recruited GOLD Category B participants, one study recruited Category D participants, two studies recruited Category A/B participants, and three studies recruited participants regardless of category. Follow-up ranged from 6 to 52 weeks.
Compared to the LABA+ICS arm, the results for the pooled primary outcomes for the LAMA+LABA arm were as follows: exacerbations, OR 0.82 (95% CI 0.70 to 0.96, P = 0.01, I-2 = 17%, low quality evidence); serious adverse events (SAE), OR 0.91 (95% CI 0.79 to 1.05, P = 0.18, I-2 = 0, moderate quality evidence); St. George's Respiratory Questionnaire (SGRQ) total score change from the baseline, MD -1.22 (95% CI -2.52 to 0.07, P = 0.06, I-2 = 71%, low quality evidence); and trough forced expiratory volume in one second (FEV1) change from the baseline, MD 0.08 L (95% CI 0.06 to 0.09, P &lt; 0.0001, I-2 = 50%, moderate quality evidence). Compared to the LABA+ICS arm, the results for the pooled secondary outcomes for the LAMA+LABA arm were as follows: pneumonia, OR 0.57 (95% CI 0.42 to 0.79, P = 0.0006, I-2 = 0%, low quality evidence); all-cause death, OR 1.01 (95% CI 0.61 to 1.67, P = 0.88, I-2 = 0%, low quality evidence); and SGRQ total score change from the baseline of 4 points or greater (the minimal clinically important difference for the SGRQ is 4 points), OR 1.25 (95% CI 1.09 to 1.44, P = 0.002, I-2 = 0%, moderate quality evidence).
Authors' conclusions
For the treatment of COPD, LAMA+LABA has fewer exacerbations, a larger improvement of FEV1, a lower risk of pneumonia, and more frequent improvement in quality of life as measured by an increase over 4 units or more of the SGRQ. These data were supported by low or moderate quality evidence generated from mainly participants with moderate to severe COPD in heterogeneous trials with an observation period of less than one year. Our findings support the recently updated GOLD guidance.

DOI： 10.1002/14651858.CD012066.pub2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective Onodera's Prognostic Nutritional Index (PNI), determined as "10x albumin (g/dL) + 0.005x lymphocyte count (/mu L)," was originally designed to determine the risk of complications following gastrointestinal surgery. This single-center, retrospective observational study was designed to investigate whether or not the PNI can predict the treatment outcome.
Methods We consecutively reviewed HIV-negative pulmonary tuberculosis adults in an isolation ward. Most patients were being treated with standard three-or four-drug regimens. Patients were discharged after consecutive negative smears/cultures were confirmed. The risk of all-cause death was assessed using a multivariable Cox proportional hazard model and a log-rank trend test.
Results During the observation period, we observed 371 consecutive patients with a median age of 72 (interquartile range [IQR]: 54-82) years. In our cohort, 295 (79.5%) patients were discharged alive, and 76 (20.5%) died in-hospital. Patients who died in-hospital had a lower PNI [median 21.2 (IQR: 18.5-25.9)] than those who were discharged alive [median 35.1 (IQR: 28.0-43.3); p&lt;0.001]. The area under the receiver operating characteristic curve was 0.87. After dividing the patients based on the baseline PNI quartile, those patients with a lower PNI showed a poorer survival than those with a higher PNI (log-rank trend p&lt;0.001). After adjusting for other baseline variables, the baseline PNI was still associated with in-hospital death with a hazard ratio of 0.86 (95% confidence interval: 0.82-0.91, p&lt;0.001).
Conclusion Our results showed that a low PNI was clearly related to a poor survival prognosis in smearpositive HIV-negative pulmonary tuberculosis inpatients.

DOI： 10.2169/internalmedicine.9120-17

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

Diagnostic test accuracy of the loop-mediated isothermal amplification (LAMP) assay for culture proven tuberculosis is unclear. We searched electronic databases for both cohort and case-control studies that provided data to calculate sensitivity and specificity. The index test was any LAMP assay including both commercialized kits and in-house assays. Culture-proven M. tuberculosis was considered a positive reference test. We included 26 studies on 9330 sputum samples and one study on 315 extra-pulmonary specimens. For sputum samples, 26 studies yielded the summary estimates of sensitivity of 89.6% (95% CI 85.6-92.6%), specificity of 94.0% (95% CI 91.0-96.1%), and a diagnostic odds ratio of 145 (95% CI 93-226). Nine studies focusing on Loopamp MTBC yielded the summary estimates of sensitivity of 80.9% (95% CI 76.0-85.1%) and specificity of 96.5% (95% CI 94.7-97.7%). Loopamp MTBC had higher sensitivity and lower specificity for smear-positive sputa compared to smear-negative sputa. In-house assays showed higher sensitivity and lower specificity compared to Loopamp MTBC. LAMP promises to be a useful test for the diagnosis of TB, however there is still need to improve the assay to make it simpler, cheaper and more efficient to make it competitive against other PCR methods already available.

DOI： 10.1038/srep39090

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.21037/jtd.2016.12.03

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier B.V.  

To clarify the functional changes after hospitalization due to pneumonia in elderly Japanese patients, we investigated the changes in physical functioning, nutritional routes, and diet that occurred after hospitalization in patients with nursing and healthcare-associated pneumonia (NHCAP). We analyzed 405 patients with NHCAP and compared findings with 448 patients with community-acquired pneumonia (CAP). Among the NHCAP patients, 140 (34%) patients showed a decline in activities of daily living function between baseline and discharge. After hospital discharge, 149 (37%) NHCAP patients did not return to the same residence location compared with where they were living prior to hospital admission. The frequency of this outcome was significantly higher in NHCAP patients than in CAP patients (p &lt
 0.0001). After 6 months' follow-up, of the patients who transferred to different hospitals, 41 (73%) patients with CAP had returned to their own home, but only 16 (20%) patients with NHCAP could return home (p &lt
 0.0001). Rates of alteration of nutritional route and type of diet from oral nutrition were significantly higher in NHCAP patients compared with CAP patients (22% vs 4%, p &lt
 0.0001). Our results demonstrated that approximately one-third of hospitalized patients with NHCAP showed a decline in physical function. In addition, approximately one-fifth of NHCAP patients had changed their route of nutrition and type of diet. Our results indicated that physicians should attach greater importance to preventative measures against NHCAP rather than relying on antibiotic therapy post-infection in the management of pneumonia in elderly patients in order to extend their healthy life expectancy.

DOI： 10.1016/j.jiac.2016.06.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

It is unclear whether in the treatment of community-acquired pneumonia (CAP) beta-lactam plus macrolide antibiotics lead to better survival than beta-lactam alone. We report a systematic review and meta-analysis. Trials and observational studies published in English were included, if they provided sufficient data on odds ratio for all-cause mortality for a beta-lactam plus macrolide regimen compared with beta-lactam alone. Two investigators independently searched for eligible articles. Of 514 articles screened, 14 were included: two open-label randomized controlled trials (RCTs) comprising 1975 patients, one non-RCT interventional study comprising 1011 patients and 11 observational studies comprising 33 332 patients. Random-model meta-analysis yielded an odds ratio for all-cause death for beta-lactam plus macrolide compared with beta-lactam alone of 0.80 (95% CI 0.69-0.92, P = 0.002) with substantial heterogeneity (I(2)  = 59%, P for heterogeneity = 0.002). Severity-based subgroup analysis and meta-regression revealed that adding macrolide had a favourable effect on mortality only for severe CAP. Of the two RCTs, one suggested that macrolide plus beta-lactam lead to better outcome compared with beta-lactam alone, while the other did not. Subgrouping based on study design, that is, RCT versus non-RCT, which was almost identical to subgrouping based on severity, revealed substantial inter-subgroup heterogeneity. Compared with beta-lactam alone, beta-lactam plus macrolide may decrease all-cause death only for severe CAP. However, this conclusion is tentative because this was based mainly on observational studies.

