bluuebunny/crossref_metadata_2025 huggingface dataset:
Initiation of droxidopa during hospital admission for management of refractory neurogenic orthostatic hypotension in severely ill patients
Authors: McDonell Katherine E. , Preheim Brock A. , Diedrich Andre’ , Muldowney James A. S. , Peltier Amanda C. , Robertson David , Biaggioni Italo , Shibao Cyndya A.
Published: August 2019

Orthostatic hypotension (OH) is a common cause of hospitalization, particularly in the elderly. Hospitalized patients with OH are often severely ill, with complex medical comorbidities and high rates of disability. Droxidopa is a norepinephrine precursor approved for the treatment of neurogenic OH (nOH) associated with autonomic failure that is commonly used in the outpatient setting, but there are currently no data regarding the safety and efficacy of droxidopa initiation in medically complex patients. We performed a retrospective review of patients started on droxidopa for refractory nOH while hospitalized at Vanderbilt University Medical Center between October 2014 and May 2017. Primary outcome measures were safety, change in physician global impression of illness severity from admission to discharge, and persistence on medication after 180‐day follow‐up. A total of 20 patients were identified through chart review. Patients were medically complex with high rates of cardiovascular comorbidities and a diverse array of underlying autonomic diagnoses. Rapid titration of droxidopa was safe and well tolerated in this cohort, with no cardiovascular events or new onset arrhythmias. Supine hypertension requiring treatment occurred in four patients. One death occurred during hospital admission due to organ failure associated with end‐stage amyloidosis. Treating physicians noted improvements in presyncopal symptoms in 80% of patients. After 6 months, 13 patients (65%) continued on droxidopa therapy. In a retrospective cohort of hospitalized, severely ill patients with refractory nOH, supervised rapid titration of droxidopa was safe and effective. Treatment persistence was high, suggesting that symptomatic benefit extended beyond acute intervention.
Visceral fat, cardiometabolic risk factors, and nocturnal blood pressure fall in young adults with primary hypertension
Authors: Miazgowski Tomasz , Taszarek Aleksandra , Miazgowski Bartosz
Published: August 2019

The aims of this study were to assess associations of body fat levels and distribution with metabolic profiles and 24‐hour blood pressure in young adults with primary hypertension. Visceral fat (VF) was estimated using dual‐energy X‐ray absorptiometry. VF was highly significantly associated with a high frequency of overweight/obesity, impaired fasting glucose, increased levels of triglycerides and LDL‐cholesterol, and lowered level of HDL‐cholesterol. The value of systolic blood pressure (SBP) nocturnal fall was similar between patients receiving RAAS inhibitors, beta‐blockers, and calcium channel blockers. In multiple regression, the VF/weight ratio after adjusting for age, gender, total fat, and chronotherapeutic drug delivery was associated with the percentage SBP nocturnal fall (β = −.3108; 95% CI: −0.5923; −0.0980; P = .013). In males, excess VF increased the odds by 2.3 times for non‐dipping blood pressure. Our results suggest that in young adult hypertensives, the VF/weight ratio might be associated with non‐dipping blood pressure.
Cathepsin B increases ENaC activity leading to hypertension early in nephrotic syndrome
Authors: Larionov Alexey , Dahlke Eileen , Kunke Madlen , Zanon Rodriguez Luis , Schiessl Ina M. , Magnin Jean‐Luc , Kern Ursula , Alli Abdel A. , Mollet Geraldine , Schilling Oliver , Castrop Hayo , Theilig Franziska
Published: August 2019

The NPHS2 gene, encoding the slit diaphragm protein podocin, accounts for genetic and sporadic forms of nephrotic syndrome (NS). Patients with NS often present symptoms of volume retention, such as oedema formation or hypertension. The primary dysregulation in sodium handling involves an inappropriate activation of the epithelial sodium channel, ENaC. Plasma proteases in a proteinuria‐dependent fashion have been made responsible; however, referring to the timeline of symptoms occurring and underlying mechanisms, contradictory results have been published. Characterizing the mouse model of podocyte inactivation of NPHS2 (Nphs2∆pod) with respect to volume handling and proteinuria revealed that sodium retention, hypertension and gross proteinuria appeared sequentially in a chronological order. Detailed analysis of Nphs2∆pod during early sodium retention, revealed increased expression of full‐length ENaC subunits and αENaC cleavage product with concomitant increase in ENaC activity as tested by amiloride application, and augmented collecting duct Na+/K+‐ATPase expression. Urinary proteolytic activity was increased and several proteases were identified by mass spectrometry including cathepsin B, which was found to process αENaC. Renal expression levels of precursor and active cathepsin B were increased and could be localized to glomeruli and intercalated cells. Inhibition of cathepsin B prevented hypertension. With the appearance of gross proteinuria, plasmin occurs in the urine and additional cleavage of γENaC is encountered. In conclusion, characterizing the volume handling of Nphs2∆pod revealed early sodium retention occurring independent to aberrantly filtered plasma proteases. As an underlying mechanism cathepsin B induced αENaC processing leading to augmented channel activity and hypertension was identified.
Hepatic pedicle endometriosis: Case report and review of the literature
Authors: Eychenne Camille , Suc Bertrand , Delchier Marie C. , Vidal Fabien , Rimailho Jacques , Illac Claire , Breibach Florence , Vaysse Charlotte , Chantalat Elodie
Published: August 2019

