bluuebunny/crossref_metadata_2025 huggingface dataset:
Factor structure of the depression anxiety stress Scale-21 (DASS-21): Unidimensionality of the Arabic version among Egyptian drug users
Authors: Ali Amira Mohammed , Green Joseph
Published: September 2019

Background

Emotional distress is common among illicit drug users, and it can negatively affect treatment outcomes and increase the risk of relapse. Nonetheless, instruments that properly measure emotional distress are lacking. Therefore, this study investigated the factor structure of the Arabic Depression Anxiety Stress Scale-21 (DASS-21) in that population.

Methods

The DASS-21 and the Self-stigma of Alcohol Dependence Scale (SSAD) were completed by 149 inpatient Egyptian drug users. The DASS-21 was examined using exploratory factor analysis, partial confirmatory factor analysis, and parallel analysis. For validation testing, correlations between stigma scores and DASS scores were computed.

Results

A one-factor solution provided the best fit to the DASS-21 data. Four items with low loadings were removed. The resulting DASS-17 was also unidimensional, and its reliability was high (0.88). On the validation tests, the DASS scores correlated with the stigma scores as hypothesized.

Conclusion

Subscales of the Arabic version of the DASS-21 do not differentiate between depression and anxiety. A modified 17-item version (the DASS-17) was suitable for measuring overall distress, and the results of convergent validation testing indicated that it was superior to the DASS-21.
Capturing implementation knowledge: applying focused ethnography to study how implementers generate and manage knowledge in the scale-up of obesity prevention programs
Authors: Conte Kathleen P. , Shahid Abeera , Grøn Sisse , Loblay Victoria , Green Amanda , Innes-Hughes Christine , Milat Andrew , Persson Lina , Williams Mandy , Thackway Sarah , Mitchell Jo , Hawe Penelope
Published: September 2019

Background

Bespoke electronic information management systems are being used for large-scale implementation delivery of population health programs. They record sites reached, coordinate activity, and track target achievement. However, many systems have been abandoned or failed to integrate into practice. We investigated the unusual endurance of an electronic information management system that has supported the successful statewide implementation of two evidence-based childhood obesity prevention programs for over 5 years. Upwards of 80% of implementation targets are being achieved.

Methods

We undertook co-designed partnership research with policymakers, practitioners, and IT designers. Our working hypothesis was that the science of getting evidence-based programs into practice rests on an in-depth understanding of the role programs play in the ongoing system of local relationships and multiple accountabilities. We conducted a 12-month multisite ethnography of 14 implementation teams, including their use of an electronic information management system, the Population Health Information Management System (PHIMS).

Results

All teams used PHIMS, but also drew on additional informal tools and technologies to manage, curate, and store critical information for implementation. We identified six functions these tools performed: (1) relationship management, (2) monitoring progress towards target achievement, (3) guiding and troubleshooting PHIMS use, (4) supporting teamwork, (5) evaluation, and (6) recording extra work at sites not related to program implementation. Informal tools enabled practitioners to create locally derived implementation knowledge and provided a conduit between knowledge generation and entry into PHIMS.

Conclusions

Implementation involves knowing and formalizing what to do, as well as how to do it. Our ethnography revealed the importance of hitherto uncharted knowledge about how practitioners develop implementation knowledge about how to do implementation locally, within the context of scaling up. Harnessing this knowledge for local use required adaptive and flexible systems which were enabled by informal tools and technologies. The use of informal tools also complemented and supported PHIMS use suggesting that both informal and standardized systems are required to support coordinated, large-scale implementation. While the content of the supplementary knowledge required to deliver the program was specific to context, functions like managing relationships with sites and helping others in the team may be applicable elsewhere.
A placebo-controlled study comparing the efficacy of intra-articular injections of hyaluronic acid and a novel hyaluronic acid-platelet-rich plasma conjugate in a canine model of osteoarthritis
Authors: Lee Mun-Ik , Kim Jun-Hyung , Kwak Ho-Hyun , Woo Heung-Myong , Han Jeong-Hee , Yayon Avner , Jung Yun-Chan , Cho Jin-Man , Kang Byung-Jae
Published: September 2019

Background

The objective of this study was to assess the efficacy of intra-articular injections of hyaluronic acid (HA) and a novel, on-site conjugate of HA with autologous fibrinogen in platelet-rich plasma (HA-PRP) in a canine model of osteoarthritis (OA)

Methods

Twelve beagle dogs underwent a unilateral resection of the cranial cruciate ligament (CrCL) of the stifle joint. Clinical and radiographic signs of OA were confirmed in all dogs 8 weeks following CrCL resection and prior to treatment. The dogs were randomized into three groups: saline (n= 4), HA (n= 4), and HA-PRP (n= 4). Each dog received intra-articular injections of the respective substance into the affected joint at pre-determined time points. The dogs were assessed for adverse effects for 3 days after each injection and for lameness, pain, range of motion, kinetics, and radiographic OA severity prior to treatment and 3 months after injection. OA severity as determined by radiographic examination was not significantly different among the groups at any time point. The dogs were then humanely euthanatized and the stifle joint assessed by gross and histological examinations.

