bluuebunny/crossref_metadata_2025 huggingface dataset:
Gefapixant in two randomised dose-escalation studies in chronic cough
Authors: Smith Jaclyn A. , Kitt Michael M. , Butera Peter , Smith Steven A. , Li Yuping , Xu Zhi Jin , Holt Kimberley , Sen Shilpi , Sher Mandel R. , Ford Anthony P.
Published: January 2020

Background and objectives

Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach.

Materials and methods

Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50–200 mg, study 2: 7.5–50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.

Results

In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg.

Conclusions

P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.
Genetic susceptibility to asthma increases the vulnerability to indoor air pollution
Authors: Hüls Anke , Vanker Aneesa , Gray Diane , Koen Nastassja , MacIsaac Julia L. , Lin David T.S. , Ramadori Katia E. , Sly Peter D. , Stein Dan J. , Kobor Michael S. , Zar Heather J.
Published: January 2020

Introduction

Indoor air pollution and maternal smoking during pregnancy are associated with respiratory symptoms in infants, but little is known about the direct association with lung function or interactions with genetic risk factors. We examined associations of exposure to indoor particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM10) and maternal smoking with infant lung function and the role of gene–environment interactions.

Methods

Data from the Drakenstein Child Health Study, a South African birth cohort, were analysed (n=270). Lung function was measured at 6 weeks and 1 year of age, and lower respiratory tract infection episodes were documented. We measured pre- and postnatal PM10exposures using devices placed in homes, and prenatal tobacco smoke exposure using maternal urine cotinine levels. Genetic risk scores determined from associations with childhood-onset asthma in the UK Biobank were used to investigate effect modifications.

Results

Pre- and postnatal exposure to PM10as well as maternal smoking during pregnancy were associated with reduced lung function at 6 weeks and 1 year as well as with lower respiratory tract infection in the first year. Due to a significant interaction between the genetic risk score and prenatal exposure to PM10, infants carrying more asthma-related risk alleles were more susceptible to PM10-associated reduced lung function (pinteraction=0.007). This interaction was stronger in infants with Black African ancestry (pinteraction=0.001) and nonexistent in children with mixed ancestry (pinteraction=0.876).

Conclusions

PM10and maternal smoking exposures were associated with reduced lung function, with a higher susceptibility for infants with an adverse genetic predisposition for asthma that also depended on the infant's ancestry.
Potential impacts of a novel integrated extracorporeal-CPR workflow using an interventional radiology and immediate whole-body computed tomography system in the emergency department
Authors: Hayashida Kei , Kinoshita Takahiro , Yamakawa Kazuma , Miyara Santiago J. , Becker Lance B. , Fujimi Satoshi
Published: January 2020

Extracorporeal cardiopulmonary resuscitation (ECPR) can be associated with increased survival and neurologic benefits in selected patients with out-of-hospital cardiac arrest (OHCA). However, there remains insufficient evidence to recommend the routine use of ECPR for patients with OHCA. A novel integrated trauma workflow concept that utilizes a sliding computed tomography (CT) scanner and interventional radiology (IR) system, named a hybrid emergency room system (HERS), allowing emergency therapeutic interventions and CT examination without relocating trauma patients, has recently evolved in Japan. HERS can drastically shorten the ECPR implementation time and more quickly facilitate definitive interventions than the conventional advanced cardiovascular life support workflow. Herein, we discuss our novel workflow concept using HERS on ECPR for patients with OHCA.
Mycoplasma pneumoniae pneumonia associated thrombosis at Beijing Children’s hospital
Authors: Liu Jinrong , He Ruxuan , Wu Runhui , Wang Bei , Xu Hui , Zhang Yue , Li Huimin , Zhao Shunying
Published: January 2020

Background

With the increase of awareness ofmycoplasma pneumoniaepneumonia (MPP), we found thrombosis in severe MPP (SMPP) was not rare. The aim of the study was to investigate the clinical characteristics, treatment, and long-term prognosis of MPP-associated thrombosis.

Methods

We retrospectively reviewed the medical records of 43 children with MPP-associated thrombosis between January 2013 and June 2019 at Beijing Children’s Hospital. The results of blood coagulation studies, autoimmune antibody, thrombophilia screening, contrast-enhanced lung computed tomography, echocardiography, and blood vessel ultrasonography were analyzed, as were treatment outcomes.

Results

Forty-two patients were diagnosed with SMPP. D-dimer was higher than 5.0 mg/L in 58.1% (25/43) of patients. The mean D-dimer level was 11.1 ± 12.4 mg/L. Anticardiolipin-IgM was positive in 60.0% of patients, β2-glycoprotein-IgM in 64.0%, and lupus anticoagulant in 42.1%. Chest imaging revealed pulmonary consolidation with lobe distribution in all patients (2/3–1 lobe in 10 patients, > 1 lobe in 29 patients). In our experience, thrombosis can occur in a vessel of any part of the body, and it can be initially detected as late as 31 days after disease onset. Thrombosis in the brain and abdomen can occur early, at 5 days after disease onset. Pulmonary vessels were the most commonly involved sites in the current study, and accordingly chest pain was the most common symptom (32.6%), followed by neurological symptoms (14.0%) and abdominal pain (9.3%). Thirty-five percent of patients were asymptomatic with regard to thrombosis. All patients underwent anticoagulant therapy, and thrombus absorption took > 3 months in most patients. All patients were followed until October 2019, at which time 41 were asymptomatic and 2 had mild recurrent cough.