DOI： 10.1111/resp.12835

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

Currently, an anti-glycopeptidolipid (GPL)-core IgA antibody assay kit for diagnosing Mycobacterium avium complex (MAC) is commercially available. We conducted this systematic review and meta-analysis to reveal the precise diagnostic accuracy of anti-GPL-core IgA antibodies for MAC pulmonary disease (MAC-PD). We systematically searched reports that could provide data for both sensitivity and specificity by anti-GPL-core IgA antibody for clinically diagnosed MAC-PD. Diagnostic test accuracy was estimated using the bivariate model. Of the 257 articles that we had found through primary search, we finally included 16 reports consisted of 1098 reference positive subjects and 2270 reference negative subjects. The diagnostic odds ratio was 24.8 (95% CI 11.6-52.8, I2 = 5.5%) and the area under the hierarchical summary receiver operating characteristic curves was 0.873 (95% CI 0.837-0.913). With a cutoff value of 0.7 U/mL, the summary estimates of sensitivity and specificity were 0.696 (95% CI 0.621-0.761) and 0.906 (95% CI 0.836-0.951), respectively. The positive and negative likelihood ratios were 7.4 (95% CI 4.1-13.8) and 0.34 (95% CI 0.26-0.43), respectively. The demanding clinical diagnostic criteria may be a cause of false positive of the index test. The index test had good overall diagnostic accuracy and was useful to ruling in MAC-PD with the cutoff value.

DOI： 10.1038/srep29325

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Churchill Livingstone  

Nucleic acid amplification tests are a major diagnostic tool for pulmonary tuberculosis (PTB). Recently, digital PCR (dPCR) assay has improved sensitivity for the detection of small copy numbers of target molecules. The aim of this study is to explore the utility of dPCR for detecting Mycobacterium tuberculosis (MTB) DNA in PTB patient plasma. Total DNA was purified from plasma samples of newly diagnosed sputum smear-positive PTB patients. Copy numbers of MTB-specific genes in the samples were quantified with dPCR assays targeted for IS6110 or gyrB. A total of 33 PTB patients were enrolled. Significant differences between PTB patients and controls were observed in copy numbers of both targets: IS6110 mean ± SD, 144.8 ± 538.3 vs 0.44 ± 0.49 (copies/20 μL, p = 0.004
Mann-Whitney U test) and gyrB mean ± SD, 359.0 ± 2116 vs 0.07 ± 0.28 (copies/20 μL, p = 0.011
Mann-Whitney U test), respectively. This test had sensitivities of 65% or 29% and a specificity of 93% or 100% with the IS6110-targeted or gyrB-targeted assays, respectively. A dPCR assay successfully detected MTB DNA in PTB patient plasma. This minimally invasive and accurate method has potential to become an alternative diagnostic option.

DOI： 10.1016/j.tube.2016.04.004

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記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

We performed this systematic review and meta-analysis to assess the diagnostic accuracy of detecting glutamate dehydrogenase (GDH) for Clostridium difficile infection (CDI) based on the hierarchical model. Two investigators electrically searched four databases. Reference tests were stool cell cytotoxicity neutralization assay (CCNA) and stool toxigenic culture (TC). To assess the overall accuracy, we calculated the diagnostic odds ratio (DOR) using a DerSimonian-Laird random-model and area the under hierarchical summary receiver operating characteristics (AUC) using Holling's proportional hazard models. The summary estimate of the sensitivity and the specificity were obtained using the bivariate model. According to 42 reports consisting of 3055 reference positive comparisons, and 26188 reference negative comparisons, the DOR was 115 (95% CI: 77-172, I-2 = 12.0%) and the AUC was 0.970 (95% CI: 0.958-0.982). The summary estimate of sensitivity and specificity were 0.911 (95% CI: 0.871-0.940) and 0.912 (95% CI: 0.892-0.928). The positive and negative likelihood ratios were 10.4 (95% CI 8.4-12.7) and 0.098 (95% CI 0.066-0.142), respectively. Detecting GDH for the diagnosis of CDI had both high sensitivity and specificity. Considering its low cost and prevalence, it is appropriate for a screening test for CDI.

DOI： 10.1038/srep29754

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記述言語：英語  

DOI： 10.1038/srep26893

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記述言語：スペイン語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Doyma  

Background: Theophylline has been shown to improve respiratory function and oxygenation in patients with chronic obstruction pulmonary disease (COPD). However, the impact of theophylline on mortality in COPD patients has not been not sufficiently evaluated. Method: Two investigators independently searched for eligible articles in 4 databases. The eligibility criterion for this meta-analysis was an original research article that provided a hazard ratio for theophylline for all-cause mortality of COPD patients. Both randomized controlled trials and observational studies were accepted. After we confirmed no substantial heterogeneity (I2 &lt
50%), the fixed-model method with generic inverse variance was used for meta-analysis to estimate the pooled hazard ratio. Results: We screened 364 potentially eligible articles. Of the 364 articles, 259 were excluded on the basis of title and abstract, and 99 were excluded after examination of the full text. Our final analysis included 6 observational studies and no randomized controlled trials. One study reported 2 cohorts. The number of patients in each cohort ranged from 47 to 46,403. Heterogeneity (I2 = 42%, P = .11) and publication bias (Begg's test r = 0.21, P = .662) were not substantial. Fixed-model meta-analysis yielded a pooled hazard ratio for theophylline for all-cause death of 1.07 (95% confidence interval: 1.02-1.13, P = .003). Conclusion: This meta-analysis of 7 observational cohorts suggests that theophylline slightly increases all-cause death in COPD patients.

DOI： 10.1016/j.arbr.2015.06.014

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記述言語：英語   出版者・発行元：AMER COLL CHEST PHYSICIANS  

DOI： 10.1016/j.chest.2015.11.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

The A-DROP scoring system was originally designed to assess clinical severity of community acquired pneumonia using the following parameters: advanced Age, Dehydration, Respiratory failure, Orientation disturbance (confusion)
and, low blood Pressure. Total A-DROP score ranges zero to five assigning one point for each component, wherein five indicates the poorest prognosis. The purpose of this single-center retrospective study was to determine whether A-DROP could predict the risk for death in patients with pulmonary tuberculosis. We reviewed consecutive HIV-negative, non-multidrug-resistant smear-positive adult pulmonary tuberculosis patients. The cohort consisted of 134 men (38.8%), 211 women (61.2%), 272 who discharged alive (28.8%), and 73 who died in-hospital (21.2%) with a median age of 72 (IQR: 54-82) years. A one-point increase in the A-DROP score was associated with a higher risk for in-hospital mortality with odds ratio of 3.8 (95% confidence interval 2.8-5.2, P &lt
0.001). The area under receiver operating characteristics curve was 0.86. The total score cutoff of 1.5 provided the best Youden Index of 0.61. Using this criteria, total score &gt
1.5, sensitivity was 85% and specificity was 76%. Kaplan-Meier curve clearly indicated that in-hospital mortality increased with higher A-DROP scores (Log-rank test &lt
0.001). In conclusion, A-DROP score clearly indicate pulmonary tuberculosis in-hospital mortality.

DOI： 10.1038/srep21610

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six-, and nine-month progression-free survival were 63% (95% CI 57-69%, I2 =53%), 28% (95% CI 21-35%, I2 =71%), and 10% (95% CI 6-14%, I2 =41%), respectively. The pooled six-, 12-, and 18-month overall survival were 69% (95% CI 61-78%, I2 =83%), 36% (95% CI 28-44%, I2 =80%), and 15% (95% CI 8-21%, I2 =81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%.

