婦人科手術術後の症候性肺血栓塞栓症予防スクリーニングの有用性についての検討

OBJECTIVE: To evaluate a sequential screening method's efficacy in predicting symptomatic pulmonary thromboembolism (PTE) after gynecologic surgery. METHODS: A prospective study employing a two-stage screening process was conducted among consecutive asymptomatic adults who underwent outpatient evaluation for gynecologic surgery at Nara Medical University Hospital, Japan, between April 1, 2004, and December 31, 2013. Patients with a preoperative plasma D-dimer level greater than or equal to 1.0μg/mL underwent compression ultrasonography of the lower extremities. The primary outcome measure was postoperative detection of symptomatic PTE. RESULTS: Overall, 1729 patients were included. The mean D-dimer level was 1.7±3.3μg/mL. Compression ultrasonography was conducted among 470 (27.1%) patients with positive D-dimer test results; symptomatic deep vein thrombosis (DVT) was preoperatively detected among 94 (20.0%) of them. Patients with DVT (n=94) had higher D-dimer levels than patients (n=1635) without (7.8±12.8μg/mL vs 1.1±1.8μg/mL; P<0.001). Despite anticoagulant therapy, symptomatic PTE was detected postoperatively among two of these 94 patients. Symptomatic PTE was also detected among four of 376 patients with positive D-dimer test results but no evidence of DVT by ultrasonography. No clinical onset of postoperative PTE was observed among 1259 patients with D-dimer levels below the cut-off value. CONCLUSION: The PROVEN screening strategy (Preoperative surveillance using a sequential strategy) was ineffective at predicting postoperative symptomatic PTE.博士（医学）・乙第1375号・平成28年3月15日Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved

Induced Cooperation to Access a Shareable Reward Increases the Hierarchical Segregation of Wild Vervet Monkeys

Until now cooperation experiments in primates have paid little attention to how cooperation can emerge and what effects are produced on the structure of a social group in nature. I performed field experiments with three groups of wild vervet monkeys in South Africa. I induced individuals to repeatedly approach and operate food containers. At least two individuals needed to operate the containers in order to get the reward. The recurrent partner associations observed before the experiment only partly predicted the forming of cooperative partnerships during the experiment. While most of the tested subjects cooperated with other partners, they preferred to do so with specific combinations of individuals and they tended not to mix with other group members outside these preferred partnerships. Cooperation therefore caused the relatively homogeneous networks I observed before the experiment to differentiate. Similar to a matching market, the food sharing partners selected each other limiting their choice. Interestingly neither sex nor age classes explained the specific partner matching. Kinship could not explain it either. Rather, higher ranking individuals cooperated with other higher ranking individuals, and lower ranking also matched among the same rank. This study reveals the key role dominance rank plays when food resources are patchy and can only be accessed through sharing with other individuals

Assessment of funnel plot asymmetry and publication bias in reproductive health meta-analyses: an analytic survey

BACKGROUND: Despite efforts to assure high methodological standards, systematic reviews may be affected by publication bias. The objective of this study was to evaluate the occurrence of publication bias in a collection of high quality systematic reviews on reproductive health. METHODS: Systematic reviews included in the Reproductive Health Library (RHL), issue No 9, were assessed. Funnel plot was used to assess meta-analyses containing 10 or more trials reporting a binary outcome. A funnel plot, the estimated number of missing studies and the adjusted combined effect size were obtained using the "trim and fill method". Meta-analyses results that were not considered to be robust due to a possible publication bias were submitted to a more detailed assessment. RESULTS: A total of 21 systematic reviews were assessed. The number of trials comprising each one ranged from 10 to 83 (median = 13), totaling 379 trials, whose results have been summarized. None of the reviews had reported any evaluation of publication bias or funnel plot asymmetry. Some degree of asymmetry in funnel plots was observed in 18 of the 21 meta-analyses evaluated (85.7%), with the estimated number of missing studies ranging from 1 to 18 (median = 3). Only for three meta-analyses, the conclusion could not be considered robust due to a possible publication bias. CONCLUSION: Asymmetry is a frequent finding in funnel plots of meta-analyses in reproductive health, but according to the present evaluation, less than 15% of meta-analyses report conclusions that would not be considered robust. Publication bias and other sources of asymmetry in funnel plots should be systematically addressed by reproductive health meta-analysts. Next amendments in Cochrane systematic reviews should include this type of evaluation. Further studies regarding the evolution of effect size and publication bias over time in systematic reviews in reproductive health are needed

PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation

BACKGROUND AND OBJECTIVES: Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted. DESIGN AND SETTING: A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites). PARTICIPANTS AND INTERVENTIONS: Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks). MAIN OUTCOME MEASURES: Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use. METHODS: Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth. RESULTS: A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15; p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence's threshold of £20,000-30,000 per quality-adjusted life-year as between 0.7145 and 0.7341. CONCLUSIONS: There is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM. LIMITATIONS: This study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle. FUTURE WORK: Future research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 41. See the NIHR Journals Library website for further project information

Feedback models for gambling control: the use and efficacy of online responsible gambling tools

Social responsibility in gambling has become a major issue for the gaming industry. This has been coupled with the rise of behavioural tracking technologies that allow companies to track every behavioural decision and action made by gamblers on online gambling sites, slot machines, and/or any type of gambling that utilizes player cards. This chapter has a number of distinct but related aims including: (a) a brief overview of behavioral tracking technologies accompanied by a critique of both advantages and disadvantages of such technologies for both the gaming industry and researchers; and (b) results from a series of studies completed using behavioral tracking data to evaluate the efficacy of online responsible gambling tools (particularly in relation to data concerning the use of social responsibility tools such as limit setting, pop-up messaging, and personalized feedback to gamblers)

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease

Are TNF‐α blockers effective and safe for Kawasaki disease in children? A Cochrane Review summary with commentary

The aim of this commentary is to discuss the published Cochrane Review “TNF-α blockers for the treatment of Kawasaki disease in children1” by Yamaji et al.,a under the direct supervision of Cochrane Review Group. This Cochrane Corner is produced in agreement with the International Journal of Rheumatic Diseases by Cochrane Rehabilitatio