Conclusions

SMPP with pulmonary consolidation (> 2/3 lobe) was the most strongly associated risk factor for thrombosis. Thrombosis-associated symptoms may be subtle, even absent. Elevated D-dimer, specifically > 11.1 mg/L (even > 5.0 mg/L), would assist in the early diagnosis of thrombosis. The long-term prognosis of thrombosis was good after timely administration of anticoagulant therapy.
Safety and efficacy of direct-acting antivirals for chronic hepatitis C in patients with chronic kidney disease
Authors: Iliescu Elena Laura , Mercan-Stanciu Adriana , Toma Letitia
Published: January 2020

Background

This is a real-world evidence study that aims to analyze the efficacy, tolerability and safety profile of paritaprevir/ombitasvir/ritonavir and dasabuvir, in patients with renal impairment.

Methods

We conducted an observational prospective study, on 232 patients with chronic kidney disease, undergoing treatment with paritaprevir/ombitasvir/ritonavir and dasabuvir, for chronic hepatitis C infection - genotype 1b. Renal and liver function were assessed at the beginning of therapy, monthly during treatment and three months after therapy completion.

Results

All patients achieved sustained virologic response. Common side effects were nausea, fatigue and headache. Close monitoring of tacrolimus blood levels and dose reduction was required in kidney transplant recipients.

Conclusions

HCV therapy in the setting of renal dysfunction has always been a challenging topic. Direct-acting antivirals have shown promising effects, demonstrating good tolerance and efficacy in patients with HCV infection and renal impairment. Sustained virologic response within our study population was 100%.
The prediction of acute ischemic stroke patients’ long-term functional outcomes treated with bridging therapy
Authors: Chang Yu-Jun , Liu Chi-Kuang , Wu Wen-Pei , Wang Shih-Chun , Chen Wei-Liang , Lin Chih-Ming
Published: January 2020

Background

Intravenous thrombolysis therapy (IVT) bridged with intra-arterial thrombectomy (IAT) has recently been recommended as favorable treatment option to ensure that the thrombolytic effect is delivered to the affected region for acute ischemic stroke patients. However, there remains a lack of studies reporting outcome prediction in this group of patients. In this study, we aimed to identify indicators from baseline data that could be used for early prediction of long-term functional outcomes.

Methods

This retrospective single center cohort study included acute ischemic stroke (AIS) patients (n = 92) who received IVT and IAT. Functional outcomes were assessed by the National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index. We investigated the relationship between functional outcomes at one-year post-procedure and potential predictors such as occlusion site, modified thrombolysis in cerebral infarction (mTICI) score following the IVT/IAT procedure, and degree of stenosis measured by carotid duplex.

Results

67.4% of the studied patients had satisfactory outcomes with mTICI grades of 2b or 3. From baseline to one-year post-procedure, the NIHSS score improved in 88.0%, the mRS score improved in 69.6%, and the Barthel index improved with 59.8%. Patients with internal carotid artery (ICA) or vertebral artery (VA) stenosis detected by carotid duplex had significantly poorer functional outcomes, measured by the mRS score and Barthel index. In patients with a satisfactory mTICI grade, improvement in the mRS score was only observed in 60.0% of patients with ICA stenosis, compared to 93.8% without ICA stenosis. The VA stenosis was the most significant factor associated with the improvement of mRS (OR = 0.08; 95% CI: 0.01–0.63; P = 0.017) and Barthel Index (OR = 0.06; 95% CI: 0.01–0.47; P = 0.008) in multiple regression analysis.

Conclusions

ICA or VA stenosis detected by carotid duplex could serve as predictors of significantly poorer functional outcomes in stroke patients treated with bridging therapy; they might be useful clinical markers, particularly as stenosis could be detected by a non-invasive and portable method.
GC-PROM: validation of a patient-reported outcomes measure for Chinese patients with gastric cancer
Authors: Hu Xiaojuan , Zhao Fen , Yu Hongmei , Luo Yanhong , Liu Jinchun , Zhang Yanbo
Published: January 2020

Background

There is increasing recognition that PROs are important in the estimation of the burden of long-term survival among patients with gastric cancer. The study aimed to develop a disease-specific instrument to assess patient-reported outcomes for Chinese patients with gastric cancer.