Results

Dogs treated with four weekly injections of HA or two biweekly injections of HA-PRP were significantly (p< 0.05) better than dogs treated with four weekly injections of saline at 2-, 4-, and 12-week time points based on a comfortable range of motion (CROM) and clinical lameness score. Gait analysis measuring symmetry and weight distribution on pressure sensor walkway showed significantly (p< 0.05) improved limb function for dogs treated with HA and HA-PRP compared with dogs treated with saline yet with better clinical outcome for the HA-PRP-treated group at 12 and 20 weeks follow-up. Gross and histological analysis of synovium and articular cartilage demonstrated significant (p< 0.05) improvement by both treatments groups compared to controls. There was however significantly (p< 0.05) less damage to the cartilage in the HA-PRP group compared to the HA-treated group.

Conclusions

These data suggest that while injection of HA and HA-PRP may be sufficient for short-term amelioration of the symptoms associated with OA, treatment with HA-PRP conjugates may be superior, providing significantly better long-term cartilage preservation.
Would early removal of indwelling catheter effectively prevent urinary retention after hip fracture surgery in elderly patients?
Authors: Kwak Dae-Kyung , Oh Chul-Young , Lim Jeong-Seop , Lee Hyung-Min , Yoo Je-Hyun
Published: September 2019

Background

This study aimed to investigate the incidence and risk factors of postoperative urinary retention (POUR) among elderly patients who underwent hip fracture surgery and to evaluate the effect of indwelling catheterization on the occurrence of POUR.

Materials and methods

From January 2012 to January 2015, consecutive patients aged over 70 years who underwent hip fracture surgery were enrolled in this study. All patients underwent indwelling catheterization due to voiding difficulty upon admission. Demographic data, perioperative variables, and postoperative duration of patient-controlled analgesia and indwelling catheterization, postoperative complications, and mortality were collected. The incidence of POUR was investigated, and the risk factors related to POUR were analyzed using a logistic regression analysis. The cutoff value for the timing of catheter removal was determined using receiver operating characteristic (ROC) curve analysis.

Results

POUR developed in 68 patients (31.8%) of the 214 patients. Of these, 24 (35.3%) were male. The indwelling catheter was left in place for an average of 3.4 days (range, 0–7 days) postoperatively. A significant difference was noted in gender and duration of indwelling catheterization between patients with POUR and without. The cutoff value for the timing of catheter removal as determined by ROC curve analysis was 3.5 postoperative day with 51.4% sensitivity and 71.5% specificity. Multiple logistic regression revealed that the duration of the indwelling catheter [odds ratios (OR), 0.31; p = 0.016)] and male gender (OR, 2.22; p = 0.014) were independent risk factors related to the occurrence of POUR.

Conclusions

The significant risk factors of POUR among elderly patients undergoing hip fracture surgery were early indwelling catheter removal and male gender. Therefore, early removal of indwelling catheter in elderly patients following hip fracture surgery may increase the risk of POUR, especially in male patients.
Combined intrapleural and intrabronchial injection of fibrin glue for closing alveolar pleural fistula: a case report
Authors: Fiorelli Alfonso , Odierna Italia , Scarano Daniele , Caronia Francesco , Failla Andrea , Iannotti Mario , Santini Mario , Pace Caterina
Published: September 2019

Background

The treatment of persistent air leak is a challenge. Herein, we reported the combined intrabronchial and intrapleural injection of fibrin glue using fiber bronchoscopy to seal off an alveolar pleura fistula developed following necrotizing pneumonia in high-risk patient.

Case presentation

A 74-year-old man was intubated in emergency for acute ischemic stroke. Percutaneous dilatational tracheostomy was then performed, and 15 days later patient returned to spontaneous breathing. However, he developed alveolar pleural fistula following necrotizing pneumonia with persistent air leaks. The intrabronchial and intrapleural injection of fibrin glue using fiber bronchoscopy sealed off the alveolar pleura fistula after that other endoscopic treatments as bronchial valve and intrabronchial fibrin glue application had failed.

Conclusions

Our strategy is safe and easy to reproduce. It represents an additional method in the armamentarium of the physicians for the management of PAL when all standard strategies are unfeasible or fail.
Polyglycolic acid sutures embedded in abdominal acupoints for treatment of simple obesity in adults: a randomized control trial
Authors: Chen Li-Shu , Li Yue-Ying , Chen Hao , Liu Bo-Wen , Wang Da-Wei , Zhao Yong-Hua
Published: September 2019

Background

Acupoint catgut embedding therapy characterized by acupoint, needle and catgut are superior to traditional acupuncture, due to exerting more comprehensive therapeutic efficacy. However, it is still deficient in clinical evidence for polyglycolic acid sutures, a novel biodegradable material instead of catgut, embedded for the treatment of simple obesity. In our study, we investigate the efficacy and related mechanism of polyglycolic acid sutures embedded in abdominal acupoints on simple obese persons by a randomized control trial.