The localization of endometriotic disease in the hepatic pedicle has never been reported to date. We report the first case of a 67‐year‐old postmenopausal patient having presented an endometriotic lesion in the hepatic pedicle. A surgical biopsy was needed to confirm the diagnosis after a first radiologic biopsy that concluded the presence of a mucinous cystic tumor with low‐grade dysplasia. Medical treatment with aromatase inhibitors was carried out because of the inextirpable nature of the lesion. The diagnosis and therapeutic management of this rarely occurring lesion of atypical localization in a postmenopausal patient is presented here. A review of the literature on this localization could have led to a damaging surgical treatment due to the different diagnoses suggested. Management of endometriosis relies on a multidisciplinary approach that each practitioner must know how to broach with patients of all ages.
Impact of inhaled nitric oxide stewardship programme in a neonatal intensive care unit
Authors: Ahearn Joshua , Panda Malavika , Carlisle Hazel , Chaudhari Tejasvi
Published: August 2019

Aim

Inhaled nitric oxide (iNO) is the most common, although expensive, therapy for persistent pulmonary hypertension of the newborn and hypoxaemic respiratory failure. With significant variation in iNO delivery practices amongst clinicians, this study aimed to assess the effectiveness of a stewardship programme in increasing clinician compliance with revised, standardised protocols and to measure the impact of compliance on iNO therapy use.

Methods

Initiation and weaning protocols for iNO were introduced to the neonatal intensive care unit at The Centenary Hospital on 01 March 2016. A 2‐year stewardship programme was utilised to assess protocol compliance and the resulting iNO usage impacts were measured. A combined retrospective and prospective study from 1 March 2014 to 28 February 2018 was conducted to compare the patterns of iNO utilisation between the pre‐ and post‐stewardship cohorts.

Results

The pre‐stewardship cohort incorporated 18 neonates, receiving 19 iNO treatment episodes, and 18 neonates, receiving 21 iNO treatment episodes, in the post‐stewardship cohort. No significant difference in patient demographics was determined. Compliance with the protocols improved from 61% in year 1 to 88% in year 2 of the stewardship programme. Significant reductions were observed in median total hours of iNO therapy per patient (P = 0.0014) and in median time from therapy initiation to initial wean (P < 0.0001). The cost of iNO therapy reduced 52% during the stewardship programme with no increase in adverse patient outcomes.

Conclusion

An iNO stewardship programme could be safely implemented in any NICU leading to increased protocol compliance with a beneficial reduction in iNO usage and cost.
Melatonin protects mouse oocytes from DNA damage by enhancing nonhomologous end‐joining repair
Authors: Leem Jiyeon , Bai Guang‐Yu , Kim Jae‐Sung , Oh Jeong Su
Published: August 2019

Mammalian oocytes remain arrested at the first prophase of meiosis in ovarian follicles for an extended period. During this protracted arrest, oocytes are remarkably susceptible to the accumulation of DNA damage. Melatonin (N‐acetyl‐5‐methoxytryptamine), a hormone secreted by the pineal gland, has diverse effects on various physiological processes. However, the effect of melatonin on DNA damage response in mammalian oocytes has not been explored. Here, we showed that melatonin protected mouse oocytes from DNA damage induced by double‐strand breaks (DSBs) during prophase arrest and subsequently improved oocyte quality. We found that DNA damage during prophase arrest impaired subsequent meiotic maturation and deteriorated oocyte quality, increasing chromosome fragmentation, spindle abnormality, mitochondrial aggregation, and oxidative stress. However, melatonin treatment during DNA damage accumulation at prophase improved meiotic maturation and relieved the quality decline of oocytes. In addition, melatonin inhibited the accumulation of DNA damage during prophase arrest by reducing the γ‐H2AX levels. Although activated ATM levels were decreased by melatonin treatment, the effect of melatonin on DNA damage response was not a direct consequence of ATM inhibition. Instead, melatonin enhanced DNA repair via nonhomologous end‐joining (NHEJ) pathway. Interestingly, these actions of melatonin on DNA damage response are receptor‐independent in mouse oocytes. Therefore, our results demonstrated that melatonin protects oocytes from DNA damage during prophase arrest by enhancing DNA repair via NHEJ and subsequently prevents the deterioration of oocyte quality during meiotic maturation.
Nonlinear mixed‐effects pharmacokinetic modeling of the novel COX‐2 selective inhibitor vitacoxib in dogs
Authors: Wang Jianzhong , Schneider Benjamin K. , Sun Pan , Gong Xiaohui , Qiu Jicheng , Li Jing , Seo Yeon‐Jung , Mochel Jonathan P. , Cao Xingyuan
Published: August 2019