DOI： 10.1038/srep18999

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PALACKY UNIV  

Background. The evaluation of chronic obstructive pulmonary disease (COPD) has been shifting from spirometry to focus on the patients' overall health. Despite the existence of many COPD prognostic scales, there remains a large gap for improvement, in particular a scale that incorporates the current focus on overall health. Methods. We proposed a new prognostic scale (the COPD Prognostic Score) through discussion among the authors based on published studies. Validation was retrospective, using data from the National Emphysema Treatment Trial. Results. The scores ranged from 0-16, where 16 indicated the poorest prognosis. We assigned 4 points each for forced expiratory volume in one second (%predicted), the modified Medical Research Council dyspnea scale, and age
2 points for the hemoglobin level
and one point each for decreased activity and respiratory emergency admission in the last two years. The validation cohort included 607 patients and consisted of 388 men (73.9%) and 219 women (36.1%), mean age 67 ± 6 years and an average forced expiratory volume in one second (% predicted) of 27 ± 7%. A one-point increase in the score was associated with increased all-cause death, with a hazard ratio of 1.28 (95%CI: 1.21-1.36. P &lt
0.001). The areas under the receiver operating characteristic curves for two-year and five-year all-cause death for the new scale were 0.72 and 0.66, respectively. These values were higher than those given by the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index and age, dyspnea, airway obstruction (ADO) index. Conclusion. The preliminary validation for a new COPD prognostic scale: the COPD Prognostic Score was developed with promising results thus far. Above mentioned 16-point score accurately predicted 2-year and 5-year all-cause mortality among subjects who suffered from severe and very severe COPD.

DOI： 10.5507/bp.2016.030

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記述言語：英語  

DOI： 10.1016/j.jtho.2016.04.025

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記述言語：英語  

Since 2010, studies on the diagnostic accuracy of COBAS TaqMan MTB (CTM) have been frequently reported with an unignorable discrepancy. The key inclusion criterion for this systematic review was original studies that could provide sufficient data for calculating the sensitivity and the specificity of CTM for M tuberculosis (TB) or M tuberculosis complex. The reference test was Mycobacterium culture. We used bivariate model for meta-analyses. Of the 201 candidate articles, we finally identified 17 eligible articles.Concerning the respiratory specimens, 1900 culture positive specimens and 20983 culture negative specimens from 15 studies were assessed. This provided the summary estimate sensitivity of 0.808 (95% CI 0.758-0.850) and the summary estimate specificity of 0.990 (95% CI 0.981-0.994). The area under curve was 0.956. The diagnostic odds ratio was 459 (95% CI 261-805, I(2) 26%). For the smear positive respiratory specimens, the sensitivity was 0.952 (95% CI 0.926-0.969) and the specificity was 0.916 (95% CI 0.797-0.968). For the smear negative respiratory specimens, the sensitivity and the specificity were 0.600 (95% CI 0.459-0.726) and 0.989 (95% CI 0.981-0.993), respectively. The diagnostic accuracy was poorer for the non-respiratory specimens, than for the respiratory specimens, but was acceptable. We believe that the information obtained from this study will aid physicians' decision making.

DOI： 10.1038/srep18113

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記述言語：英語  

DOI： 10.1111/resp.12603

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Internal Medicine  

Objective In the 1950s, a high-dose (40-70 mg/kg/day) of pyrazinamide (PZA), was reported to cause drug-induced liver injury (DILI) at an unacceptable frequency. It remains unclear whether adding PZA (Z) at the currently accepted low-dose (20-25 mg/kg/day) for two months to a regimen of isoniazid (H) + rifampicin (R) + ethambutol (E) actually increases the risk of DILI. Method Smear-positive tuberculosis patients were treated with daily HRE or HRZE regimen under direct observation. We used three independent models. Model 1 was analyzed with a multivariate Cox-analysis using a pre-matched cohort. Next, propensity score matching was conducted using the nearest neighbor method with caliper of 0.03. Models 2 and 3 were analyzed by univariate and multivariate Cox-analyses, respectively, with the matched cohort. DILI was assessed based on the guidelines of the American Thoracic Society. Results We reviewed the records of 383 patents (male, n=260
female n=123
mean age, 64±20 years). Among these patients, 75 patients were treated with HRE and 308 were treated with HRZE. DILI occurred in the first two months in 24% (18/75) and 8% (24/308) of the HRE-treated and HRZE-treated cases, respectively. In all three of the models, DILI was less frequent in patients treated with the HRZE regimen: Model 1, HR of 0.30 (95% confidence interval (CI) 0.14-0.68, p=0.004)
Model 2, HR of 0.37 (95%CI 0.14-0.96, p=0.041)
and Model 3, HR of 0.34 (95%CI 0.12-0.94, p=0.038). Conclusion The addition of the currently accepted low dose (20-25 mg/kg/day) of PZA to the HRE regimen did not increase the incidence of DILI during the first two months of treatment.

DOI： 10.2169/internalmedicine.54.5533

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa Healthcare  

Background: The minimum clinically important difference (MCID) for diffusing capacity of the lungs for carbon monoxide (DLCO) has not yet been solidly established. Methods: We used the dataset of surgical cohort of National Emphysema Treatment Trial. Briefly, severe and very severe chronic obstructive pulmonary disease (COPD) patients who were candidate for volume reduction surgery and who could provide sufficient data at 12-month follow-up were included. We used two anchor methods using 6-minute walk distance (6MWD. MCID = 40 m) and forced expiratory volume in 1 sec (FEV1. MCID = 100 ml) as anchors, and two distribution methods. We proposed MCID with a median of estimated values. We estimated MCID for DLCO in raw value and % change from the baseline independently. Results: The surgical cohort included 356 patients, whose average age was 66.6 ± 5.5 years, and the average % predicted FEV1 was 27.8 ± 7.3%. The estimated MCID for DLCO in raw value and % change from the baseline were as follows: anchor method (average, 6MWD) 1.2 ml/min/mmHg, 17%
anchor method (average, FEV1) 0.7 ml/min/mmHg, 11%
anchor method (receiver operating characteristic, 6MWD) 1.1 ml/min/mmHg, 10%
anchor method (receiver operating characteristic, FEV1) 1.2 ml/min/mmHg, 3%
distribution method (0.3 units of standard deviation), 0.9 ml/min/mmHg, 11%
distribution method (standard error of measurement), 1.1 ml/min/mmHg. The median of these values was 1.1 ml/min/mmHg and 11%. Conclusion: We estimated the group-level MCID for DLCO for patients with severe and very severe COPD patients as 1.1 ml/min/mmHg and 11% of baseline DLCO.

DOI： 10.3109/15412555.2014.898051

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Internal Medicine  

Objective The impact of corticosteroids on acute respiratory distress syndrome (ARDS) mortality remains controversial following the publication of numerous trials, observational studies and meta-analyses. An updated meta-analysis is warranted, as a few original studies on this topic have been published since the last meta-analysis. Methods We searched for eligible articles using four databases. In particular, we included full-length original articles providing sufficient data for evaluating the impact of corticosteroid treatment on adult ARDS mortality in the form of odds ratios. A fixed model with the confidence interval method was used. An assessment of publication bias and sensitivity analyses were also conducted. Results We included 11 of 185 articles. The pooled odds ratio for corticosteroids with respect to all-cause mortality involving 949 patients was 0.77 [95% confidence interval (CI): 0.58-1.03, p=0.079] with strong heterogeneity (I2=70%, p&lt
0.001). The results of the sensitivity analysis, Begg-Kendall test (τ=0.53, p=0.024) and funnel plot consistently suggested the existence of strong publication bias. After six potentially unpublished cohorts were filled using Duval’s trim and fill method, the pooled odds ratio shifted to 1.11 (95% CI 0.86-1.44, p=0.427). In addition, the sensitivity analyses suggested that corticosteroid treatment has a different impact on mortality depending on the comorbidities and trigger events. Conclusion We were unable to confirm, based on the data of published studies, the favorable impact of corticosteroid therapy on mortality in overall ARDS cases. Published articles exhibit strong publication bias, and previous meta-analyses may be affected by this publication bias. Further research focusing on pathophysiology- or trigger event-specific ARDS is anticipated.