Method

Following the FDA’s draft guidance for patient-reported outcome, conceptual framework and item pool were defined based on relevant existing work. A draft scale was formed after revising some items based on feedback from experts and Chinese patients with gastric cancer. The pre-survey and formal survey were conducted in eight different hospitals in Shanxi Province, and two item-selection process based on classical test theory and item response theory. Finally, the patient-reported outcomes measure for Chinese patients with gastric cancer (GC-PROM) was validated in terms of reliability, validity, and feasibility. The minimal clinically important difference was determined by distribution-based method.

Results

The final GC-PROM consisted of 38 items, 13 subdomains, and 4 domains. Reliability was verified by Cronbach’s alpha coefficient for four domains and 13 subdomains respectively. The validity results showed that the multidimensional scale fulfilled expectations. In the formal survey, the completion rate was 96.16%, and the average filling time was less than half an hour. The values of the minimal clinically important difference were 4.14, 3.41, 3.37, and 3.28 in the four domains.

Conclusions

The GC-PROM had good reliability, validity, and feasibility and thus can be considered an effective clinical evaluation instrument for Chinese patients with gastric cancer.
Cleidocranial dysplasia with growth hormone deficiency: a case report
Authors: Takaki Nozomi , Mori Jun , Matsuo Satoshi , Osamura Toshio , Michigami Toshimi
Published: January 2020

Background

Cleidocranial dysplasia (CCD) is a rare skeletal disorder with autosomal dominant inheritance that is characterized by hypoplastic clavicles, delayed closure of the cranial sutures, dental abnormalities, and short stature, among other features. The responsible gene for CCD is RUNX2 located on the short arm of chromosome 6p21. In general, there are intrafamilial variations in height among CCD patients. Few studies have reported data on recombinant human growth hormone (rhGH) treatment for patients with CCD; thus, it remains to be elucidated whether rhGH treatment can improve short stature. Here, we report a case of a 6-year-old girl with CCD who has growth hormone deficiency (GHD) and a novel mutation of RUNX2.

Case presentation

At 5 years of age, this patient was diagnosed with GHD and rhGH treatment was initiated. Thereafter, she was diagnosed with CCD due to the presence of hypoplastic clavicles and an open fontanelle, which was also observed in her mother and brother. She responded well to rhGH treatment; her height improved from − 3.2 SD to − 2.4 SD after 13 months.

Conclusion

A detailed patient history and physical examination are necessary for the early diagnosis of CCD. Similarly, to ascertain the effect of rhGH treatment, careful evaluation of the patient’s final height post-therapy is needed.
Computer-assisted preoperative planning improves the learning curve of PFNA-II in the treatment of intertrochanteric femoral fractures
Authors: Wang Dongdong , Zhang Kun , Qiang Minfei , Jia Xiaoyang , Chen Yanxi
Published: January 2020

Background

Intertrochanteric femoral fractures are prevalent among the elderly, and usually demands surgical treatments. Proximal femoral nail antirotation Asian version (PFNA-II) is widely used for intertrochanteric fracture treatment. The computer-assisted preoperative planning (CAPP) system has the potential to reduce the difficulty of PFNA-II in the treatment of intertrochanteric fractures. The aim of the study was to investigate and compare the learning curves of PFNA-II treatment with CAPP and conventional preoperational planning methods for intertrochanteric femoral fractures.

Methods

A total of 125 patients with intertrochanteric fracture who were treated with PFNA-II between March 2012 and June 2015 were retrospectively analyzed. Patients who underwent surgery with CAPP procedure by a junior surgeon were regarded as group A (n = 53); patients who underwent the conventional surgery by another junior surgeon were regarded as group B (n = 72). Each group was divided into three subgroups (case 1–20, case 21–40, case 41–53 or case 41–72).

Results

The average operation time of group A was 45.00(42.00, 50.00) minutes, and in group B was 55.00 (50.00, 60.00) minutes (P < 0.01). Average radiation frequency and blood loss were 13.02 ± 2.32, 160.00 (140.00, 170.00) ml and 20.92 ± 3.27, 250.00 (195.00, 279.50) ml, respectively, with significant differences (P < 0.01). The learning curve of the surgical procedure in group A was steeper than that in group B. There were no significant differences in patient reported outcomes, hospital stay and complication rate between the two groups. Significant differences were observed between group A and B in Harris score at last follow-up in the AO/OTA type 31-A2 intertrochanteric fracture (P < 0.05).

Conclusion

Compared with conventional preoperative planning methods, CAPP system significantly reduced operation time, radiation frequency and blood loss, thus reshaped the learning curve of PFNA-II treatment with lower learning difficulty.

Trial registration

researchregistry4770. Registered 25 March 2019.
An extremely rare case of lesser omental hernia in an elderly female patient following total colectomy
Authors: Liu Zhicheng , He Liang , Jiao Yan , Xu Zhonghang , Suo Jian
Published: January 2020

Background

An intro-abdominal hernia through the lesser omentum is a rare but severe condition that can cause intestinal obstruction and other life-threating complications. Until now, only a handful of cases have been reported worldwide. The diagnosis of lesser omental hernia remains challenging for emergency surgeons because of the unspecific symptoms. Therefore, there is a need for a better understanding of the characteristics of this condition.