The objective of this study was to develop a nonlinear mixed‐effects model of vitacoxib disposition kinetics in dogs after intravenous (I.V.), oral (P.O.), and subcutaneous (S.C.) dosing. Data were pooled from four consecutive pharmacokinetic studies in which vitacoxib was administered in various dosing regimens to 14 healthy beagle dogs. Plasma concentration versus time data were fitted simultaneously using the stochastic approximation expectation maximization (SAEM) algorithm for nonlinear mixed‐effects as implemented in Monolix version 2018R2. Correlations between random effects and significance of covariates on population parameter estimates were evaluated using multiple samples from the posterior distribution of the random effects. A two‐compartment mamillary model with first‐order elimination and first‐order absorption after P.O. and S.C. administration, best described the available pharmacokinetic data. Final parameter estimates indicate that vitacoxib has a low‐to‐moderate systemic clearance (0.35 L hr−1 kg−1) associated with a low global extraction ratio, but a large volume of distribution (6.43 L/kg). The absolute bioavailability after P.O. and S.C. administration was estimated at 10.5% (fasted) and 54.6%, respectively. Food intake was found to increase vitacoxib oral bioavailability by a fivefold, while bodyweight (BW) had a significant impact on systemic clearance, thereby confirming the need for BW adjustment with vitacoxib dosing in dogs.
The arts class
Authors: Jones Rhian E
Published: August 2019

Over the past 30 years, political decisions have restricted access to and use of the means of cultural production. What measures could be taken to reverse this and support working‐class creative autonomy?
Japan's nationwide long‐term monitoring survey of seaweed communities known as the “Monitoring Sites 1000”: Ten‐year overview and future perspectives
Authors: Terada Ryuta , Abe Mahiko , Abe Takuzo , Aoki Masakazu , Dazai Akihiro , Endo Hikaru , Kamiya Mitsunobu , Kawai Hiroshi , Kurashima Akira , Motomura Taizo , Murase Noboru , Sakanishi Yoshihiko , Shimabukuro Hiromori , Tanaka Jiro , Yoshida Goro , Aoki Misuzu
Published: August 2019

“Monitoring Sites 1000” – Japan's long‐term monitoring survey was established in 2003, based on the Japanese Government policy for the conservation of biodiversity. Ecological surveys have been conducted on various types of ecosystems at approximately 1000 sites in Japan for 15 years now and are planned to be carried out for 100 years. Since 2008, seaweed communities had been monitored at six sites, featuring the kelp (e.g. Saccharina and Ecklonia; Laminariales) and Sargassum (Fucales) communities in the subarctic and temperate regions of Japan. Annual surveys were carried out during the season when these canopy‐forming seaweeds are most abundant. A non‐destructive quadrat sampling method, with permanent quadrats placed along transects perpendicular to the shoreline, was used to determine species composition, coverage, and vertical distribution of seaweeds at these sites; while destructive sampling was done every 5 years to determine biomass. The occurrence of canopy‐forming species Saccharina japonica (var. japonica) and Ecklonia cava have appeared to be stable at the Muroran (southwestern part of Hokkaido Island) and Shimoda (Pacific coast of middle Honshu Island) sites, respectively; whereas the coverage of Ecklonia radicosa (= Eckloniopsis radicosa) at the Satsuma‐Nagashima site in southern part of Kyushu Island was highly variable until its sudden disappearance from the habitat in 2016. Thalli of E. radicosa lost most of their blades through browsing by herbivorous fish, and thus, this may be one of the causes of the decline. A shift in the community structure related to environmental changes had also been observed at some other sites. Pre‐ and post‐disaster data revealed the impact of the 2011 earthquake and tsunami disasters, including a shift in the vertical distribution of Ecklonia bicyclis (= Eisenia bicyclis) to shallower depths at the Shizugawa site in the Pacific coast of northern Honshu Island, due to seafloor subsidence.
Women Behind the Shutter: Exploring the Place of Women in Elite Environmental Conservation Photographer Networks
Authors: Whitley Cameron Thomas , Kalof Linda
Published: August 2019