DOI： 10.2169/internalmedicine.54.4015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AME Publishing Company  

The roll by the cytotoxic chemotherapy and its efficacy in the treatment of non-small cell carcinoma (NSCLC) was not clearly identified until the 1980s when studies showed that cisplatin was beneficial in the treatment of NSCLC. The first randomized controlled trial (RCT) to evaluate the efficacy of post-operative (adjuvant) chemotherapy using the cisplatin regimen for resectable NSCLC was reported in 1988. Since then, an increasing number of RCTs have been carried out to evaluate post-operative chemotherapy. Pre-operative (neo-adjuvant) chemotherapy is a relatively new treatment strategy, as its name indicates. Compared with post-operative chemotherapy, fewer RCTs have been carried out to evaluate preoperative chemotherapy. Given the inconsistency of the results from the RCTs, at least 12 meta-analyses have been published. Most of these meta-analyses reported overall survival (OS) benefit with hazard ratios (HRs) in the range of 0.81 to 0.89 in favor of pre-operative chemotherapy. An individual patient data metaanalysis by Burdett in 2014 indicates that the option of pre-operative chemotherapy + surgery is associated with better OS (HR 0.87, 95% CI, 0.78-0.96, P=0.007) and recurrence-free survival (RFS) (HR 0.85, 95% CI, 0.76-0.94, P=0.002) survival for operable NSCLC when compared with treatment with surgery alone. Although the current consensus recommends the use of post-operative chemotherapy, pre-operative chemotherapy has equivalent efficacy. Both strategies should be regarded as the first choice treatment options. Despite Burdett's comment, indication of pre-operative chemotherapy for stage IA disease should be judged carefully.

DOI： 10.3978/j.issn.2218-6751.2014.07.03

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BioMed Central Ltd.  

Background: Recent observational studies have suggested that use of statins reduces mortality in patients suffering from chronic obstructive pulmonary disease. However, no meta-analysis has reported the pooled hazard ratio of statins to all-cause mortality.Methods: We searched for eligible articles using five databases. We included randomized controlled trials and cohort studies written in English using original data reporting the hazard ratio of statins to all-cause, cardiovascular-related, cancer-related, or respiratory-related mortality. A fixed model with the confidence interval method was used. Publication bias was evaluated by funnel plot and Begg's test, and was corrected using Duval's trim and fill method. Sensitivity analyses were also conducted.Results: We included 10 out of 128 articles. The pooled hazard ratio of statins to all-cause mortality involving 16269 patients was 0.81 (95% CI: 0.75-0.86, P &lt
0.001) with moderate heterogeneity (I2 = 52%, P = 0.032). The sensitivity analysis and funnel plot suggested the existence of publication bias. After three possibly unpublished cohorts were imputed, the pooled hazard ratio of 0.83 (95% CI: 0.78-0.88, P &lt
0.001) still suggested a favorable prognosis in statin-treated patients. The pooled hazard ratio of statins to cardiovascular-related, cancer-related, and respiratory-related mortality were 0.52 (95% CI: 0.27-1.01, P = 0.052), 0.57 (95% CI: 0.32-1.01, P = 0.056), and 0.55 (95% CI: 0.43-0.78, P &lt
0.001), respectively, although these results were not conclusive as we could not find a sufficient number of original studies dealing with those forms of mortality.Conclusions: The use of statins for patients suffering from chronic obstructive pulmonary disease may reduce all-cause mortality. This conclusion should be re-evaluated by a registered large-scale randomized controlled trial. © 2014 Horita et al.
licensee BioMed Central Ltd.

DOI： 10.1186/1465-9921-15-80

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BioMed Central Ltd.  

Background:Oral corticosteroids were used to control stable chronic obstructive pulmonary disease (COPD) decades ago. However, recent guidelines do not recommend long-term oral corticosteroids (LTOC) use for stable COPD patients, partly because it causes side-effects such as respiratory muscle deterioration and immunosuppression. Nonetheless, the impact of LTOC on life prognosis for stable COPD patients has not been clarified.Methods:We used the data of patients randomized to non-surgery treatment in the National Emphysema Treatment Trial. Severe and very severe stable COPD patients who were eligible for volume reduction surgery were recruited at 17 clinical centers in the United States and randomized during 1998-2002. Patients were followed-up for at least five years. Hazard ratios for death by LTOC were estimated by three models using Cox proportional hazard analysis and propensity score matching.Results:The pre-matching cohort comprised 444 patients (prescription of LTOC:23.0%. Age:66.6 ± 5.4 year old. Female:35.6%. Percent predicted forced expiratory volume in one second:27.0 ± 7.1%. Mortality during follow-up:67.1%). Hazard ratio using a multiple-variable Cox model in the pre-matching cohort was 1.54 (P = 0.001). Propensity score matching was conducted with 26 parameters (C-statics:0.73). The propensity-matched cohort comprised of 65 LTOC(+) cases and 195 LTOC(-) cases (prescription of LTOC:25.0%. Age:66.5 ± 5.3 year old. Female:35.4%. Percent predicted forced expiratory volume in one second:26.1 ± 6.8%. Mortality during follow-up:71.3%). No parameters differed between cohorts. The hazard ratio using a single-variable Cox model in the propensity-score-matched cohort was 1.50 (P = 0.013). The hazard ratio using a multiple-variable Cox model in the propensity-score-matched cohort was 1.73 (P = 0.001).Conclusions:LTOC may increase the mortality of stable severe and very severe COPD patients. © 2014 Horita et al.
licensee BioMed Central Ltd.

DOI： 10.1186/1465-9921-15-37

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Oral corticosteroids were used to control stable chronic obstructive pulmonary disease (COPD) decades ago. However, recent guidelines do not recommend long-term oral corticosteroids (LTOC) use for stable COPD patients, partly because it causes side-effects such as respiratory muscle deterioration and immunosuppression. Nonetheless, the impact of LTOC on life prognosis for stable COPD patients has not been clarified.
Methods: We used the data of patients randomized to non-surgery treatment in the National Emphysema Treatment Trial. Severe and very severe stable COPD patients who were eligible for volume reduction surgery were recruited at 17 clinical centers in the United States and randomized during 1998-2002. Patients were followed-up for at least five years. Hazard ratios for death by LTOC were estimated by three models using Cox proportional hazard analysis and propensity score matching.
Results: The pre-matching cohort comprised 444 patients (prescription of LTOC: 23.0%. Age: 66.6 +/- 5.4 year old. Female: 35.6%. Percent predicted forced expiratory volume in one second: 27.0 +/- 7.1%. Mortality during follow-up: 67.1%). Hazard ratio using a multiple-variable Cox model in the pre-matching cohort was 1.54 (P = 0.001). Propensity score matching was conducted with 26 parameters (C-statics: 0.73). The propensity-matched cohort comprised of 65 LTOC(+) cases and 195 LTOC(-) cases (prescription of LTOC: 25.0%. Age: 66.5 +/- 5.3 year old. Female: 35.4%. Percent predicted forced expiratory volume in one second: 26.1 +/- 6.8%. Mortality during follow-up: 71.3%). No parameters differed between cohorts. The hazard ratio using a single-variable Cox model in the propensity-score-matched cohort was 1.50 (P = 0.013). The hazard ratio using a multiple-variable Cox model in the propensity-score-matched cohort was 1.73 (P = 0.001).
Conclusions: LTOC may increase the mortality of stable severe and very severe COPD patients.