Methods

A total of 51 eligible participators were randomly allocated to a polyglycolic acid sutures embedding therapy (PASET) group (n = 28) or control group (n = 23). Participators in PASET group received polyglycolic acid sutures alternatively embedded in abdominal I group and II group acupoints in odd and even number therapeutic courses, and participators in control group were required to perform lifestyle modification. The duration of the study was 10 weeks.

Results

It suggested that PASET significantly reduced weight, body mass index, hip circumference, waist circumference, waist/hip ratio, waist-to-height ratio and thickness of abdominal subcutaneous fat tissue compared with those before treatment (p < 0.01), but lifestyle modification only illustrated downward trend of weight (p < 0.05). Moreover, PASET group also improved the evaluated scores in aspects of physical function, self-esteem, public distress and sexual life, as well as decreased blood pressure, glycemia, low density lipoprotein, uric acid and the levels of tumor necrosis factor-alpha, interleukin-1β, and increased high density lipoprotein in comparison with those before treatment (p < 0.05), whose efficacies are superior to control group. Additionally, our results also indicate PASET is relative safe and its pain and discomfort can be tolerable.

Conclusions

PASET distinctly ameliorates anthropometric data and quality of life in obese population, which associates with improvements of metabolic profile and inflammatory response. Based on the advantageous actions, we think PASET is an effective therapeutic approach to simple obesity treatment.

Trial registration ChiCTR, ChiCTR1800015591. Registered 10 April 2018, http://www.chictr.org.cn/showproj.aspx?proj=23258
Ocular manifestations in Gorlin-Goltz syndrome
Authors: Moramarco Antonietta , Himmelblau Ehud , Miraglia Emanuele , Mallone Fabiana , Roberti Vincenzo , Franzone Federica , Iacovino Chiara , Giustini Sandra , Lambiase Alessandro
Published: September 2019

Background

Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare genetic disorder that is transmitted in an autosomal dominant manner with complete penetrance and variable expressivity. It is caused in 85% of the cases with a known etiology by pathogenic variants in the PTCH1 gene, and is characterized by a wide range of developmental abnormalities and a predisposition to multiple neoplasms. The manifestations are multiple and systemic and consist of basal cell carcinomas in various regions, odontogenic keratocistic tumors and skeletal anomalies, to name the most frequent. Despite the scarce medical literature on the topic, ocular involvement in this syndrome is frequent and at the level of various ocular structures. Our study focuses on the visual apparatus and its annexes in subjects with this syndrome, in order to better understand how this syndrome affects the ocular system, and to evaluate with greater accuracy and precision the nature of these manifestations in this group of patients.

Results

Our study confirms the presence of the commonly cited ocular findings in the general literature regarding the syndrome [hypertelorism (45.5%), congenital cataract (18%), nystagmus (9%), colobomas (9%)] and highlights strabismus (63% of the patients), epiretinal membranes (36%) and myelinated optic nerve fiber layers (36%) as the most frequent ophthalmological findings in this group of patients.

Conclusions

The presence of characteristic and frequent ocular signs in the Gorlin- Goltz syndrome could help with the diagnostic process in subjects suspected of having the syndrome who do not yet have a diagnosis. The ophthalmologist has a role as part of a multidisciplinary team in managing these patients. The ophthalmological follow-up that these patients require, can allow, if necessary, a timely therapy that could improve the visual prognosis of such patients.
Individualized treatment with denosumab in children with osteogenesis imperfecta – follow up of a trial cohort
Authors: Hoyer-Kuhn Heike , Rehberg Mirko , Netzer Christian , Schoenau Eckhard , Semler Oliver
Published: September 2019

Background

Osteogenesis imperfecta (OI) is a rare disease leading to hereditary bone fragility. Nearly 90% of cases are caused by mutations in the collagen genes COL1A1/A2 (classical OI) leading to multiple fractures, scoliosis, short stature and nonskeletal findings as blue sclera, hypermobility of joints, bone pain and delayed motor function development. Bisphosphonates are used in most moderate and severely affected patients assuming that an increase of bone mineral density might reduce fractures and bone pain in patients with OI. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. First data from small clinical trials promised a high efficacy of Denosumab in children with OI. Aim of this analysis was a retrospective evaluation of an individualized biomarker-associated treatment regime with Denosumab in 10 children with classical OI which were followed for 1 year after their participation in a pilot trial with Denosumab. Therefore urinary deoxypyridinoline levels were evaluated frequently as an osteoclastic activity marker and depending on that levels Denosumab injections were scheduled individually.

Methods

Ten patients (age range: 6.16–12.13 years; all participated in the former OI-AK phase 2 trial (NCT01799798)) were included in the follow-up period. Denosumab was administered subcutaneously depending on the individual urinary excretion course of deoxypyridinoline (DPD/Crea) as osteoclastic activity marker with 1 mg/kg body weight. DPD/Crea levels were evaluated before denosumab administration and afterwards. If patients present after an initial decrease after injection with a re-increase up to the DPD/crea level before Denosumab injection next dosage was planned. Changes of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 12 month was evaluated. Safety was assessed by bone metabolism markers and side effect reporting.