Since the 1980s, much has been written about the importance of including women in environmental decision making. However, when and how women are included remains an issue. The goal of this article was to explore how the historical exclusion of women from the production of conservation visual narratives continues to have an influence on conservation networks. We surveyed 121 National Geographic Society‐affiliated conservation/wildlife photographers, which produced a usable sample of 98 photographers, to assess whether there is evidence of the historical legacy of female exclusion in contemporary elite conservation photography networks. Using network analysis, we find a strong network among 67 conservation photographers, with eight subgroups. Our analysis shows that there are formal networks among conservation photographers, but these networks are sparsely populated with women. Of the women who are present, they mostly engage in the same subnetworks. Our findings provide evidence to support the notion that the historical exclusion of women from the production of visual conservation narratives has had a lasting impact on the network of conservation image producers, which may influence the way conservation is depicted to the general public. We situate our findings using gendered organizational theory.
Copper blocks V‐ATPase activity and SNARE complex formation to inhibit yeast vacuole fusion
Authors: Miner Gregory E. , Sullivan Katherine D. , Zhang Chi , Hurst Logan R. , Starr Matthew L. , Rivera‐Kohr David A. , Jones Brandon C. , Guo Annie , Fratti Rutilio A.
Published: August 2019

The accumulation of copper in organisms can lead to altered functions of various pathways and become cytotoxic through the generation of reactive oxygen species. In yeast, cytotoxic metals such as Hg+, Cd2+ and Cu2+ are transported into the lumen of the vacuole through various pumps. Copper ions are initially transported into the cell by the copper transporter Ctr1 at the plasma membrane and sequestered by chaperones and other factors to prevent cellular damage by free cations. Excess copper ions can subsequently be transported into the vacuole lumen by an unknown mechanism. Transport across membranes requires the reduction of Cu2+ to Cu+. Labile copper ions can interact with membranes to alter fluidity, lateral phase separation and fusion. Here we found that CuCl2 potently inhibited vacuole fusion by blocking SNARE pairing. This was accompanied by the inhibition of V‐ATPase H+ pumping. Deletion of the vacuolar reductase Fre6 had no effect on the inhibition of fusion by copper. This suggests that Cu2+ is responsible for the inhibition of vacuole fusion and V‐ATPase function. This notion is supported by the differential effects of chelators. The Cu2+‐specific chelator triethylenetetramine rescued fusion, whereas the Cu+‐specific chelator bathocuproine disulfonate had no effect on the inhibited fusion.
Administration of certain sedative drugs is associated with variation in sonographic and radiographic splenic size in healthy cats
Authors: Auger Mylène , Fazio Constance , de Swarte Marie , Bussières Geneviève , Schaefer Deanna , Springer Cary M.
Published: August 2019

Ultrasonography and radiography are standard diagnostic tests for cats with suspected splenic disease, however published information on outside sources of variation are currently lacking. The purpose of this prospective, randomized, crossover group study was to evaluate effects of common sedative drugs on the sonographic and radiographic characteristics of the spleen in healthy cats. Fifteen healthy adult research cats were randomly assigned into one of three groups corresponding to different sequences of administration of five sedative drugs/drug combinations (acepromazine; butorphanol; dexmedetomidine; midazolam and butorphanol (MB); and dexmedetomidine, butorphanol, and ketamine (DBK)), administered at 1‐week intervals. At each visit, three‐view abdominal radiographic and ultrasonographic examinations were performed prior to sedation and repeated 15‐30 min and 2‐3 h post sedation. Two board‐certified radiologists (one ACVR and one ACVR/ECVDI) evaluated the anonymized and randomized images. Acepromazine resulted in significantly increased sonographic and radiographic splenic measurements from baseline, which remained significantly increased 2‐3 h post sedation. The mean magnitude of this change ranged from 0.9 mm (tail height, SD 1.4 mm) to 1.8 mm (body height, SD 1.7 mm) for ultrasound, and was 2.2 mm (ventrodorsal width, SD 2.3 mm) for radiographs. With butorphanol, there was no significant change in splenic size. For dexmedetomidine, MB, and DBK, there was a trend toward increased splenic size from baseline to the first post‐sedation timepoint, which was statistically significant for radiographic measurements, although not for ultrasound. Findings indicated that acepromazine should be avoided prior to imaging while butorphanol may be used when sedation is needed in cats presenting for potential splenic disease.
Focused Ultrasound Ablation for the Treatment of Patients With Localized Deformed Breast Cancer: Computer Simulation
Authors: Montienthong Prempreeya , Rattanadecho Phadungsak
Published: August 2019