DOI： 10.1186/1465-9921-15-37

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objective
The Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) is a quality-of-life (QOL) questionnaire that proved to correlate with St. George's Respiratory Questionnaire. Correlations between CAT scores and other COPD parameters have not been thoroughly evaluated in Japanese outpatients.
Methods
Cross-sectional study of 85 outpatients with COPD at a Japanese community-based hospital.
Patients
We observed 70 men and 15 women, whose average age was 72.0 +/- 9.0 years. Mean forced expiratory volume in 1 s (FEV1) (% predicted) was 45.8 +/- 14.7%. Mean CAT score was 10.1 +/- 7.9 (range: 0-31). We calculated Spearman's rank correlation coefficient for CAT score and the following variables: r = 0.81 for 'the Body Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index'; r = -0.05 for body mass index; r = -0.56 for FEV1 (% predicted); r = 0.88 for Modified Medical Research Council Dyspnea Scale; r = -0.71 for 6-min walk distance; r = 0.68 for 'the Age, Dyspnoea,and Airflow Obstruction Index'; and r = -0.40 for oxygen saturation in artery. Each COPD parameter, except for body mass index, had a significant (P &lt; 0.001) correlation with the CAT score.
Conclusions
The CAT score, which is obtainable by a simple questionnaire originally designed for QOL assessment, had strong correlations with airflow obstruction, dyspnea, exercise tolerance, prognostic index and oxygenation in Japanese outpatients.

DOI： 10.1111/crj.12062

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

Minimum clinically important change of 5 points in the University of California, San Diego Shortness of Breath Questionnaire (SOBQ) is established, but cutoff values between a small, a moderate, and a large change are still unknown. We used the data set of National Emphysema Treatment Trial consisting of severe and very severe chronic obstructive pulmonary disease patients, whose mean age was 64 years. Changes from baseline to post-surgical 6-month follow-up were evaluated. The St. George's Respiratory Questionnaire was used as anchor: vertical bar Delta SGRQ vertical bar &lt; 4, meaningless change; 4 &lt;= vertical bar Delta SGRQ vertical bar &lt; 8, small change; 8 &lt;= vertical bar Delta SGRQ vertical bar &lt; 13, moderate change; 13 &lt;= vertical bar Delta SGRQ vertical bar, large change. We decided the final cutoff values for the SOBQ as medians of the three anchor methods. We also decided the range of cutoff values as the range of three values. In a cohort of surgically treated patients (N = 484), we propose value of 5 (range 5-6), 11 (range 9-15), and 16 (range 14-20) for the cutoff values between a meaningless and a small change (minimum clinically important difference), a small and a moderate change, and a moderate and a large change, respectively. In a cohort of medically treated patients, numbers of patients categorized according to Delta SGRQ scores were similar to those of the patients categorizes according to the Delta SGRQ (N = 480) or Delta Forced expiratory volume in 1 second (N = 425). We propose group-level cutoff values and range between a small, a moderate, and a large changes.

DOI： 10.3109/15412555.2013.808615

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier  

Oral mesalazine, or 5-aminosalicylate, is one of the first-choice medications for the treatment of ulcerative colitis and is commonly used for both induction and maintenance therapy. In a 6-month period, we treated three cases of mesalazine-induced pneumonitis. In all three cases, computed tomography images revealed upper lobe dominant bilateral peripherally localized consolidations. Such images are commonly observed in patients with cryptogenic organizing pneumonia or chronic eosinophilic pneumonia. Computed tomography images for mesalazine-induced pneumonitis have been rarely reported in the literature. © 2014 The Japanese Respiratory Society.

DOI： 10.1016/j.resinv.2013.12.002

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記述言語：英語  

Studies on the sensitivity and specificity of the Binax Now Streptococcus pneumonia urinary antigen test (index test) show considerable variance of results. Those written in English provided sufficient original data to evaluate the sensitivity and specificity of the index test using unconcentrated urine to identify S. pneumoniae infection in adults with pneumonia. Reference tests were conducted with at least one culture and/or smear. We estimated sensitivity and two specificities. One was the specificity evaluated using only patients with pneumonia of identified other aetiologies ('specificity (other)'). The other was the specificity evaluated based on both patients with pneumonia of unknown aetiology and those with pneumonia of other aetiologies ('specificity (unknown and other)') using a fixed model for meta-analysis. We found 10 articles involving 2315 patients. The analysis of 10 studies involving 399 patients yielded a pooled sensitivity of 0.75 (95% confidence interval: 0.71-0.79) without heterogeneity or publication bias. The analysis of six studies involving 258 patients yielded a pooled specificity (other) of 0.95 (95% confidence interval: 0.92-0.98) without no heterogeneity or publication bias. We attempted to conduct a meta-analysis with the 10 studies involving 1916 patients to estimate specificity (unknown and other), but it remained unclear due to moderate heterogeneity and possible publication bias. In our meta-analysis, sensitivity of the index test was moderate and specificity (other) was high
however, the specificity (unknown and other) remained unclear. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

DOI： 10.1111/resp.12163

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The benefit of preoperative chemotherapy for resectable non-small-cell lung cancer is still controversial. Patients and Methods: We conducted fixed-model metaanalysis including randomized controlled trials comparing 'preoperative chemotherapy plus surgery' and 'surgery alone' as a primary study with sufficient data to provide a hazard ratio for overall survival. MEDLINE and Cochrane databases were used for the study search. Results: We found 16 studies. Seven included only stage III disease cases, and 9 were conducted without stage limitation. Sixteen trials involving 3728 samples observing 2326 deaths yielded a pooled hazard ratio for overall survival of 0.84 (95% confidence interval [CI], 0.77-0.91
P &lt
.001) with moderate heterogeneity (I2 = 40%). In sensitivity analysis, strong heterogeneity (I2 = 69%) was found between the 7 trials covering only stage III disease and 9 trials without stage limitation. The 7 studies evaluating only stage III disease involving 1447 samples and 1068 deaths yielded a pooled hazard ratio of 0.77 (95% CI, 0.68-0.87
P &lt
.001) with nonsignificant low heterogeneity (I2 = 17%). No publication bias was observed throughout this study. The effect of preoperative chemotherapy differs among stages. The pooled hazard ratio comparing 'preoperative chemotherapy plus surgery' and 'surgery alone' for patients with stage III disease in our study was 0.77, which is slightly better than the pooled hazard ratio of 0.83 in the Lung Adjuvant Cisplatin Evaluation study that compared 'surgery plus postoperative chemotherapy' and 'surgery alone.' Conclusion: Preoperative chemotherapy plus surgery for stage III disease is more effective than previously considered. © 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cllc.2013.03.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Some investigations have revealed an association between depression and physical measurements of COPD patients in North America and Europe, but few related studies have been performed in Asia. METHODS: In this cross-sectional study, 84 consecutive, stable outpatients with COPD (mean ±SD age 72.±0 9.0 y, percent-of-predicted FEV1 46 15%, 15 [17.9%] female) in a Japanese community hospital were recruited. "Probable depression" was defined as a score of &gt
6 on the short-form Geriatric Depression Scale (SF-GDS). Relationships among commonly used physical measurements, SF-GDS raw score, and probable depression were evaluated with the Spearman rank correlation test, multiple linear regression analysis, logistic regression analysis, and receiver operating characteristic curves. RESULTS: Thirty-two subjects (38.1%) had probable depression. Body mass index, obstruction, dyspnea, exercise capacity index, percent-of-predicted FEV1 Modified Medical Research Council dyspnea score, 6-min walk distance, and SpO2 had: simple correlations (r 0.42 - 0.60, P &lt
.001 for all) with the SF-GDS raw score
partial correlations (r 0.25 - 0.51, P &lt
.05 for all) with the SF-GDS raw score after adjusting for demographic and social factors
association with probable depression in the logistic regression analysis after adjusting for demographic and social factors (P &lt
.05 for all)
and areas under the receiver operating characteristic curve of 0.72 - 0.84 (P &lt
.001 for any) for probable depression. CONCLUSIONS: Physical parameters were associated with depression in our Japanese COPD out-patients. © 2013 Daedalus Enterprises.