Case presentation

In this report, we described the case of a 73-year-old female patient who was diagnosed with a lesser omental hernia caused by previous total colectomy. The patient underwent emergency surgery, and the intraoperative findings revealed a 200-cm segment of the small intestine was herniated through a defected lesser omentum (approximately 3 × 4 cm) from the lesser retrogastric curvature of the stomach. Besides, we summarize the specific abdominal computed tomography (CT) findings of lesser omental hernia by reviewing the literature.

Conclusion

The lesser omental hernia is extremely rare but can cause serious complications. The cause of lesser omental hernia can be congenital or acquired. Careful examination of the small omentum before the closure of the abdomen is expected to reduce the occurrence of these abdominal surgery-associated complications. The specific features of abdominal CT in cases of lesser omental hernia, which are summarized in this article, can help other clinicians to obtain accurate diagnoses of lesser omentum hernia in the future.
A meta-ethnography to understand the experience of living with urinary incontinence: ‘is it just part and parcel of life?’
Authors: Toye Francine , Barker Karen L.
Published: January 2020

Background

Urinary incontinence (UI) is highly prevalent and affects the lives of many men and women. We aimed to conduct a qualitative evidence synthesis (QES) to explore the experience of living with UI and to develop a conceptual model that can help us to understand this experience, and the potential barriers to appropriate healthcare.

Methods

We used the methods of meta-ethnography developed by Noblit and Hare and recently refined for larger studies. Meta-ethnography involves identifying concepts from the studies and abstracting these concepts into a line of argument. We searched for studies that explored the experience of adults with UI. We used the GRADE-CERQual framework to assess confidence in review findings.

Results

We screened 2307 titles, 429 abstracts, 107 full texts and included 41 studies (36 unique samples) in the synthesis. We organised the concepts into 26 conceptual categories, which we further abstracted into 6 themes: (1) Am I ill or is this normal? (2) It effects who I am and how I feel; (3) I feel stigmatised, ashamed and guilty; (4) talking can be difficult but it can help; (5) keeping incontinence under control; (6) have I got to the point that I need help? Our model conceptualises living with UI as navigating antagonists: Is UI normal or am I ill? Do I need help or am I managing? Do I keep UI to myself (and manage alone) or do I tell other people (and get the support that I need)? Do I use control strategies that focus on concealing (avoid risky situations, wear pads) versus, I use strategies that focus on improving the bodily function to improve continence. Our model highlights the experience of stigma, shame and guilt which exert a pull towards concealment.

Conclusions

The culture of secrecy and profound sense of shame is barrier to seeking help. An environment which reduces the shame and stigma of UI may help people to switch the focus to strategies that will improve continence, rather than conceal incontinence.
Peers as OSCE assessors for junior medical students – a review of routine use: a mixed methods study
Authors: Schwill Simon , Fahrbach-Veeser Johanna , Moeltner Andreas , Eicher Christiane , Kurczyk Sonia , Pfisterer David , Szecsenyi Joachim , Loukanova Svetla
Published: January 2020

Background

Peer-assisted learning is well established in medical education; however, peer tutors rarely act as assessors for the OSCE. In the compulsory, near-peer teaching programme covering basic medical skills at the University of Heidelberg, peer tutors serve as assessors on a formative OSCE. This study aimed to investigate the feasibility and acceptance of peer assessors and to survey the perceived advantages and disadvantages of their use.

Methods

In 2016 and 2017 all OSCE peer assessors (third to sixth-year medical students) and all of the peer-assessed students in 2017 (second-year-medical students) were invited to participate in a survey. Both groups were asked to complete a tablet-based questionnaire immediately after the OSCE. Peer assessors were asked to rate eight statements and the peer-assessed students to rate seven statements on a five-point Likert scale. Both were asked to comment on the advantages and disadvantages of peer-assessors.

Results

Overall, 74 of 76 peer assessors and 307 of 308 peer-assessed students participated in the study. 94% (67/74) of peer assessors and 90% (276/307) of the peer-assessed group thought that it is important to have peer tutors as assessors. Of the peer assessors, 92% (68/74) felt confident in giving structured feedback during the OSCE and 66% (49/74) felt they had improved their teaching skills. Of the peer-assessed students, 99% (306/307) were satisfied with their peers as OSCE assessors and 96% (292/307) considered the peer feedback during the OSCE as helpful. The participants mentioned structural benefits, such as lower costs, and suggested the quality of the OSCE was higher due to the use of peer assessors. The use of peer assessors was found to be beneficial for the learners in the form of high-quality feedback and an overall reduction in stress. Furthermore, the use of peer assessors was found to be beneficial for the peer assessors (improved teaching and clinical skills).