This paper is carried out on the computer simulation of breast cancer treated using a high intensity focused ultrasound (HIFU). The mathematical models consist of the pressure acoustics equation, bioheat equation, heat transfer in a blood vessel, momentum equations in a blood vessel, and mechanical deformation equation. In the numerical simulation, these mathematical models are solved by using an axisymmetric finite element method (FEM) with time-dependent, thermal and acoustic properties to describe the temperature distribution and the total displacement in tissue. The comparison of the simulated results in the model with two sizes of the cancer tumor and two frequencies of ultrasound are also considered in order to approach realistic tissue modeling. The results show that the breast cancer model with deformation, which is the more accurate way to simulate the physical characteristics of therapeutic breast cancer compared to the literature results, hence leads to more useful in the medical approach and this study was conducted to prevent errors caused by inaccurate focal points.
Preliminary Evidence That Motor Planning Is Slower and More Difficult for Children With Autism Spectrum Disorder During Motor Cooperation
Authors: Studenka Breanna E. , Myers Kodey
Published: August 2019

Children with autism spectrum disorder (ASD) exhibit impairment in helping someone else with a motor action, which may arise from impairment in selecting and preparing motor responses. Five children with ASD and five typically developing children performed a cooperative motor planning task that required them to reach for, lift, and hand an object (hammer or stick) to a researcher. The response, movement, and grasp time were measured. Children with ASD grasped the object longer on trials where they helped, indicating that the action was planned in sequence versus as a whole (i.e., prior to the onset of movement). The hammer object elicited a quicker response than the stick, suggesting the facilitation of planning by tools with inherent action properties. Finally, the increased helping of children with ASD was not mirrored by changes in the response, movement, or grasp time.
NIH fetal tissue research requirements raise worries
Authors: Kaiser Jocelyn , Wadman Meredith
Published: August 2019

Biomedical studies on Zika virus, AIDS, and more imperiled.
Fossils show large predator prowled Cambrian sediments
Authors: Sokol Joshua
Published: August 2019

"Millennium Falcon" stirs up ideas about ecosystems at the dawn of animal life, 500 million years ago.
Brexit backer Boris Johnson stokes fears for U.K. scientists
Authors: Stokstad Erik
Published: August 2019

Prime minister's hardline stance increases odds of a "no-deal" divorce from the European Union.
The CRISPR animal kingdom
Authors: Cohen Jon
Published: August 2019

China has used the genome editor more aggressively, on more species, than any other country.
Targeting transmissible cancers in animals
Authors: Patchett Amanda , Woods Gregory
Published: August 2019

New understanding of Tasmanian devil facial tumors informs therapy and prevention
A FRESH SLATE for 3D bioprinting
Authors: Dasgupta Queeny , Black Lauren D.
Published: August 2019

Greater structural complexity has been achieved in additive manufacturing of biomaterials
The dark side of the Moon—and science
The Women of the Moon
Daniel R. Altschuler and Fernando J. Ballesteros
Oxford University Press, 2019. 336 pp.
Authors: Gibson Emily K.
Published: August 2019

Tales of the 28 lunar craters named for women offer a chance to reflect on women's struggle for scientific recognition
Toll-Like Receptor 3 Deficiency Leads to Altered Immune Responses to Chlamydia trachomatis Infection in Human Oviduct Epithelial Cells
Authors: Xu Jerry Z. , Kumar Ramesh , Gong Haoli , Liu Luyao , Ramos-Solis Nicole , Li Yujing , Derbigny Wilbert A.
Published: August 2019

Reproductive tract pathology caused by
Chlamydia trachomatis
infection is an important global cause of human infertility. To better understand the mechanisms associated with
Chlamydia
-induced genital tract pathogenesis in humans, we used CRISPR genome editing to disrupt Toll-like receptor 3 (TLR3) function in the human oviduct epithelial (hOE) cell line OE-E6/E7 in order to investigate the possible role(s) of TLR3 signaling in the immune response to
Chlamydia
.
Analysis of
Brevundimonas subvibrioides
Developmental Signaling Systems Reveals Inconsistencies between Phenotypes and c-di-GMP Levels
Authors: Sperling Lauryn , Mulero Alegría Milagros D. , Kaever Volkhard , Curtis Patrick D.
Published: August 2019