DOI： 10.4187/respcare.02065

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Estimation of performance status (PS) has been assessed as a tool to determine which patients with newly diagnosed pulmonary TB (PTB) are most at risk of dying. This simple prediction rule has not been validated in patients with PTB with different background characteristics and from different geographic areas. Methods: A retrospective cohort study was conducted in two Japanese hospitals in different regions and included 432 inpatients with newly diagnosed smear-positive non-multidrug-resistant lung TB without HIV infection. The patients had a mean ± SD age of 64.9 ± 19.7 years and 135 were female (31.3%). Detailed nursing charts were reviewed to estimate PS, which was graded 0 (best condition), 1, 2, 3 or 4 (worst condition), for each patient. Results: Single variable and multivariable Cox regression analyses models revealed that a one-point increase in PS was associated with a 2.8-fold (95% CI 2.2-3.6) and 2.3-fold (95% CI 1.8-3.0), adjusted for age, gender, comorbidities and treatment regimen, increase in the HR for death (p &lt
0.001 for both models). Kaplan-Meier curves also showed a significant difference in mortality among different PS groups (p &lt
0.001). Conclusion: PS was strongly associated with mortality from PTB in the study cohort. Estimation of PS at the start of treatment for newly diagnosed PTB patients could be a useful tool in case management in resource-limited countries. © Royal Society of Tropical Medicine and Hygiene 2013. All rights reserved.

DOI： 10.1093/trstmh/trt037

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Long-acting beta-agonists were one of the first-choice bronchodilator agents for stable chronic obstructive pulmonary disease. But the impact of long-acting beta-agonists on mortality was not well investigated.Methods: National Emphysema Treatment Trial provided the data. Severe and very severe stable chronic obstructive pulmonary disease patients who were eligible for volume reduction surgery were recruited at 17 clinical centers in United States during 1988-2002. We used the 6-10 year follow-up data of patients randomized to non-surgery treatment. Hazard ratios for death by long-acting beta-agonists were estimated by three models using Cox proportional hazard analysis and propensity score matching were measured.Results: The pre-matching cohort was comprised of 591 patients (50.6% were administered long-acting beta-agonists. Age: 66.6 ± 5.3 year old. Female: 35.4%. Forced expiratory volume in one second (%predicted): 26.7 ± 7.1%. Mortality during follow-up: 70.2%). Hazard ratio using a multivariate Cox model in the pre-matching cohort was 0.77 (P = 0.010). Propensity score matching was conducted (C-statics: 0.62. No parameter differed between cohorts). The propensity-matched cohort was comprised of 492 patients (50.0% were administered long-acting beta-agonists. Age: 66.8 ± 5.1 year old. Female: 34.8%. Forced expiratory volume in one second (%predicted) 26.5 ± 6.8%. Mortality during follow-up: 69.1%). Hazard ratio using a univariate Cox model in the propensity-matched cohort was 0.77 (P = 0.017). Hazard ratio using a multivariate Cox model in the propensity-matched cohort was 0.76 (P = 0.011).Conclusions: Long-acting beta-agonists reduce mortality of severe and very severe chronic obstructive pulmonary disease patients. © 2013 Horita et al.
licensee BioMed Central Ltd.

DOI： 10.1186/1465-9921-14-62

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and objective We evaluated the association between activities of daily living and drug-induced liver injury by anti-tuberculosis drugs. Methods This retrospective cohort study included adult inpatients with newly diagnosed smear-positive lung tuberculosis treated with standard regimen in two hospitals. (n = 346
63.6 ± 20.3 years old
106 (30.6%) females). Activities of daily living was divided into 'independent' (Barthel Index (BI) 80-100, 60.4%) and 'decreased' (BI 0-75, 39.6%) categories. Liver injury was defined as the withdrawal or change of treatment regimen on the basis of the following criteria: serum transaminase concentrations were more than three times the upper limit of normal range with jaundice and/or hepatitis symptoms, or more than five times the upper limit of the normal range. Results Compared with 'independent' patients, patients with 'decreased' activities of daily living had odds ratios for liver injury of 4.2 (P &lt
0.001) in univariate analysis and 5.7 (P = 0.002) in logistic regression analysis after adjusting for other risk factors. Conclusions Decreased activity of daily living is a strong risk factor for liver injury among adult inpatients with newly diagnosed smear-positive lung tuberculosis treated using a standard regimen. This retrospective cohort study included adult inpatients having newly diagnosed smear-positive lung tuberculosis treated with a standard regimen (N = 346). Patients with decreased activities of daily living had an odds ratio of 5.7 for drug-induced liver injury after adjusting for 11 other risk factors. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

DOI： 10.1111/resp.12008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: No scoring system has ever been used to estimate the prognosis of individual tuberculosis (TB) patients. OBJECTIVE: To develop and validate a tuberculosis prognostic score. METHODS: This retrospective cohort study conducted in Japan comprised the development (n = 179
mean age 65.9 ± 18.8 years) and validation (n = 244
mean age 64.3 ± 20.1 years) of a tuberculosis prognostic score among patients with newly diagnosed smear-positive non-multidrug-resistant pulmonary tuberculosis without human immunodeficiency virus infection. The score (raw score) was defined by modifying a logistic regression formula using known risk factors as independent variables and in-patient death as a dependent variable. RESULTS: The raw score was calculated as follows: age (years) + (oxygen requirement, 10 points) - 20 x albumin (g/dl) + (activity of daily living: independent, 0 point
semi-dependent, 5 points
totally dependent, 10 points). The raw scores were grouped into risk groups 1 (raw score &lt
-30) to 5 (raw score ≥ 60) using 30-point intervals. Every increase in risk group was equivalent to a 7.3-fold increase in the odds ratio for in-hospital death (P &lt
0.001). The area under the receiver operating characteristics curve by risk group for in-patient death was 0.875 (P &lt
0.001). CONCLUSIONS: In this study we were able to develop and validate a tuberculosis prognostic score. © 2013 The Union.

DOI： 10.5588/ijtld.12.0476

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective No studies have so far sufficiently investigated the risk factors for drug-induced liver injury (DILI) with an elevated serum bilirubin concentration.
Methods We conducted a historical cohort study observing inpatients admitted to two hospitals in Japan. A decreased level of activities of daily living (ADL) was defined as a Barthel Index score of &lt;80. The patients were treated with standard regimens under a directly observed treatment short-course strategy.
Results The cohort of 356 patients comprised 244 men (68.5%) and 112 women (31.5%), with a mean age of 63.8 +/- 20.2 years. Compared with the patients who did not experience DILI with a bilirubin level of &gt;= 2.0 mg/dL, the patients who experienced DILI with a bilirubin level of &gt;= 2.0 mg/dL more often had a decreased level of ADLs, were more likely to suffer from chronic cardiac disease, had lower serum albumin levels and were less often treated with four-drug regimens involving pyrazinamide (PZA). In a logistic regression analysis in which these five factors acted as independent variables, a decreased level of ADLs was the strongest predictor for DILI with a bilirubin level of &gt;= 2.0 mg/dL, with an odds ratio of 16.5 (95% CI: 1.7-159; p=0.015), followed by chronic cardiac disease, with an odds ratio of 4.0 (95% CI: 1.2-12.6; p=0.020).
Conclusion A decreased level of ADLs and chronic cardiac disease are strong risk factors for DILI with a bilirubin level of &gt;= 2.0 mg/dL resulting from the use of antituberculous drugs. Physicians should pay close attention to the possibility of DILI with a bilirubin level of &gt;= 2.0 mg/dL when treating tuberculosis patients with a decreased level of ADLs and/or chronic heart disease.

