EBUS-centred versus EUS-centred mediastinal staging in lung cancer: a randomised controlled trial

Kang, Hyo Jae,Hwangbo, Bin,Lee, Geon-Kook,Nam, Byung-Ho,Lee, Hyun-Sung,Kim, Moon Soo,Lee, Jong Mog,Zo, Jae Ill,Lee, Hee Seok,Han, Ji-Youn BMJ Publishing Group Ltd 2014 Thorax Vol.69 No.3

<P><B>Background</B></P><P>The impact of procedure sequence and primary procedure has not been studied in the combined application of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in lung cancer staging.</P><P><B>Methods</B></P><P>In a randomised controlled trial, 160 patients with histologically confirmed or strongly suspected potentially operable non-small cell lung cancer were enrolled (Group A, n=80, EBUS-centred; Group B, n=80, EUS-centred). EBUS-TBNA and EUS-FNA with an ultrasound bronchoscope were used as the first procedures in Groups A and B, respectively, and secondary procedures (EUS-FNA in Group A, EBUS-TBNA in Group B) were added.</P><P><B>Results</B></P><P>Diagnostic values were evaluated in 148 patients (74 in each group). In Groups A and B the diagnostic accuracy (93.2% (95% CI 87.5% to 99.0%) vs 97.3% (95% CI 93.6% to 101.0%), p=0.245) and sensitivity (85.3% (95% CI 68.9% to 95.0%) vs 92.0% (95% CI 74.0% to 99.0%), p=0.431) in detecting mediastinal metastasis were not statistically different. In Group A, adding EUS-FNA to EBUS-TBNA did not significantly increase the accuracy (from 91.9% to 93.2%, p=0.754) or sensitivity (from 82.4% to 85.3%, p=0.742). In group B, adding EBUS-TBNA to EUS-FNA increased the accuracy (from 86.5% to 97.3%, p=0.016) and sensitivity (from 60.0% to 92.0%, p=0.008). There were no intergroup differences in procedure time, cardiorespiratory parameters during procedures, complications or patient satisfaction.</P><P><B>Conclusions</B></P><P>Using a combination of EBUS-TBNA and EUS-FNA in mediastinal staging, we found that diagnostic values and patient satisfaction were not different between the EBUS-centred and EUS-centred groups. However, the necessity for EBUS-TBNA following EUS suggests that EBUS-TBNA is a better primary procedure in endoscopic mediastinal staging of potentially operable lung cancer.</P><P><B>Trial Registration number</B></P><P>ClinicalTrials.gov number NCT01385111.</P>

Phase III, multicentre, double-blind, randomised, parallel-group study to evaluate the similarities between LBEC0101 and etanercept reference product in terms of efficacy and safety in patients with active rheumatoid arthritis inadequately responding to

Matsuno, Hiroaki,Tomomitsu, Masato,Hagino, Atsushi,Shin, Seonghye,Lee, Jiyoon,Song, Yeong Wook BMJ Publishing Group 2018 Annals of the Rheumatic Diseases Vol.77 No.4

<P><B>Objective</B></P><P>To evaluate the similarities between LBEC0101 (etanercept biosimilar) and the etanercept reference product (ETN-RP) in terms of efficacy and safety, including immunogenicity, in patients with active rheumatoid arthritis despite methotrexate treatment.</P><P><B>Methods</B></P><P>This phase III, multicentre, randomised, double-blind, parallel-group, 54-week study was conducted in Japan and Korea. The primary efficacy endpoint was the change from baseline in the disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at week 24. American College of Rheumatology 20% (ACR20) response rate, adverse events (AEs), pharmacokinetics and development of antidrug antibodies (ADAs) were also evaluated.</P><P><B>Results</B></P><P>In total, 374 patients were randomised to LBEC0101 (n=187) or ETN-RP (n=187). The least squares mean changes from baseline in DAS28-ESR at week 24 in the per-protocol set were −3.01 (95% CI −3.198 to −2.820) in the LBEC0101 group and −2.86 (95% CI −3.051 to −2.667) in the ETN-RP group. The estimated between-group difference was −0.15 and its 95% CI was −0.377 to 0.078, which was within the prespecified equivalence margin of −0.6 to 0.6. ACR20 response rates at week 24 were similar between the groups (LBEC0101 93.3% vs ETN-RP 86.7%). The incidence of AEs up to week 54 was comparable between the groups (LBEC0101 92.0% vs ETN-RP 92.5%), although fewer patients in the LBEC0101 group (1.6%) than the ETN-RP group (9.6%) developed ADAs.</P><P><B>Conclusion</B></P><P>The clinical efficacy of LBEC0101 was equivalent to that of ETN-RP. LBEC0101 was well tolerated and had a comparable safety profile to ETN-RP.</P><P><B>Trial registration number</B></P><P>NCT02357069.</P>