Results

During follow-up mean relative change of lumbar aBMD was − 6.4%. Lumbar spine aBMD z-Scores decreased from − 1.01 ± 2.61 (mean ± SD) to − 1.91 ± 2.12 (p = 0.015). Mobility changed not significantly (GMFM-88 -6.49 ± 8.85% (p = 0.08). No severe side effects occurred. Dose intervals could be extended in the mean from 12 weeks previously to 20.3 weeks.

Conclusions

On average, it was possible to prolong the intervals between drug administrations and to reduce the total dose about by 25% without a decrease of mobility or change of vertebral shape despite a reduction of lumbar aBMD during 1 year of biomarker-directed Denosumab treatment. Further trials are necessary to balance side effects and highest efficacy in children.
Estimating the fiscal impact of rare diseases using a public economic framework: a case study applied to hereditary transthyretin-mediated (hATTR) amyloidosis
Authors: Connolly Mark P. , Panda Saswat , Patris Julien , Hazenberg Bouke P. C.
Published: September 2019

Background

A wide range of rare diseases can have fiscal impacts on government finances that extend beyond expected healthcare costs. Conditions preventing people from achieving national lifetime work averages will influence lifetime taxes paid and increase the likelihood of dependence on public income support. Consequently, interventions that influence projected lifetime work activity, morbidity and mortality can have positive and negative fiscal consequences for government. The aim of this study was to apply a public economic framework to a rare disease that takes into consideration a broad range of costs that are relevant to government in relation to transfers received and taxes paid. As a case study we constructed a simulation model to calculate the fiscal life course of an individual with hereditary transthyretin-mediated (hATTR) amyloidosis in The Netherlands. In this lethal disease different progressive disease scenarios occur, including polyneuropathy and/or cardiomyopathy.

Results

Due to progressive disability, health care resource use, and early death, hATTR amyloidosis with polyneuropathy receives more transfers from government compared to the general population. In a scenario where a patient is diagnoses with hATTR at age 45, an individual pays €180,812 less in lifetime taxes and receives incrementally €111,695 in transfers from the government, compared to a person without hATTR. Patients suffering from cardiomyopathy die after median 4 years. The health costs of this scenario are therefore lower than that of the other polyneuropathy-based scenarios.

Conclusions

The fiscal analysis illustrates how health conditions influence not only health costs, but also the cross-sectorial public economic burden attributed to lost tax revenues and public disability allowances. Due to the progressive nature of hATTR amyloidosis used in this study, public costs including disability increase as the disease progresses with reduced lifetime taxes paid. The results indicate that halting disease progression early in the disease course would generate fiscal benefits beyond health benefits for patients. This analysis highlights the fiscal consequences of diseases and the need for broader perspectives applied to evaluate health conditions. Conventional cost-effectiveness framework used by many health technology assessment agencies have well-documented limitations in the field of rare diseases and fiscal modeling should be a complementary approach to consider.
C-banding and AgNOR-staining were still effective complementary methods to indentify chromosomal heteromorphisms and some structural abnormalities in prenatal diagnosis
Authors: Zhu Jian Jiang , Qi Hong , Cai Li Rong , Wen Xiao Hui , Zeng Wen , Tang Guo Dong , Luo Yao , Meng Ran , Mao Xue Qun , Zhang Shao Qin
Published: September 2019

Background

In prenatal diagnosis, CMA has begun to emerge as a favorable alternative to karyotype analysis, but it could not identify balanced translocations, triploidies, inversion and heteromorphisms. Therefore, conventional cytogenetic and specific staining methods still play an important role in the work-up of chromosome anomaly. This study investigated the application of C-banding and AgNOR-staining techniques in prenatal diagnosis of chromosomal heteromorphisms and some structure abnormalities.

Results

Among the 2970 samples, the incidence of chromosomal heteromorphisms was 8.79% (261/2970). The most frequent was found to be chromosome Y (2.93%, 87/2970), followed by chromosome 1 (1.65 %, 49/2970), 9 (1.52 %, 45/2970), 22 (0.77 %, 23/2970) and 15 (0.64 %, 19/2970). We compared the incidence of chromosomal heteromorphisms between recurrent spontaneous abortion (RSA) group and control group. The frequency of autosomal hetermorphisms in RSA group was 7.63% higher than that in control group (5.78%), while the frequency of Y chromosomal heteromorphisms was 4.76% lower than that in control group (5.71%). Here we summarized 4 representative cases, inv (1) (p12q24), psu dic (4;17) (p16.3;p13.3), r(X)(p11; q21) and an isodicentric bisatellited chromosome to illustrate the application of C-banding or AgNOR-staining, CMA or NGS was performed to detect CNVs if necessary.