Conclusion

From a learner’s perspective, the use of peer assessors for a formative OSCE that is part of a near-peer teaching program aimed at junior medical students is favourable for all. A broad implementation of peer assessment in the formative OSCE should be encouraged to investigate effects on quality and stress-reduction.
Correction to: The predictive value of dynamic monitoring of peripheral blood lymphocyte to monocyte ratio in patients with extranodal NK/T cell lymphoma
Authors: Zhang Shengnan , Li Mengjuan , Yuan Fangfang , Chen Lin , Mi Ruihua , Wei Xudong , Song Yongping , Yin Qingsong
Published: January 2020

After publication of our article [1] it was highlighted by the authors that the type of this article was primary research, instead of review.
The complex microbiome from native semen to embryo culture environment in human in vitro fertilization procedure
Authors: Štšepetova Jelena , Baranova Juliana , Simm Jaak , Parm Ülle , Rööp Tiiu , Sokmann Sandra , Korrovits Paul , Jaagura Madis , Rosenstein Karin , Salumets Andres , Mändar Reet
Published: January 2020

Background

Only a few microbial studies have conducted in IVF (in vitro fertilization), showing the high-variety bacterial contamination of IVF culture media to cause damage to or even loss of cultured oocytes and embryos. We aimed to determine the prevalence and counts of bacteria in IVF samples, and to associate them with clinical outcome.

Methods

The studied samples from 50 infertile couples included: raw (n = 48), processed (n = 49) and incubated (n = 50) sperm samples, and IVF culture media (n = 50). The full microbiome was analyzed by 454 pyrosequencing and quantitative analysis by real-time quantitative PCR. Descriptive statistics, t-, Mann-Whitney tests and Spearman’s correlation were used for comparison of studied groups.

Results

The study involved normozoospermic men. Normal vaginal microbiota was present in 72.0% of female partners, while intermediate microbiota and bacterial vaginosis were diagnosed in 12.0 and 16.0%, respectively. The decreasing bacterial loads were found in raw (35.5%), processed (12.0%) and sperm samples used for oocyte insemination (4.0%), and in 8.0% of IVF culture media. The most abundant genera of bacteria in native semen and IVF culture media were Lactobacillus, while in other samples Alphaproteobacteria prevailed. Staphylococcus sp. was found only in semen from patients with inflammation. Phylum Bacteroidetes was in negative correlation with sperm motility and Alphaproteobacteria with high-quality IVF embryos.

Conclusion

Our study demonstrates that IVF does not occur in a sterile environment. The prevalent bacteria include classes Bacilli in raw semen and IVF culture media, Clostridia in processed and Bacteroidia in sperm samples used for insemination. The presence of Staphylococcus sp. and Alphaproteobacteria associated with clinical outcomes, like sperm and embryo quality.
Knowledge of obstetric danger signs and associated factors: a study among mothers in Shashamane town, Oromia region, Ethiopia
Authors: Wassihun Biresaw , Negese Berhanu , Bedada Hunduman , Bekele Solomon , Bante Agegnehu , Yeheyis Tomas , Abebe Agere , uli Duro , Mohammed Merima , Gashawbez Salasebish , Hussen Emebet
Published: January 2020

Background

Child birth which is a special moment for parents, families and communities is also a time of intense vulnerability. In many developing countries including Ethiopia, maternal morbidity and mortality still pose a substantial burden. Raising awareness of women about the danger signs of pregnancy and childbirth is the first essential step in appropriate and timely obstetric care.

Objective

To assess the knowledge of obstetric danger signs among mothers and associated factors in Shashamane town, oromia region, Ethiopia.

Methods

A community based cross sectional study design was employed. All kebeles were included in study; the number of households was determined using proportionate-to-population size then systematic random sampling technique to select 422 women who gave birth in Shashamane town between April and May 2018. A structured questionnaire was used to collect data. Data was checked and entered into Epi data version 3.1 then exported to Statistical Package for Social Science version 23 for analysis. Univariate, bivariate and multivariable analysis with 95% CI was carried out. Women who spontaneously mentioned at least two danger signs of pregnancy from eight items were considered to have good knowledge of the obstetric danger signs.

Result

A total of 422 mothers were involved in the study. The mean age of the respondent was 25 with a standard deviation of 4.3 year. 59.5% of the respondents were found to have poor knowledge of obstetric danger signs. Majority of respondents mentioned vaginal bleeding (64.7%) as a danger sign of pregnancy. According to the result of the multivariable analysis, antenatal care was significantly associated with the knowledge of obstetric danger sign. Respondents who attended antenatal care were 1.26 times more likely to have good knowledge of obstetric danger signs than those who had no antenatal care [AOR = 1.26, 95%CI (1.08–1.85)]. Respondents who gave birth at health center were 3.57 time more likely to have good knowledge of obstetric danger signs than those who gave birth at home [AOR = 3.57, 95%CI (1.23–10.39)].