Expression of stanniocalcin-1 in culprit coronary plaques of patients with acute myocardial infarction or stable angina

Lee, Cheol Whan,Hwang, Ilseon,Park, Chan-Sik,Lee, Hyangsin,Park, Duk-Woo,Kang, Soo-Jin,Lee, Seung-Whan,Kim, Young-Hak,Park, Seong-Wook,Park, Seung-Jung BMJ Publishing Group Ltd 2013 Journal of clinical pathology Vol.66 No.9

<P><B>Background</B></P><P>Stanniocalcin-1 (STC1) is involved in fundamental biological processes such as angiogenesis, inflammation and wound healing, but little is known about its expression in human coronary atherosclerotic plaques or its relationship to plaque instability.</P><P><B>Objective</B></P><P>STC1 expression was examined in the culprit coronary plaques of 70 patients with acute myocardial infarction (AMI; n=49) or stable angina (n=21) who underwent directional coronary atherectomy.</P><P><B>Methods</B></P><P>The specimens were stained with H&E, STC1-specific antibodies, and endothelial cells, macrophages and smooth muscle cell markers.</P><P><B>Results</B></P><P>The baseline characteristics of the two groups of patients were largely similar. CD31-immunopositive and CD68-immunopositive areas, indicative of the presence of endothelial cells and macrophages, respectively, were proportionately larger while areas immunopositive for α-actin, as a smooth muscle cell marker, were proportionately smaller in the AMI group than in the stable angina group. The proportion of STC1-immunopositive areas was significantly greater in the AMI group than in the stable angina group (20.0% (8.2–29.0%) vs 8.8% (3.9–19.4%), p=0.022). Areas positive for STC1 were independently correlated with those immunopositive for CD31 (r=0.42, p<0.001) and CD68 (r=0.40, p<0.001). STC1 immunoreactivity co-localised with CD31-immunopositive and CD68-immunopositive cells.</P><P><B>Conclusions</B></P><P>STC1 is differentially expressed in the culprit coronary plaques of patients with AMI versus those with stable angina. STC1 may play a role in plaque instability.</P>

0199 Using machine learning to efficiently use multiple experts to assign occupational lead exposure estimates in a case-control study

Friesen, Melissa C,Locke, Sarah J,Zaebst, Dennis,Viet, Susan,Shortreed, Susan,Chen, Yu-Cheng,Koh, Dong-Hee,Pardo, Larissa,Schwartz, Kendra L,Davis, Faith G,Stewart, Patricia A,Colt, Joanne S,Purdue, M BMJ Publishing Group Ltd 2014 Occupational and environmental medicine Vol.71 No.suppl1

<P><B>Objectives</B></P><P>We applied machine learning approaches to efficiently assist multiple experts to transparently estimate occupational lead exposure in a case-control study of renal cell carcinoma.</P><P><B>Method</B></P><P>We used hierarchical cluster models to classify the 7154 study jobs with occupational history and job/industry questionnaires into 360 groups with similar responses. Each group was reviewed independently by two or three experts and was assigned probabilities of lead exposure (<5%, ≥5– <50%, ≥50%) for three time periods (<1980, 1980–1994, ≥1995). When the group’s mean response pattern suggested within-group exposure variability, experts identified programmable conditions that defined the rating differences where possible or flagged the group for further review. After splitting jobs that overlapped time periods at the calendar cut point, the 9992 job/time periods were assigned their relevant expert/group/time period estimate. Classification and regression tree (CART) models were developed to predict each expert’s expected assignment, based on previous decisions, to assign estimates for jobs in groups that expert had not assessed and for jobs requiring further review.</P><P><B>Results</B></P><P>In preliminary analyses, CART models predicted 91–96% of the experts’ pre-1995 estimates and 77–96% of ≥1995 estimates. CART estimates were assigned to 3–48% of the job/time periods, varying by expert. Overall, 92% of the job/time periods were assigned the same estimate by at least two experts.</P><P><B>Conclusions</B></P><P>Our framework reduced the number of exposure decisions needed from each expert compared to job-by-job assessment. Future work will use CART models to identify differences between experts to be resolved and incorporate frequency and intensity of lead exposure estimates.</P>

Gonadotropin ratio affects the <i>in vitro</i> growth of rhesus ovarian preantral follicles