Cyclic di-GMP and associated signaling proteins are widespread in bacteria, but their role in physiology is often complex and difficult to predict through genomic level analyses. In
C. crescentus
, c-di-GMP has been integrated into the developmental cell cycle, but there is increasing evidence that environmental factors can impact this system as well. The research presented here suggests that the integration of these signaling networks could be more complex than previously hypothesized, which could have a bearing on the larger field of c-di-GMP signaling. In addition, this work further reveals similarities and differences in a conserved regulatory network between organisms in the same taxonomic family, and the results show that gene conservation does not necessarily imply close functional conservation in genetic pathways.
Evaluation of an In-House Colistin NP Test for Use in Resource-Limited Settings
Authors: Mitton B. , Kingsburgh C. , Kock M. M. , Mbelle N. M. , Strydom K.
Published: August 2019

Colistin has become increasingly important in the treatment of multidrug-resistant Gram-negative bacteria. Resistance to colistin has emerged globally, necessitating the need for an accurate method to detect colistin resistance. The colistin NP test has shown promise as a rapid screening assay for colistin resistance.
Genetic predisposition to increased serum calcium, bone mineral density, and fracture risk in individuals with normal calcium levels: mendelian randomisation study
Authors: Cerani Agustin , Zhou Sirui , Forgetta Vincenzo , Morris John A , Trajanoska Katerina , Rivadeneira Fernando , Larsson Susanna C , Michaëlsson Karl , Richards J Brent
Published: August 2019

Objective

To determine if genetically increased serum calcium levels are associated with improved bone mineral density and a reduction in osteoporotic fractures.

Design

Mendelian randomisation study.

Setting

Cohorts used included: the UK Biobank cohort, providing genotypic and estimated bone mineral density data; 25 cohorts from UK, USA, Europe, and China, providing genotypic and fracture data; and 17 cohorts from Europe, providing genotypic and serum calcium data (summary level statistics).

Participants

A genome-wide association meta-analysis of serum calcium levels in up to 61 079 individuals was used to identify genetic determinants of serum calcium levels. The UK Biobank study was used to assess the association of genetic predisposition to increased serum calcium with estimated bone mineral density derived from heel ultrasound in 426 824 individuals who had, on average, calcium levels in the normal range. A fracture genome-wide association meta-analysis comprising 24 cohorts and the UK Biobank including a total of 76 549 cases and 470 164 controls, who, on average, also had calcium levels in the normal range was then performed.

Results

A standard deviation increase in genetically derived serum calcium (0.13 mmol/L or 0.51 mg/dL) was not associated with increased estimated bone mineral density (0.003 g/cm
2
, 95% confidence interval −0.059 to 0.066; P=0.92) or a reduced risk of fractures (odds ratio 1.01, 95% confidence interval 0.89 to 1.15; P=0.85) in inverse-variance weighted mendelian randomisation analyses. Sensitivity analyses did not provide evidence of pleiotropic effects.

Conclusions

Genetic predisposition to increased serum calcium levels in individuals with normal calcium levels is not associated with an increase in estimated bone mineral density and does not provide clinically relevant protection against fracture. Whether such predisposition mimics the effect of short term calcium supplementation is not known. Given that the same genetically derived increase in serum calcium is associated with an increased risk of coronary artery disease, widespread calcium supplementation in the general population could provide more risk than benefit.
Fish and marine fatty acids intakes, theFADSgenotypes and long-term weight gain: a prospective cohort study
Authors: Huang Tao , Wang Tiange , Heianza Yoriko , Wiggs Janey , Sun Dianjianyi , Choi Hyon-Kyoo , Chai Jin Fang , Sim Xueling , Khor Chiea Chuen , Friedlander Yechiel , Chan Andrew T , Curhan Gary , Vivo Immaculata De , van Dam Rob Martinu , Heng Chew Kiat , Fuchs Charles , Pasquale Louis R , Yuan Jian-min , Hu Frank B , Koh Woon Puay , Qi Lu
Published: August 2019

Objective

We tested whether genetic variants near fatty acid desaturases gene (FADS) cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet, interacted with these dietary factors on change in body mass index (BMI).

Design

ThreeFADSvariants were examined for gene-diet interactions on long-term (~10 years) changes in BMI and body weight in four prospective cohort studies.

Setting

Population based study.

Participants

11 323 women from the Nurses’ Health Study (NHS), 6833 men from the Health Professionals Follow-up Study (HPFS) and replicated in 6254 women from the Women’s Health Initiative (WHI) and 5 264 Chinese from the Singapore Chinese Health Study (SCHS).

Main outcomes

Long-term (~10 years) changes in BMI and body weight.