DOI： 10.2169/internalmedicine.52.0545

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Allergology  

Background: Single inhaled corticosteroids and long-acting beta-agonists (ICS/LABA) are clinically effective and safe. However, if local oropharyngeal and laryngeal adverse effects (LOLAE) appear, adherence to the use of ICS is impaired. To minimize the development of adverse effects, it is essential to identify the underlying risk factors. Methods: The study included 481 asthmatic patients who were prescribed ICS/LABA for the first time in their life between January and September of 2010. Patients ranged in age from 14 to 86 years old and consisted of 281 never smokers and 200 smokers. All data were collected retrospectively by respirologists. Results: Seventy-three out of 481 patients suffered from one or more adverse effects, with 54 of these exhibiting LOLAE. Patients with LOLAE (51.4 ± 16.2 yrs) were significantly older than those without LOLAE (43.7 ± 15.9 yrs) (p = 0.0011) and were also prescribed a significantly higher dose of ICS. The pack-years of patients with LOLAE (2.1 ± 4.9) were significantly lower than those without LOLAE (6.0 ± 13.0) (p = 0.0087). The type of administered ICS was also significantly associated with a risk of developing LOLAE. Conclusions: Our survey indicated that a greater age, a higher dose of ICS, and the type of ICS were potential risk factors of LOLAE. The identified factors should be considered in a clinical setting in order to prevent the development of LOLAE and provide optimal treatment to patients. © 2012 Japanese Society of Allergology.

DOI： 10.2332/allergolint.11-OA-0396

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective There are no rules to predict the time to infectivity negative conversion based on sputum smear conversion or culture conversion during chemotherapy in smear-positive tuberculosis patients. We aimed to develop and validate rules of sputum smear grades and cavitations in the lungs due to tuberculosis. Methods This study was a retrospective cohort study that consisted of development (n=158, 64±19 years of age) and validation (n=214, 63±20 years of age) steps in different cohorts. We developed a rule with pretreatment smear grades and the existence of cavitations in the lungs due to tuberculosis as independent variables and the duration to infectivity negative conversion as the dependent variable in a Cox hazard model. The smear grade indicating the pretreatment bacterial load was classified into four grades according to the Japanese guidelines. The presence of cavitations was assessed on X-ray. Infectivity conversion was defined according to the criteria of the Japanese Ministry of Health, Labour and Welfare: A patient is currently receiving proper treatment and shows clinical improvement and sputum smears and cultures in any combination are consecutively negative three times. Results Development We developed an “Infectivity Conversion Score” classifying each patient with a smear grade of I though IV and assessing the existence of cavitations in the lungs due to tuberculosis. Validation The median time to infectivity conversion in the validation cohort was 13, 22, 35 and 50 days for Infectivity Conversion Scores I through IV, respectively (p&lt
0.001). Conclusion We developed and validated Infectivity Conversion Scores. © 2012, The Japanese Society of Internal Medicine. All rights reserved.

DOI： 10.2169/internalmedicine.51.8585

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Approximately 10% of asthmatic patients are refractory to inhaled corticosteroids and there-fore need long-term oral corticosteroid therapy, which is associated with a risk of opportunistic infections due to immunosuppression. Objective To ascertain the applicability of serum Immunoglobulin G (IgG) as a marker for predicting the risk of opportunistic infections in patients undergoing oral corticosteroid therapy. Methods Three thousand asthmatics were screened, and 14 patients who had been administered daily oral corticosteroids for more than two years were enrolled. The patients enrolled were maintained under observa-tion with ordinary check-ups and treatments for one year. After the observation period, the patients were di-vided into two groups according to the presence (OPI) or absence (Non-OPI) of opportunistic infections dur-ing the period. The differences in the clinical parameters between the groups were investigated. Results There were no statistically significant differences in age, forced expiratory volume in 1 second (FEV1), smoking status or serum albumin between the groups. The serum IgG level of the OPI group was significantly lower than that of the Non-OPI group (567.2±151.1 mg/dL vs. 931.6±198.8 mg/dL, p&lt
0.01). The average total dose of corticosteroids administered during the one year period was higher in the OPI group (2,633±554.2 mg) than that in the Non-OPI group (1,793±466.2 mg) (p&lt
0.05). There was a significant correlation between the serum IgG and total dose of corticosteroids administered during the one-year period (r=-0.75, p&lt
0.01). The area under the receiver operating characteristic curve regarding the serum IgG and in-cidence of opportunistic infections was 0.97, which suggests that the serum IgG level has a high accuracy for predicting the risk of opportunistic infections. Conclusion The serum IgG was therefore found to be a useful marker for predicting the risk of opportunis-tic infections in steroid-dependent asthmatics. © 2012 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.51.7775

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) occurs during the chronic progressive course of idiopathic pulmonary fibrosis. Mortality is estimated to be &gt
70%, because no effective treatment has been established. We evaluated the effectiveness of combination therapy of tacrolimus and methylprednisolone for AE-IPF. Methods Patients of AE-IPF treated with methylprednisolone pulse therapy with or without tacrolimus (targeting 20 ng/mL) during the period between January 2001 and April 2010 were retrospectively reviewed. The primary endpoints were survival rate and duration. We also observed lactate dehydrogenase levels, partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio), KL-6, occurrence of re-exacerbation, and computed tomography score. Results Fifteen Japanese patients [tacrolimus group aged 74.2±6.0 years old (n=5), non-tacrolimus group aged 75.1±12.8 years old (n=10)] were identified. Pre-treatment clinical parameters were not significantly different between the two groups. Four of 5 tacrolimus group patients and 1 of 10 non-tacrolimus group patients survived (p&lt
0.05). The median survival durations were &gt
92 days (tacrolimus group) and 38 days (nontacrolimus group) (p&lt
0.05). Lactate dehydrogenase levels and the P/F ratio were also significantly favorable in the tacrolimus group. KL-6 and CT score were not significantly different in both groups. Four re-acute exacerbations were observed only in the non-tacrolimus group. Conclusion Combined tacrolimus and methylprednisolone pulse therapy mitigates AE-IPF, prevents re-acute exacerbation, and contributes to a better prognosis. © 2011 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.50.4327

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：英語   出版者・発行元：Elsevier B.V.  

DOI： 10.1016/j.resinv.2015.09.006

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：John Wiley and Sons Ltd  

This is the protocol for a review and there is no abstract. The objectives are as follows: To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of patients with stable COPD.

DOI： 10.1002/14651858.CD012066

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

Topotecan is the most reliable chemotherapy regimen for relapsed small-cell lung carcinoma (SCLC). The efficacy and adverse effects of topotecan as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for 6-month over-all survival (OS) rate, 1-year OS rate, objective responses, and/or adverse effects of single agent topotecan as a second line chemotherapy for SCLC, written in English language as a full article. Any topotecan regimen were allowed. Binary data were meta-analyzed with the random-model generic inverse variance method. We included 14 articles consisted of 1347 patients. Pooled values were estimated as follows. &lt;Refractory relapse&gt; Six-month OS rate: 37% (95% CI: 28-46%). One-year OS rate: 9% (95% CI: 5-13%). Response rate: 5% (95% CI: 1-8%). &lt;Sensitive relapse&gt; Six-month OS rate: 57% (95% CI: 50-64%). One-year OS rate: 27% (95% CI: 22-32%). Response rate: 17% (95% CI: 11-23%). &lt;Adverse effect&gt; Grade III/IV neutropenia 69% (95% CI: 58-80%). Grade III/IV thrombopenia 41% (95% CI: 34-48%). Grade III/IV anemia 24% (95% CI: 17-30%). Non-hematorogical events were rare. Chemotherapy-related death 2% (95% CI: 1-3%). In conclusion, Topotecan provided a possibly promising outcome for sensitive-relapse SCLC and poor outcome for refractory relapse SCLC. Adverse events were mainly hematological.

DOI： 10.1038/srep15437

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記述言語：英語   出版者・発行元：Elsevier B.V.  

A case-control study often compares the prevalence of a specific disease among persons with normal alleles and persons with variant alleles, which generates an odds ratio (OR). The most common type of allele variation, single-nucleotide polymorphism, consists of a major allele (M) and a minor allele (m). Thus, the genotype can be a major allele homozygote (MM), a heterozygote (Mm) or a minor allele homozygote (mm). Odds are given for each genotype, and a pair of odds generates an OR. Summarizing data using two-by-two contingency is the simplest method of estimating an OR. Thus, dominant, multiplicative, recessive, and over-dominant models are often used. Traditionally, researchers used to calculate ORs using many models and then select the best model from among these calculated ORs. This may cause problems due to multiple comparisons. Therefore, we should choose the best model before calculating the OR for each model. In this article, we will discuss how to choose the best model among many subject-level models when evaluating the impact of the MM/Mm/mm genotype on the disease prevalence.