Conclusion

According to this study, the knowledge of obstetric danger signs was poor. Some of the factors associated with this knowledge were antenatal care attendance and place of delivery; therefore, it is recommended that mothers should have at least four antenatal visits; this may create good relationship with the providers and enhance their knowledge. In addition to this providing compassionate and respectful maternity care in health facility is also crucial steps to attract more women to health facilities, and to reduce home deliveries.
First-in-human phase I study of BPI-9016M, a dual MET/Axl inhibitor, in patients with non-small cell lung cancer
Authors: Hu Xingsheng , Zheng Xin , Yang Sheng , Wang Lin , Hao Xuezhi , Cui Xinge , Ding Lieming , Mao Li , Hu Pei , Shi Yuankai
Published: January 2020

Background

BPI-9016M is a novel small-molecule inhibitor that simultaneously targets both c-Met and AXL tyrosine kinases. This phase I study aimed to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of BPI-9016M in Chinese patients with advanced non-small cell lung cancer (NSCLC).

Methods

Over the dose range of 100 mg to 800 mg, eligible patients were administered with a single dose of 9016M tablet and received 7 days of pharmacokinetics evaluation, followed by continuous dose administration (QD dosing, 28 days). Standard “3 + 3” dose escalations were performed.

Results

Twenty NSCLC patients were treated. All patients experienced at least one adverse event (AE), of which treatment-related adverse events (TRAEs) were reported in 17 (85.0%) patients. The most common TRAEs were alanine transaminase (ALT) elevation (60%), bilirubin increased (40%), dysgeusia (40%), constipation (30%), hypertension (25%), and palmar-plantar erythrodysesthesia syndrome (15%). The TRAEs of grade 3 or higher during treatment were hypertension (15%), pulmonary embolism (5%), and laryngeal pain (5%). No dose-limiting toxicity (DLT) was observed, and the MTD was not reached. The median time to Cmax ranged from 2.0 to 3.5 h, and the plasma concentration of BPI-9016M declined rapidly after Tmax fitting a single-compartment model. The mean AUC0–72 h of M1 and M2-2, main metabolites of BPI-9016M, were 4.8–6.6 folds and 4.1–9.8 folds higher than that of BPI-9016M, respectively. Exposure to BPI-9016M, M1, and M2-2 reached moderate saturation at 600 mg. Among 19 evaluable patients, 1 had a partial response and 10 patients had stable disease.

Conclusion

BPI-9016M showed favorable safety and pharmacokinetic profiles, and no DLT was observed at doses up to 800 mg once daily. The promising antitumor activity in Chinese NSCLC patients supports further development of this tyrosine kinase inhibitor.

Trial registration

Clinical Trial ID: NCT02478866, registered May 21, 2015.
Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
Authors:   GENEPSO, Mavaddat Nasim ,   EMBRACE,   HEBON,   kConFab Investigators,   on behalf of IBCCS,   kConFab,   BCFR, Antoniou Antonis C. , Mooij Thea M. , Hooning Maartje J. , Heemskerk-Gerritsen Bernadette A. , Noguès Catherine , Gauthier-Villars Marion , Caron Olivier , Gesta Paul , Pujol Pascal , Lortholary Alain , Barrowdale Daniel , Frost Debra , Evans D. Gareth , Izatt Louise , Adlard Julian , Eeles Ros , Brewer Carole , Tischkowitz Marc , Henderson Alex , Cook Jackie , Eccles Diana , van Engelen Klaartje , Mourits Marian J. E. , Ausems Margreet G. E. M. , Koppert Linetta B. , Hopper John L. , John Esther M. , Chung Wendy K. , Andrulis Irene L. , Daly Mary B. , Buys Saundra S. , Benitez Javier , Caldes Trinidad , Jakubowska Anna , Simard Jacques , Singer Christian F. , Tan Yen , Olah Edith , Navratilova Marie , Foretova Lenka , Gerdes Anne-Marie , Roos-Blom Marie-José , Van Leeuwen Flora E. , Arver Brita , Olsson Håkan , Schmutzler Rita K. , Engel Christoph , Kast Karin , Phillips Kelly-Anne , Terry Mary Beth , Milne Roger L. , Goldgar David E. , Rookus Matti A. , Andrieu Nadine , Easton Douglas F.
Published: January 2020

Background

The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk forBRCA1andBRCA2mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly forBRCA2mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.

Methods

A multi-centre prospective cohort of 2272BRCA1and 1605BRCA2mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.

Results

There was no association between RRSO and breast cancer forBRCA1(HR = 1.23; 95% CI 0.94–1.61) orBRCA2(HR = 0.88; 95% CI 0.62–1.24) mutation carriers. ForBRCA2mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR forBRCA2mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.

Conclusion

We found no evidence that RRSO reduces breast cancer risk forBRCA1mutation carriers. A potentially beneficial effect forBRCA2mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers
Authors: Egorova Olga , Myte Robin , Schneede Jörn , Hägglöf Bruno , Bölte Sven , Domellöf Erik , Ivars A’roch Barbro , Elgh Fredrik , Ueland Per Magne , Silfverdal Sven-Arne
Published: January 2020

Background

Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis.