Results

In the NHS and HPFS cohorts, food-sourced n-3 PUFAs intake showed interactions with theFADSrs174570 on changes of BMI (P for interaction=0.02 in NHS, 0.05 in HPFS and 0.007 in combined). Such interactions were replicated in two independent cohorts WHI and SCHS (P for interaction=0.04 in WHI, 0.02 in SCHS and 0.001 in combined). The genetic associations of theFADSrs174570 with changes in BMI increased across the tertiles of n-3 PUFAs in all the cohorts. Fish intake also accentuated the genetic associations of theFADSrs174570 with long-term changes in BMI (pooled P for interaction=0.006). Viewed differently, long chain n-3 PUFAs intake showed stronger association with long-term changes in BMI among the rs174570 T carriers (beta=0.79 kg/m2per g, p=3×10−5) than the rs174570 non-T carriers (beta=0.16 kg/m2per g, p=0.08). Similar results were observed for fish intake.

Conclusions

Our hypothesis-driven analyses provide replicable evidence that long chain n-3 PUFAs and fish intakes may interact with theFADSvariant on long-term weight gain. Further investigation is needed to confirm our findings in other cohorts.
What factors influence community wound care in the UK? A focus group study using the Theoretical Domains Framework
Authors: Gray Trish A , Wilson Paul , Dumville Jo C , Cullum Nicky A
Published: August 2019

Objectives

Research has found unwarranted variation across community wound care services in the North of England, with underuse of evidence-based practice and overuse of interventions where there is little or no known patient benefit. This study explored the factors that influence care in community settings for people with complex wounds, to develop a deeper understanding of the current context of wound care and variation in practice.

Design

Qualitative focus group study using the Theoretical Domains Framework (TDF) to structure the questions, prompts and analyses.

Setting

Community healthcare settings in the North of England, UK.

Participants

Forty-six clinical professionals who cared for patients with complex wounds and eight non-clinical professionals who were responsible for procuring wound care products participated across six focus group interviews.

Results

We found the TDF domains: environmental context and resources, knowledge, skills, social influences and behaviour regulation to best explain the variation in wound care and the underuse of research evidence. Factors such as financial pressures were perceived as having a negative effect on the continuity of care, the availability of wound care services and workloads. We found practice to be mainly based on experiential knowledge and personal preference and highly influenced by colleagues, patients and the pharmaceutical industry, although not by research evidence.

Conclusions

Our study provides new insight into the role that experiential learning and social influences play in determining wound care and on the limited influence of research. Workforce pressures and limited resources are perceived to impede care by reducing patient access to services and the ability to provide holistic care. Participative collaboration between university and healthcare organisations may offer a supportive route to addressing issues, implementing sustainable changes to practice and service delivery and a resolute commitment to research use among clinical professionals.
Socioeconomic determinants of out-of-pocket pharmaceutical expenditure among middle-aged and elderly adults based on the China Health and Retirement Longitudinal Survey
Authors: Du Jinglin , Yang Xue , Chen Mingsheng , Wang Zhonghua
Published: August 2019

Objective

Out-of-pocket pharmaceutical expenditure (OOPPE) is a considerable burden for middle-aged and elderly adults due to their high prevalence of diseases, insufficient income and absence of medical insurance in China. The objective of this study was to assess the determinants of OOPPE among Chinese middle-aged and elderly adults.

Methods

This is a cross-sectional study based on the China Health and Retirement Longitudinal Survey conducted in 2015. The Andersen behavioural health model was used to select the factors. Binary multivariable logistic and generalised linear regressions were both applied to examine the determinants of OOPPE.

Results

Of the respondents, 15.28%, 5.20% and 51.35% reported an OOPPE for outpatient services, inpatient services and self-medication, respectively. The OOPPE for outpatient services, inpatient services and self-medication was US$6.66, US$17.93 and US$15.32, respectively. Increased age significantly influenced the likelihood of OOPPE, and older people (aged >65 years) had lower OOPPE for outpatient services. Having health insurance significantly reduced the likelihood of OOPPE for outpatient and inpatient services but increased OOPPE for self-medication. In general, compared with the low-income group, higher income groups had a significantly lower likelihood of having an OOPPE, and when they did the amounts were less. Generally, middle-aged and elderly people with poor self-reported health status, limitation of daily activities, and critical or chronic diseases had a significantly higher likelihood of having an OOPPE and at a significantly higher amount.

Conclusion

Policy-making efforts should focus on reducing self-medication OOPPE and alleviating its associated socioeconomic determinants to ease the economic burden of diseases among middle-aged and elderly adults in China.
Nutrition and Exercise in Critical Illness Trial (NEXIS Trial): a protocol of a multicentred, randomised controlled trial of combined cycle ergometry and amino acid supplementation commenced early during critical illness
Authors: Heyland Daren K , Day Andrew , Clarke G John , Hough Catherine (Terri) , Files D Clark , Mourtzakis Marina , Deutz Nicolaas , Needham Dale M , Stapleton Renee
Published: August 2019

Introduction

Survivors of critical illness often experience significant morbidities, including muscle weakness and impairments in physical functioning. This muscle weakness is associated with longer duration mechanical ventilation, greater hospital costs and increased postdischarge impairments in physical function, quality of life and survival. Compared with standard of care, the benefits of greater protein intake combined with structured exercise started early after the onset of critical illness remain uncertain. However, the combination of protein supplementation and exercise in other populations has demonstrated positive effects on strength and function. In the present study, we will evaluate the effects of a combination of early implementation of intravenous amino acid supplementation and in-bed cycle ergometry exercise versus a ‘usual care’ control group in patients with acute respiratory failure requiring mechanical ventilation in an intensive care unit (ICU).