DOI： 10.1016/j.mgene.2015.04.003

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：NATURE PUBLISHING GROUP  

Previous randomized controlled trials (RCTs) and meta-analyses evaluated the efficacy and safety of adjunctive corticosteroids for community-acquired pneumonia (CAP). However, the results from them had large discrepancies. The eligibility criteria for the current meta-analysis were original RCTs written in English as a full article that evaluated adjunctive systemic corticosteroids adding on antibiotic therapy targeting typical and/or atypical pathogen for treating hospitalized human CAP cases. Four investigators independently searched for eligible articles through PubMed, Embase, and Cochrane databases. Random model was used. The heterogeneity among original studies and subgroups was evaluated with the I-2 statistics. Of 54 articles that met the preliminary criteria, we found 10 eligible RCTs comprising 1780 cases. Our analyses revealed following pooled values by corticosteroids. OR for all-cause death: 0.80 (95% confidence interval (95% CI) 0.53-1.21) from all studies; 0.41 (95% CI 0.19-0.90) from severe-case subgroup; 0.21 (95% CI 0.0-0.74) from intensive care unit (ICU) subgroup. Length of ICU stay: -1.30 days (95% CI (-3.04)-0.44). Length of hospital stay: -0.98 days (95% CI (-1.26)-(-0.71)). Length to clinical stability: -1.16 days (95% CI (-1.73)(- 0.58)). Serious complications do not seem to largely increase by steroids. In conclusion, adjunctive systemic corticosteroids for hospitalized patients with CAP seems preferred strategies.

DOI： 10.1038/srep14061

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：Elsevier B.V.  

DOI： 10.1016/j.resinv.2015.01.006

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：Dove Medical Press Ltd.  

Once-daily dual-bronchodilator therapy with combined indacaterol and glycopyrronium bromide in one device (Ultibro, Breezhaler), often called QVA149, was first approved in 2013 in Japan and Europe. As of November 2014, more than 40 countries had approved this medication except for the USA. This is the first dual bronchodilator in one device. Now, the Breezhaler is the only device that can provide long-acting muscarinic antagonist (glycopyrronium bromide), long-acting beta agonist (indacaterol), and a combination of the two medications (QVA149). The choice among the three medications allows a patient to use the same inhalation device even when the regimen is changed from single-bronchodilator therapy to dual-bronchodilator therapy. In addition, the quick bronchodilation effect and once-daily administration can improve patient adherence to medical treatment for chronic obstructive pulmonary disease (COPD). To our knowledge, as of November 2014, the safety and the efficacy of QVA149 have been evaluated in 14 randomized controlled trials. The 14 trials generally showed good safety profiles, and there were better or not-inferior bronchodilator effects of QVA149 when compared with placebo, or other inhaled medication. According to the Japanese Respiratory Society guidelines, QVA149 is a combination of the two first-line bronchodilators. Our meta-analysis indicated that QVA149 is superior to the salmeterol–fluticasone combination to treat COPD in respect of the frequency of adverse effects, exacerbation, pneumonia, and improvement of trough forced expiratory volume in 1 second (FEV&lt
inf&gt
1&lt
/inf&gt
). Thus, we believe that QVA149 can be a key medication for COPD treatments.

DOI： 10.2147/COPD.S56067

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：WILEY-BLACKWELL  

Background and objective: Genetic susceptibility for development of chronic obstructive pulmonary disease (COPD) is under intensive investigation. Among the three alleles of vitamin D binding protein, or group-specific (GC) components, some have suggested that having GC-1F and GC-2 alleles was associated with a risk of COPD. Although previous studies have shown considerable variance, no meta-analysis has been conducted.
Methods: Through four databases, two independent investigators searched for case-control studies providing sufficient data to calculate odds ratios by the vitamin D binding protein allele variant and genotype variant for a case of COPD. Studies whose control did not satisfy the Hardy-Weinberg equilibrium (Chi-square P0.05) were excluded. We used a fixed-model to estimate the pooled odds ratio at both allele and genotype level.
Results: Of 141 candidate studies, six were included. We analysed 1712 subjects, consisting of 466 Asians, 1246 Caucasians, 531 COPD cases and 1181 non-COPD controls. The prevalence of each allele among the 1181 controls was as follows: GC-1F 14.0%, GC-1S 53.8% and GC-2 31.9%. When compared to GC-1S, the GC-1F allele and GC-2 allele were associated with COPD risk with pooled odds ratios of 1.44 (95% CI 1.14-1.83, P=0.002) and 0.83 (95% CI 0.69-0.996, P=0.045), respectively. When compared to the 1S-1S genotype, the 1F-1F genotype was a risk factor of COPD with pooled odds ratio of 2.64 (95% CI 1.29-5.39, P=0.008).
Conclusion: The GC-1F allele of the vitaminD binding protein was a risk for COPD in recessive mode.

DOI： 10.1111/resp.12448

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：DOVE MEDICAL PRESS LTD  

Once-daily dual-bronchodilator therapy with combined indacaterol and glycopyrronium bromide in one device (Ultibro, Breezhaler), often called QVA149, was first approved in 2013 in Japan and Europe. As of November 2014, more than 40 countries had approved this medication except for the USA. This is the first dual bronchodilator in one device. Now, the Breezhaler is the only device that can provide long-acting muscarinic antagonist (glycopyrronium bromide), long-acting beta agonist (indacaterol), and a combination of the two medications (QVA149). The choice among the three medications allows a patient to use the same inhalation device even when the regimen is changed from single-bronchodilator therapy to dual-bronchodilator therapy. In addition, the quick bronchodilation effect and once-daily administration can improve patient adherence to medical treatment for chronic obstructive pulmonary disease (COPD). To our knowledge, as of November 2014, the safety and the efficacy of QVA149 have been evaluated in 14 randomized controlled trials. The 14 trials generally showed good safety profiles, and there were better or not-inferior bronchodilator effects of QVA149 when compared with placebo, or other inhaled medication. According to the Japanese Respiratory Society guidelines, QVA149 is a combination of the two first-line bronchodilators. Our meta-analysis indicated that QVA149 is superior to the salmeterol-fluticasone combination to treat COPD in respect of the frequency of adverse effects, exacerbation, pneumonia, and improvement of trough forced expiratory volume in 1 second (FEV1). Thus, we believe that QVA149 can be a key medication for COPD treatments.

DOI： 10.2147/COPD.S56067

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記述言語：日本語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：Japanese Society for Tuberculosis  

[Background]: In the 1950s, high doses (40-70 mg/kg/day) of pyrazinamide were reported to cause druginduced liver injury (DILI). It remains unclear whether adding pyrazinamide (Z) at the currently accepted low dose (20-25 mg/kg/day) to a regimen of isoniazid (H), rifampicin (R), and ethambutol (E) increases the risk of DILI. [Method]: We reviewed adult patients admitted for smearpositive tuberculosis who were treated with a daily HRE or HRZE regimen. A Cox model was used to analyze the impact of pyrazinamide on the occurrence of DILI. [Results]: We reviewed 195 patients (123 men [63%], 72 women [37%], average age 65 ± 19 years, 65 HRE patients [33%], 130 HRZE patients [67%]). The incidence of DILI in the first two months was 15% (29/195). The HRZE regimen was not associated with DILI (hazard ratio 0.55, P = 0.263). [Conclusion]: Addition of low-dose (20-25 mg/kg/day) pyrazinamide to the HRE regimen does not appeared to be associated with increased DILI incidence during the first two months of treatment.

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

DOI： 10.4187/respcare.02890

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