Conclusions

This study indicated that C-banding and AgNOR-staining were still effective complementary methods to identify chromosomal heteromorphisms and marker chromosomes or some structural rearrangements involving the centromere or acrocentric chromosomes. Our results suggested that there was no evidence for an association between chromosomal heteromorphisms and infertility or recurrent spontaneous abortions. Undoubtedly, sometimes we needed to combine the results of CMA or CNV-seq to comprehensively reflect the structure and aberration of chromosome segments. Thus, accurate karyotype reports and genetic counseling could be provided.
Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy
Authors: Xia Mao , Luo Dongjun , Dong Jie , Zheng Meihong , Meng Gang , Wu Junhua , Wei Jiwu
Published: September 2019

Background

Replication-competent oncolytic viruses (OVs) have been proven to be a potent anticancer weapon for clinical therapy. The preexisting neutralizing antibody in patients is a big challenge for oncolytic efficacy of OVs. Graphene oxide sheets (GOS) possess excellent biological compatibility and are easy to decorate for targeted delivery.

Methods

We generated PEI-GOS-PEG-FA (Polyethyleneimine-Graphene oxide sheets-Polyethylene glycol-Folic acid). After intravenous injection, the distribution of PEI-GOS-PEG-FA in tumor-bearing mice was visualized by the IVIS Lumina XR system. Then, the oncolytic measles virus (MV-Edm) was coated with PEI-GOS-PEG-FA to form a viral-GOS complex (GOS/MV-Edm). The oncolytic effects of GOS/MV-Edm were investigated both in vitro and in vivo.

Results

GOS/MV-Edm exhibited higher infectivity and enhanced oncolysis. In tumor-bearing mice, GOS/MV-Edm had significantly elevated viral replication within the tumor mass, and achieved an improved antitumor effect. Then, we confirmed that GOS/MV-Edm entered cancer cells via the folate receptor instead of CD46, a natural cognate receptor of MV-Edm. GOS/MV-Edm remained the infectivity in murine cells that lack CD46. Finally, we found that GOS/MV-Edm was effectively protected from neutralization in the presence of antiserum both in vitro and in vivo. In passively antiserum immunized tumor-bearing mice, the survival was remarkably improved with intravenous injection of GOS/MV-Edm.

Conclusion

Our findings demonstrate that GOS/MV-Edm displays significantly elevated viral replication within the tumor mass, leading to an improved antitumor effect in solid tumor mouse model. Our study provided a novel strategy to arm OVs for more efficient cancer therapy. That may become a promising therapeutic strategy for cancer patients.
UFM1 suppresses invasive activities of gastric cancer cells by attenuating the expression of PDK1 through PI3K/AKT signaling
Authors: Lin Jian-Xian , Xie Xin-Sheng , Weng Xiong-Feng , Qiu Sheng-Liang , Yoon Changhwan , Lian Ning-Zi , Xie Jian-Wei , Wang Jia-Bin , Lu Jun , Chen Qi-Yue , Cao Long-Long , Lin Mi , Tu Ru-Hong , Yang Ying-Hong , Huang Chang-Ming , Zheng Chao-Hui , Li Ping
Published: September 2019

Background

UFM1 has been found to be involved in the regulation of tumor development. This study aims to clarify the role and potential molecular mechanisms of UFM1 in the invasion and metastasis of gastric cancer.

Methods

Expression of UFM1 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was analyzed by Western blotting, immunohistochemistry, and realtime PCR. Its correlation with the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. The effects of UFM1 on the invasion and migration of gastric cancer cells were determined by the wound and trans-well assays, and the effect of UFM1 on subcutaneous tumor formation was verified in nude mice. The potential downstream targets of UFM1 and related molecular mechanisms were clarified by the human protein kinase assay and co-immunoprecipitation technique.

Results

Compared with the corresponding adjacent tissues, the transcription level and protein expression level of UFM1 in gastric cancer tissues were significantly downregulated (P < 0.05). The 5-year survival rate of gastric cancer patients with low UFM1 expression was significantly lower than the patients with high UFM1 expression (42.1% vs 63.0%, P < 0.05). The invasion and migration abilities of gastric cancer cells with stable UFM1 overexpression were significantly decreased, and the gastric cancer cells with UFM1 stable knockdown showed the opposite results; similar results were also obtained in the nude mouse model. Further studies have revealed that UFM1 could increase the ubiquitination level of PDK1 and decrease the expression of PDK1 at protein level, thereby inhibiting the phosphorylation level of AKT at Ser473. Additionally, the effect of UFM1 on gastric cancer cell function is dependent on the expression of PDK1. The expression level of UFM1 can improve the poor prognosis of PDK1 in patients with gastric cancer.