Methods

Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation.

Results

We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22–2.37, FDR adjustedP= 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring.

Conclusions

Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.
An edge computing framework based on OFDM radar for low grazing angle target tracking
Authors: Karimi Vahid , Mohseni Reza , Khosravi Mohammad R.
Published: January 2020

In this paper, a novel adaptive algorithm to detect and track targets with low grazing angle is addressed. For this purpose, an orthogonal frequency division multiplexing (OFDM) radar signal is employed through an edge computing framework over the radar platform. However, detecting the targets in the low grazing angle area is a great challenge due to severe multipath reflection effects. The Earth’s curvature geometry model is presented as the multipath propagation model. Based on the fact that the different scattering centers of a target resonate at different frequencies, we use the optimized OFDM waveform and propose a novel target tracking procedure for low grazing angle target tracking scenarios. The obtained results show that using an OFDM radar waveform provides a more uniform detection coverage in the presence of multipath propagation such that this will fill in the nulls. Finally, simulations are used to compare the performance of the proposed OFDM waveform with the conventional equal-power, the generalized likelihood ratio (GLR)-based and single-carrier waveforms.
Engaging older adults in self-management talk in healthcare encounters: a systematic review protocol
Authors: Lawless Michael T. , Drioli-Phillips Phoebe , Archibald Mandy M. , Kitson Alison L.
Published: January 2020

Background

Clinical practice guidelines for the management of complex chronic conditions in older adults encourage healthcare providers to engage patients in shared decision-making about self-management goals and actions. Yet, healthcare decision-making and communication for this population can pose significant challenges. As a result, healthcare professionals may struggle to help patients define and prioritise their values, goals, and preferences in ways that are clinically and personally meaningful, incorporating physical functioning and quality of life, when faced with numerous diagnostic and treatment alternatives. The aim of this systematic review is to locate and synthesise a body of fine-grained observational research on communication between professionals, older adults, and carers regarding self-management in audio/audio-visually recorded naturalistic interactions.

Methods/design

The paper describes a systematic review of the published conversation analytic and discourse analytic research, using an aggregative thematic approach and following the PRISMA-P guidelines. This review will include studies reporting on adult patients (female or male) aged ≥ 60 years whose consultations are conducted in English in any healthcare setting and stakeholders involved in their care, e.g. general practitioners, nurses, allied health professionals, and family carers. We will search nine electronic databases and the grey literature and two independent reviewers will screen titles and abstracts to identify potential studies. Discrepancies will be resolved via consultation with the review team. The methodological quality of the final set of included studies will be appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research and a detailed description of the characteristics of the included studies using a customised template.

Discussion

This is the first systematic review to date to locate and synthesise the conversation analytic research on how healthcare professionals raise and pursue talk about self-management with older adults in routine clinical interactions. Amalgamating these findings will enable the identification of effective and potentially trainable communication practices for engaging older adults in healthcare decision-making about the self-management goals and actions that enable the greatest possible health and quality of life in older adulthood.

Systematic review registration

PROSPERO CRD42019139376
Developing a clinical decision support for opioid use disorders: a NIDA center for the clinical trials network working group report
Authors: Bart Gavin B. , Saxon Andrew , Fiellin David A. , McNeely Jennifer , Muench John P. , Shanahan Christopher W. , Huntley Kristen , Gore-Langton Robert E.
Published: January 2020

There is an urgent need for strategies to address the US epidemic of prescription opioid, heroin and fentanyl-related overdoses, misuse, addiction, and diversion. Evidence-based treatment such as medications for opioid use disorder (MOUD) are available but lack numbers of providers offering these services to meet the demands. Availability of electronic health record (EHR) systems has greatly increased and led to innovative quality improvement initiatives but this has not yet been optimized to address the opioid epidemic or to treat opioid use disorder (OUD). This report from a clinical decision support (CDS) working group convened by the NIDA Center for the Clinical Trials Network aims to converge electronic technology in the EHR with the urgent need to improve screening, identification, and treatment of OUD in primary care settings through the development of a CDS algorithm that could be implemented as a tool in the EHR. This aim is consistent with federal, state and local government and private sector efforts to improve access and quality of MOUD treatment for OUD, existing clinical quality and HEDIS measures for OUD or drug and alcohol use disorders, and with a recent draft grade B recommendation from the US Preventative Services Task Force (USPSTF) for screening for illicit drug use in adults when appropriate diagnosis, treatment and care services can be offered or referred. Through a face-to-face expert panel meeting and multiple follow-up conference calls, the working group drafted CDS algorithms for clinical care felt to be essential for screening, diagnosis, and management of OUD in primary care. The CDS algorithm was reviewed by addiction specialists and primary care providers and revised based on their input. A clinical decision support tool for OUD screening, assessment, and treatment within primary care systems may help improve healthcare delivery to help address the current epidemic of opioid misuse and overdose that has outpaced the capacity of specialized treatment settings. A semi-structured outline of clinical decision support for OUD was developed to facilitate implementation within the EHR. Further work for adaptation at specific sites and for testing is needed.
Dual-label time-resolved fluoroimmunoassay for simultaneous measurement of human epidermal growth factor receptor 2 and human epididymis protein 4 in serum
Authors: Zhang Yi , Wang Ke , Zhao Ying , Fan Jun , Han Tingting , Si Yu-an , Zhou Bin , Zhang Jue , Hu Zhigang , Xie Minhao
Published: January 2020