Kim, Yoon Young,Yun, Jun-Won,Kim, Jong Min,Park, Chung Gyu,Rosenwaks, Zev,Liu, Hung Ching,Kang, Byeong-Cheol,Ku, Seung-Yup BMJ Publishing Group 2016 Journal of investigative medicine Vol.64 No.4

<P><I>In vitro</I> follicle growth (IVFG) strategy is critical in the fertility preservation of cancer survivors; however, its optimal protocol needs to be developed using primate models since the availability of human samples is limited. Only a few previous studies have reported the successful IVFG of rhesus monkey ovaries using low-dose follicle-stimulating hormone (FSH) (0.3 or 3 ng/mL) and long-term culture (up to 5 weeks) and it is still uncertain in regard to the optimal culture duration and effective dose of treated gonadotropins applicable to the IVFG of rhesus preantral follicles. Recently, we have reported that the FSH to luteinizing hormone (LH) ratio affects the <I>in vitro</I> growth of murine ovarian follicles. We aimed to investigate whether gonadotropin ratios affect the efficiency of rhesus follicular growth <I>in vitro</I>. Ovaries were collected from six necropsied rhesus macaques (4–9 years) and preantral follicles were retrieved and cultured for 14 days using 200 mIU/mL FSH. The characteristics of follicular growth were compared between the FSH:LH=1:1 (n=24) and FSH:LH=2:1 (n=24) groups. High concentration gonadotropin treatment shortened the duration required for <I>in vitro</I> maturation of rhesus preantral follicles. The FSH:LH=2:1 group showed a faster follicular growth and enabled the acquisition of mature oocytes, although the expression of growth differentiation factor (GDF)-9 and anti-Müllerian hormone (AMH) did not differ significantly between the two groups. Taken together, high dose gonadotropin treatment can shorten the duration of IVFG and the gonadotropin ratio is important in the IVFG of rhesus monkey ovaries.</P>

Randomised clinical trial of five ear acupuncture points for the treatment of overweight people

Yeo, Sujung,Kim, Kang Sik,Lim, Sabina BMJ Publishing Group Ltd 2014 ACUPUNCTURE IN MEDICINE Vol.32 No.2

<P><B>Objective</B></P><P>To evaluate the efficacy of the five ear acupuncture points (Shen-men, Spleen, Stomach, Hunger, Endocrine), generally used in Korean clinics for treating obesity, and compare them with the Hunger acupuncture point.</P><P><B>Methods</B></P><P>A randomised controlled clinical trial was conducted in 91 Koreans (16 male and 75 female, body mass index (BMI)≥23), who had not received any other weight control treatment within the past 6 months. Subjects were divided randomly into treatment I, treatment II or sham control groups and received unilateral auricular acupuncture with indwelling needles replaced weekly for 8 weeks. Treatment I group received acupuncture at the five ear acupuncture points, treatment II group at the Hunger acupuncture point only and the sham control group received acupuncture at the five ear acupuncture points used in treatment I, but the needles were removed immediately after insertion. BMI, waist circumference, weight, body fat mass (BFM), percentage body fat and blood pressure were measured at baseline and at 4 and 8 weeks after treatment.</P><P><B>Results</B></P><P>For the 58 participants who provided data at 8 weeks, significant differences in BMI, weight and BFM were found between the treatment and control groups. Treatment groups I and II showed 6.1% and 5.7% reduction in BMI, respectively (p<0.004). There were no significant differences between the two treatment groups.</P><P><B>Conclusions</B></P><P>This finding suggests that the five ear acupuncture points, generally used in Korean clinics, and the Hunger point alone treatment are both effective for treating overweight people.</P>

Progressive change in peripapillary atrophy in myopic glaucomatous eyes

Song, Min Kyung,Sung, Kyung Rim,Shin, Joong Won,Kwon, Junki,Lee, Ji Yun,Park, Ji Min BMJ Publishing Group Ltd 2018 British journal of ophthalmology Vol.102 No.11