Conclusion

UFM1 suppresses the invasion and metastasis of gastric cancer by increasing the ubiquitination of PDK1 through negatively regulating PI3K/AKT signaling.
The management of unanticipated difficult airways in children of all age groups in anaesthetic practice - the position paper of an expert panel
Authors: Walas Wojciech , Aleksandrowicz Dawid , Kornacka Maria , Gaszyński Tomasz , Helwich Ewa , Migdał Marek , Piotrowski Andrzej , Siejka Grażyna , Szczapa Tomasz , Bartkowska-Śniatkowska Alicja , Halaba Zenon P.
Published: September 2019

Children form a specific group of patients, as there are significant differences between children and adults in both anatomy and physiology. Difficult airway may be unanticipated or anticipated. Difficulties encountered during intubation may cause hypoxia, hypoxic brain injury and, in extreme situations, may result in the patient’s death. There are few paediatric difficult-airway guidelines available in the current literature, and some of these have significant limitations. This position paper, intended for unanticipated difficult airway, was elaborated by the panel of specialists representing the Polish Society of Anaesthesiology and Intensive Care as well as the Polish Neonatal Society. It covers both elective intubation and emergency situations in children in all age groups. An integral part of the paper is an algorithm. The paper describes in detail all stages of the algorithm considering some modification in specific age groups, i.e. neonates.
Familial Mediterranean Fever: an unusual cause of liver disease
Authors: Maggio Maria Cristina , Castiglia Maria , Corsello Giovanni
Published: September 2019

Background

Familial Mediterranean Fever is an autoinflammatory disease typically expressed with recurrent attacks of fever, serositis, aphthous stomatitis, rash. Only a few reports describe the association with hepatic involvement.

Case presentation

We describe the clinical case of a child affected, since the age of 1 year, by recurrent fever, aphthous stomatitis, rash, arthralgia, associated with abdominal pain, vomiting, lymphadenopathy. The diagnosis of Familial Mediterranean Fever was confirmed by the genetic study of MEFV gene; the homozygous mutation M694 V in exon was documented. A partial control of attacks was obtained with colchicine. The child continued to manifest only recurrent episodes of abdominal pain without fever, however serum amyloid A persisted high, in association with enhanced levels of CRP, AST and ALT (1.5 x n.v.). The dosage of colchicine was increased step by step and the patient achieved a better control of symptoms and biochemical parameters. However, the patient frequently needed an increase in the dose of colchicine, suggesting the possible usefulness of anti-interleukin-1 beta treatment.

Conclusions

The unusual presentation of Familial Mediterranean Fever with liver disease suggests the role of inflammasome in hepatic inflammation. Colchicine controls systemic inflammation in most of the patients; however, subclinical inflammation can persist in some of them and can manifest with increased levels of CRP, ESR, serum amyloid A also in attack-free intervals.
Li-Fraumeni syndrome: not a straightforward diagnosis anymore—the interpretation of pathogenic variants of low allele frequency and the differences between germline PVs, mosaicism, and clonal hematopoiesis
Authors: Batalini Felipe , Peacock Ellie G. , Stobie Lindsey , Robertson Alison , Garber Judy , Weitzel Jeffrey N. , Tung Nadine M.
Published: September 2019

The introduction of next-generation sequencing has resulted in testing multiple genes simultaneously to identify inherited pathogenic variants (PVs) in cancer susceptibility genes. PVs with low minor allele frequencies (MAFs) (< 25–35%) are highlighted on germline genetic test reports. In this review, we focus on the challenges of interpreting PVs with low MAF in breast cancer patients undergoing germline testing and the implications for management.

The clinical implications of a germline PV are substantial. For PV carriers in high-penetrance genes like BRCA1, BRCA2, and TP53, prophylactic mastectomy is often recommended and radiation therapy avoided when possible for those with Li-Fraumeni syndrome (LFS). For germline PV carriers in more moderate-risk genes such as PALB2, ATM, and CHEK2, annual breast MRI is recommended and prophylactic mastectomies considered for those with significant family histories. Detection of PVs in cancer susceptibility genes can also lead to recommendations for other prophylactic surgeries (e.g., salpingo-oophorectomy) and increased surveillance for other cancers. Therefore, recognizing when a PV is somatic rather than germline and distinguishing somatic mosaicism from clonal hematopoiesis (CH) is essential. Mutational events that occur at a post-zygotic stage are somatic and will only be present in tissues derived from the mutated cell, characterizing classic mosaicism. Clonal hematopoiesis is a form of mosaicism restricted to the hematopoietic compartment.

Among the genes in multi-gene panels used for germline testing of breast cancer patients, the detection of a PV with low MAF occurs most often in TP53, though has been reported in other breast cancer susceptibility genes. Distinguishing a germline TP53 PV (LFS) from a somatic PV (TP53 mosaicism or CH) has enormous implications for breast cancer patients and their relatives.

We review how to evaluate a PV with low MAF. The identification of the PV in another tissue confirms mosaicism. Older age, exposure to chemotherapy, radiation, and tobacco are known risk factors for CH, as is the absence of a LFS-related cancer in the setting of a TP53 PV with low MAF. The ability to recognize and understand the implications of somatic PVs, including somatic mosaicism and CH, enables optimal personalized care of breast cancer patients.
Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial
Authors: Adamo Barbara , Bellet Meritxell , Paré Laia , Pascual Tomás , Vidal Maria , Pérez Fidalgo José A. , Blanch Salvador , Martinez Noelia , Murillo Laura , Gómez-Pardo Patricia , López-González Ana , Amillano Kepa , Canes Jordi , Galván Patricia , González-Farré Blanca , González Xavier , Villagrasa Patricia , Ciruelos Eva , Prat Aleix
Published: September 2019

Background

The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed.