In this study, a novel dual-label time-resolved fluoroimmunoassay (TRFIA) is described for simultaneous quantification of human epidermal growth factor receptor 2 (HER-2) and human epididymis protein 4 (HE4) in serum to screen gynecologic cancers. A double-antibody sandwich TRFIA was introduced with europium and samarium chelates to simultaneously detect the concentrations of HER-2 and HE4. Under optimal conditions, the proposed method exhibited wide linear ranges for HER-2 of 0.07–500 ng ml−1 and for HE4 of 0.32–1000 pmol l−1 with the average coefficient of variation below 10%. The specificity was satisfied through determining the other common tumor markers. The recovery rates were 94.5% and 96.6% on average for HER-2 and HE4, respectively. Good correlations were observed in clinical samples between developed method and commercial chemiluminescence immunoassay kits. The results demonstrated that dual-label TRFIA for HER-2 and HE4 was rapid and precise, and therefore could have a promising use in large sample detection for gynecological cancer screening.
Evidence for terrane boundaries and suture zones across Southern Mongolia detected with a 2-dimensional magnetotelluric transect
Authors: Comeau Matthew J. , Becken Michael , Käufl Johannes S. , Grayver Alexander V. , Kuvshinov Alexey V. , Tserendug Shoovdor , Batmagnai Erdenechimeg , Demberel Sodnomsambuu
Published: January 2020

Southern Mongolia is part of the Central Asian Orogenic Belt, the origin and evolution of which is not fully known and is often debated. It is composed of several east–west trending lithostratigraphic domains that are attributed to an assemblage of accreted terranes or tectonic zones. This is in contrast to Central Mongolia, which is dominated by a cratonic block in the Hangai region. Terranes are typically bounded by suture zones that are expected to be deep-reaching, but may be difficult to identify based on observable surface fault traces alone. Thus, attempts to match lithostratigraphic domains to surface faulting have revealed some disagreements in the positions of suspected terranes. Furthermore, the subsurface structure of this region remains relatively unknown. Therefore, high-resolution geophysical data are required to determine the locations of terrane boundaries. Magnetotelluric data and telluric-only data were acquired across Southern Mongolia on a profile along a longitude of approximately 100.5° E. The profile extends ~ 350 km from the Hangai Mountains, across the Gobi–Altai Mountains, to the China–Mongolia border. The data were used to generate an electrical resistivity model of the crust and upper mantle, presented here, that can contribute to the understanding of the structure of this region, and of the evolution of the Central Asian Orogenic Belt. The resistivity model shows a generally resistive upper crust (0–20 km) with several anomalously conductive features that are believed to indicate suture zones and the boundaries of tectonic zones. Moreover, their spatial distribution is coincident with known surface fault segments and active seismicity. The lower crust (30–45 km) becomes generally less resistive, but contains an anomalously conductive feature below the Gobi–Altai zone. This potentially agrees with studies that have argued for an allochthonous lower crust below this region that has been relaminated and metamorphosed. Furthermore, there is a large contrast in the electrical properties between identified tectonic zones, due to their unique tectonic histories. Although penetration to greater depths is limited, the magnetotelluric data indicate a thick lithosphere below Southern Mongolia, in contrast to the previously reported thin lithosphere below Central Mongolia.
Circulating Violence and Value
Authors: Cuppini Niccolò
Published: January 2020

In recent years, a new critical scholarship and movement organi-zation that is adopting the lens of logistics has emerged, marked by a profound interdisciplinarity. Powerful voices from a wide spectrum of radical theoretical and political commitments are delineating critical logistics as a field of vitality. This dialogue with Deborah Cowen sums up and expands some of the main interpretative lines of research and action in logistics by insisting on the ways that the revolution in logistics has reshaped work and the conditions of work for those in positions or occupations that may not seem immediately logistical, including quite centrally, in the production process, which Cowen suggests are inextricable from logistics today. However, logistics is a paradigm that cannot be reduced to the mode of production in a classical meaning. Logistics enables us to understand peculiar forms of racialization, social reproduction, and social difference, along with geopolitical dynamics. In fact, logistics is a specific character of contemporary forms of power, and struggles over logistics and its infrastructures are imperial and tied to conflicts over land and livelihoods in a much broader frame, as well as impossibly entangled, as they are all concerned with the power to define who or what moves, where, when, and how. Therefore, logistics can be framed as a complex and productive multifaceted lens through which a new critical comprehension of actual dynamics needs to be framed and deepened.