<P><B>Aim</B></P><P>To evaluate the progressive change in peripapillary atrophy (PPA) according to its shape and to explore the relationship between PPA progression and glaucoma worsening in myopic eyes.</P><P><B>Methods</B></P><P>A total of 159 eyes of 159 patients with myopic (axial length (AXL) >24 mm) glaucoma (mean follow-up 4.4 years, 35 eyes with minimal PPA, 40 concentric-type PPA eyes (>270° around the optic disc) and 84 eccentric-type PPA eyes (<270°)) were included. Sequential stereoscopic colour optic disc photographs were evaluated to qualitatively determine PPA progression. Factors associated with PPA progression were explored by Cox proportional hazard modelling in each PPA group.</P><P><B>Results</B></P><P>Patients with concentric PPA were older than patients with eccentric PPA (54.1±11.7 vs 44.1±11.7 years; P<0.001), and AXL was longer in the eccentric group than in the other groups (25.54±1.68 vs 25.28±1.53 vs 26.41±1.29 mm; P<0.001). Twenty-six eyes (65%) in the concentric group and 36 eyes (42.9%) in the eccentric group showed PPA progression. Older age (hazard ratio (HR) 1.059, P=0.008), worse baseline visual field mean deviation (HR 0.857, P=0.009) and greater baseline PPA area (HR 1.000, P=0.012) were associated with PPA progression in the concentric type. Glaucoma progression (HR 3.690, P=0.002) and longer AXL (HR 1.521, P=0.002) were associated with PPA progression in the eccentric type.</P><P><B>Conclusions</B></P><P>Relationship between glaucoma worsening and PPA progression was strongest in myopic glaucomatous eyes with eccentric type PPA.</P>

Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study

Keystone, E C,Genovese, M C,Klareskog, L,Hsia, E C,Hall, S T,Miranda, P C,Pazdur, J,Bae, S-C,Palmer, W,Zrubek, J,Wiekowski, M,Visvanathan, S,Wu, Z,Rahman, M U BMJ Publishing Group 2009 Annals of the Rheumatic Diseases Vol.68 No.6

<P><B>Objective:</B></P><P>The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy.</P><P><B>Methods:</B></P><P>Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n  =  133), golimumab 100 mg injections plus placebo capsules (group 2, n  =  133), golimumab 50 mg injections plus methotrexate capsules (group 3, n  =  89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n  =  89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24.</P><P><B>Results:</B></P><P>The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively.</P><P><B>Conclusion:</B></P><P>The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.</P>

Role of allostatic load and health behaviours in explaining socioeconomic disparities in mortality: a structural equation modelling approach

Kim, Gyu Ri,Jee, Sun Ha,Pikhart, Hynek BMJ Publishing Group Ltd 2018 Journal of epidemiology & community health Vol.72 No.6

<P>Conclusions Our findings provide support for the mediating role of AL and health behaviours in the link between SEP and mortality. Policies designed to reduce social disparities in mortality in the long term should primarily focus on reducing stress and promoting healthy lifestyles among the socially disadvantaged groups. Future studies should further assess the role of other mediators such as psychosocial factors, which may contribute to socioeconomic inequalities in mortality.</P>

Extrastriatal dopaminergic changes in Parkinson’s disease patients with impulse control disorders

Lee, Jee-Young,Seo, Seong Ho,Kim, Yu Kyeong,Yoo, Hye Bin,Kim, Young Eun,Song, In Chan,Lee, Jae Sung,Jeon, Beom S BMJ Publishing Group Ltd 2014 Journal of neurology, neurosurgery and psychiatry Vol.85 No.1

<P><B>Objective</B></P><P>To investigate the extrastriatal dopaminergic neural changes in relation to the medication-related impulse control disorders (ICD) in Parkinson's disease (PD).</P><P><B>Method</B></P><P>A total of 31 subjects (11 and 11 drug-treated PD patients with and without medication-related ICDs and 9 healthy controls) having no other co-morbid psychiatric disorders participated in this study. Each subject underwent dynamic <I>N</I>-(3-[<SUP>18</SUP>F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography scans. Binding potentials (BP) at nucleus accumbens, amygdala, orbitofrontal and ventromedial prefrontal cortex (VMPFC), putamen and caudate nucleus were estimated, and whole brain parametric maps of [<SUP>18</SUP>F]-FP-CIT binding were analysed by original and putaminal normalised manners.</P><P><B>Results</B></P><P>Compared with the healthy controls, BPs at both VMPFCs were significantly high and the extrastriatal to putaminal BP ratios at all regions were approximately three times higher in both PD groups. The PD ICD patients showed significantly higher BPs at the right VMPFC and tendency to lower BPs at the left nucleus accumbens compared with those free of ICD. The ICD subjects also showed reduced uptakes at both ventral striatal regions in the original parametric analysis and higher uptakes at the left insular and right posterior cingulate cortex and lower uptakes at both ventral pallidums in the putaminal normalised parametric analysis compared with the non-ICD subjects.</P><P><B>Conclusions</B></P><P>A great gap in extrastriatal versus striatal dopaminergic fibre degenerations is an intrinsic condition predisposing to ICD in PD. Distinct pattern of extrastriatal changes between the ICD and non-ICD patients could provide a further insight into a mechanism of ICD in PD.</P>