Methods

Postmenopausal women with untreated stage I–III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures.

Results

Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1–2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (− 73.2%) was superior to both monotherapy arms combined (− 49.9%;p = 0.001) and mVNB (− 19.1%;p < 0.001). The anti-proliferative effect of LTZ+mVNB (− 73.2%) was numerically higher compared to LTZ (− 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysisp = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases.

Conclusions

Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted.

Trial registration

NCT02802748, registered 16 June 2016.
The impact of surgeon and patient treatment preferences in an orthopaedic trauma surgery trial
Authors: Keding Ada , Handoll Helen , Brealey Stephen , Jefferson Laura , Hewitt Catherine , Corbacho Belen , Torgerson David , Rangan Amar
Published: September 2019

Background

Surgeon and patient treatment preferences are important threats to the internal and external validity of surgical trials such as PROFHER, which compared surgical versus non-surgical treatment for displaced fractures of the proximal humerus in adults. We explored the treatment preferences expressed by surgeons and patients in the trial and how these impacted on patient selection, trial conduct and patient outcome.

Methods

A series of exploratory secondary analyses of the PROFHER trial data were undertaken. We reviewed the extent of surgeon and patient treatment preferences (surgery or not surgery) at screening (n = 1250) as well as prior preference (including no preference) of randomised patients (n = 250), and assessed their impact on recruitment and adherence to follow-up and rehabilitation. Changes in treatment after 2 years’ follow-up were explored. Patient preference and characteristics associated with trial inclusion or treatment preference (t test, chi-squared test, Wilcoxon rank-sum test) were included as treatment interaction terms in the primary trial analysis of shoulder functioning (Oxford Shoulder Score, OSS).

Results

Surgeons excluded 17% of otherwise eligible patients based on lack of equipoise; these patients had less complex fractures (p < 0.001) and tended to be older (p = 0.062). Surgeons were more likely to recommend surgery for patients under 65 years of age (p = 0.059) and who had injured their right shoulder (p = 0.052). Over half of eligible patients (56%) did not consent to take part in the trial; these patients tended to be older (p = 0.022), with a preference for not surgery (74%; which was associated with older age, p = 0.039). There were no differential treatment effects (p value of interaction) for shoulder functioning (OSS) based on subgroups of patient preference (p = 0.751), age group (p = 0.264), fracture type (p = 0.954) and shoulder dominance (p = 0.850). Patients who were randomised to their preferred treatment had better follow-up rates (94 vs 84% at 2 years) and treatment adherence (90 vs 83% reported completing home exercises). Patients who were not randomised to their preferred treatment were more likely to change their treatment preference at 24 months (60 vs 26%).

Conclusions

The robustness of the PROFHER trial findings was confirmed against possible bias introduced by surgeon and patient preferences. The importance of collecting preference data is highlighted.

Trial registration

ISRCTN50850043. Registered on 25 March 2008.
Collaborative care model for treatment of persistent symptoms after concussion among youth (CARE4PCS-II): Study protocol for a randomized, controlled trial
Authors: McCarty Carolyn A. , Zatzick Douglas , Hoopes Teah , Payne Katelyn , Parrish Rebecca , Rivara Frederick P.
Published: September 2019

Background

Currently, there is limited evidence to guide intervention and service delivery coordination for youth who suffer a concussion and subsequently experience persistent post-concussive symptoms (PCS) (Lumba-Brown et al. JAMA Pediatr 172(11):e182853, 2018; Lumba-Brown A et al. JAMA Pediatr 172(11):e182847, 2018). We have developed a collaborative care intervention with embedded cognitive-behavioral therapy, care management, and stepped-up psychotropic medication consultation to address persistent PCS and related psychological comorbidities. The CARE4PCS-II study was designed to assess whether adolescents with persistent symptoms after sports-related concussion will demonstrate better outcomes when receiving this collaborative care intervention compared to a usual care (control) condition.

Methods/design

This investigation is a randomized comparative effectiveness trial to receive intervention (collaborative care) or control (usual care). Two hundred sports-injured male and female adolescents aged 11–18 years with three or more post-concussive symptoms that persist for at least 1 month but less than 9 months after injury will be recruited and randomized into the study. The trial focuses on the effects of the intervention on post-concussive, depressive, and anxiety symptoms measured 3, 6, and 12 months after baseline.

Discussion

The CARE4PCS II study is a large comparative effectiveness trial targeting symptomatic improvements in sports injured adolescents after concussion. The study is unique in its adaptation of the collaborative care model to a broad spectrum of primary care, sports medicine, and school settings. The investigation incorporates novel elements such as the delivery of CBT through HIPAA complaint video conferenceing technology and has excellent widespread dissemination potential should effectiveness be demonstrated.

Trial registration

ClinicalTrials.gov, NCT03034720. Registered on January 27, 2017.
Characterising residual malaria transmission in forested areas with low coverage of core vector control in central Viet Nam
Authors: Edwards Hannah Margaret , Chinh Vu Duc , Le Duy Bui , Thanh Pham Vinh , Thang Ngo Duc , Trang Dao Minh , Chavez Irwin , Hii Jeffrey
Published: September 2019

Background

Despite great success in significantly reducing the malaria burden in Viet Nam over recent years, the ongoing presence of malaria vectors and Plasmodium infection in remote forest areas and among marginalised groups presents a challenge to reaching elimination and a threat to re-emergence of transmission. Often transmission persists in a population despite high reported coverage of long-lasting insecticidal nets (LLINs), the mainstay control method for malaria. To investigate what factors may contribute to this, a mixed-methods study was conducted in Son Thai commune, a community in south-central Viet Nam that has ongoing malaria cases despite universal LLIN coverage. A cross-sectional behavioural and net-coverage survey was conducted along with observations of net use and entomological collections in the village, farm huts and forest sites used by members of the community.

Results

Most community members owned a farm hut plot and 71.9% of adults aged 18+ years sometimes slept overnight in the farm hut, while one-third slept overnight in the forest. Ownership and use of nets in the village households was high but in the farm huts and forest was much lower; only 44.4% reported regularly using a bednet in the farm and 12.1% in the forest. No primary anopheline species were captured in the village, but Anopheles dirus (s.l.) (n = 271) and An. maculatus (s.l.) (n = 14) were captured as far as 4.5 km away in farm huts and forest. A high proportion of biting was conducted in the early evening before people were under nets. Entomological inoculation rates (EIR) of An. dirus (s.l.) were 17.8 and 25.3 infectious bites per person per year in the outdoor farm hut sites and forest, respectively, for Plasmodium falciparum and 25.3 in the forest sites for P. vivax.

Conclusions

Despite high net coverage in the village, gaps in coverage and access appear in the farm huts and forest where risk of anopheline biting and parasite transmission is much greater. Since subsistence farming and forest activities are integral to these communities, new personal protection methods need to be explored for use in these areas that can ideally engage with the community, be durable, portable and require minimal behavioural change.
Associations between objectively assessed and questionnaire-based sedentary behaviour with body mass index and systolic blood pressure in Kuwaiti adolescents
Authors: Hashem Rawan , Rey-Lόpez Juan Pablo , Hamer Mark , McMunn Anne , Rowlands Alex , Whincup Peter H. , Owen Christopher G. , Ding Ding , Powell Lauren , Stamatakis Emmanuel
Published: September 2019

Objective

Kuwait has one of the highest obesity rates in the world. This study examined the associations between sedentary behaviour (objectively measured and self-reported), adiposity and systolic blood pressure in a sample of adolescents residing in Kuwait. Data was obtained from the Study of Health and Activity among adolescents in Kuwait (2012–2013). The sample included a total of 435 adolescents (201 boys). Outcomes were age- and sex specific body mass index Z-scores and systolic blood pressure. Exposures were total sedentary behaviour measured by accelerometry and time spent in some sedentary behaviours (television viewing, video games, computer use and total screen-time). We used multiple linear regression analyses, adjusted for age, governorate, maternal education and physical activity, to examine associations between sedentary behaviour and adiposity and systolic blood pressure.

Results

Only 2 statistically significant associations were found between sedentary behaviour and the study outcomes: body mass in boys was directly associated with higher sedentary time [β (95% CIs) 0.003 (0.00 to 0.06)]; body mass index was inversely associated with videogames in both sexes [girls: β (95% CIs) − 0.17 (− 0.48 to − 0.04); boys: − 0.24 (− 0.57 to − 0.12)]. In this sample of Kuwaiti adolescents, sedentary behaviour showed limited deleterious associations with adiposity and systolic blood pressure.
Resistance training-induced gains in knee extensor strength are related to increased neural cell adhesion molecule expression in older adults with knee osteoarthritis
Authors: Voigt Thomas B. , Tourville Timothy W. , Falcone Michael J. , Slauterbeck James R. , Beynnon Bruce D. , Toth Michael J.
Published: September 2019

Objective

Resistance training (RT) can improve whole muscle strength without increasing muscle fiber size or contractility. Neural adaptations, which lead to greater neural activation of muscle, may mediate some of these improvements, particularly in older adults, where motor neuron denervation is common. The purpose of this study was to explore the relationship of neural adaptations, as reflected by neural cell adhesion molecule (NCAM) expression, to improvements in (1) whole muscle strength and (2) muscle fiber size following RT in older adults with knee osteoarthritis. We performed whole muscle strength measurements and immunohistochemical analysis of fiber size, type, and NCAM expression before and after a 14-week RT program.

Results

RT increased whole-muscle strength as measured by 1-repetition maximum (1-RM) leg press (P = 0.01), leg extension (P = 0.03), and knee extensor peak torque (P = 0.050), but did not alter NCAM expression. Greater NCAM expression in myosin heavy chain (MHC) II fibers was associated with greater whole muscle strength gains (knee extensor peak torque r = 0.93; P < 0.01) and greater MHC II fiber size (r = 0.79; P < 0.01). Our results suggest that training-induced NCAM expression, and neural adaptations more generally, may be important for RT-induced morphological and functional improvements in older adults.

Trial registration NCT01190046