Methods and analysis

In this multicentre, assessor-blinded, randomised controlled trial, we will randomise 142 patients in a 1:1 ratio to usual care (which commonly consists of minimal exercise and under-achievement of guideline-recommended caloric and protein intake goals) versus a combined intravenous amino acid supplementation and in-bed cycle ergometery exercise intervention. We hypothesise that this novel combined intervention will (1) improve physical functioning at hospital discharge; (2) reduce muscle wasting with improved amino acid metabolism and protein synthesis in-hospital and (3) improve patient-reported outcomes and healthcare resource utilisation at 6 months after enrolment. Key cointerventions will be standardised. In-hospital outcome assessments will be conducted at baseline, ICU discharge and hospital discharge. An intent-to-treat analysis will be used to analyse all data with additional per-protocol analyses.

Ethics and dissemination

The trial received ethics approval at each institution and enrolment has begun. These results will inform both clinical practice and future research in the area. We plan to disseminate trial results in peer-reviewed journals, at national and international conferences, and via nutritional and rehabilitation-focused electronic education and knowledge translation platforms.

Trial registration number

NCT03021902; Pre-results.
Joint contribution of socioeconomic circumstances and ethnic group to variations in preterm birth, neonatal mortality and infant mortality in England and Wales: a population-based retrospective cohort study using routine data from 2006 to 2012
Authors: Opondo Charles , Gray Ron , Hollowell Jennifer , Li Yangmei , Kurinczuk Jennifer J , Quigley Maria A
Published: August 2019

Objectives

This study aimed to describe the variation in risks of adverse birth outcomes across ethnic groups and socioeconomic circumstances, and to explore the evidence of mediation by socioeconomic circumstances of the effect of ethnicity on birth outcomes.

Setting

England and Wales.

Participants

The data came from the 4.6 million singleton live births between 2006 and 2012.

Exposure

The main exposure was ethnic group. Socioeconomic circumstances, the hypothesised mediator, were measured using the Index of Multiple Deprivation (IMD), an area-level measure of deprivation, based on the mother’s place of residence.

Primary and secondary outcome measures

The primary outcomes were birth outcomes, namely: neonatal death, infant death and preterm birth. We estimated the slope and relative indices of inequality to describe differences in birth outcomes across IMD, and the proportion of the variance in birth outcomes across ethnic groups attributable to IMD. We investigated mediation by IMD on birth outcomes across ethnic groups using structural equation modelling.

Results

Neonatal mortality, infant mortality and preterm birth risks were 2.1 per 1000, 3.2 per 1000 and 5.6%, respectively. Babies in the most deprived areas had 47%–129% greater risk of adverse birth outcomes than those in the least deprived areas. Minority ethnic babies had 48%–138% greater risk of adverse birth outcomes compared with white British babies. Up to a third of the variance in birth outcomes across ethnic groups was attributable to differences in IMD, and there was strong statistical evidence of an indirect effect through IMD in the effect of ethnicity on birth outcomes.

Conclusion

There is evidence that socioeconomic circumstances could be contributing to the differences in birth outcomes across ethnic groups.
Beliefs and challenges held by medical staff about providing emergency care to migrants: an international systematic review and translation of findings to the UK context
Authors: Harrison Hooi-Ling , Daker-White Gavin
Published: August 2019

Objective

Migration has increased globally. Emergency departments (EDs) may be the first and only contact some migrants have with healthcare. Emergency care providers’ (ECPs) views concerning migrant patients were examined to identify potential health disparities and enable recommendations for ED policy and practice.

Design

Systematic review and meta-synthesis of published findings from qualitative studies.

Data sources

Electronic databases (Ovid Medline, Embase (via Ovid), PsycINFO (via OVID), CINAHL, Web of Science and PubMed), specialist websites and journals were searched.

Eligibility criteria

Studies employing qualitative methods published in English.

Settings

EDs in high-income countries.

Participants

ECPs included doctors, nurses and paramedics.

Topic of enquiry

Staff views on migrant care in ED settings.

Data extraction and synthesis

Data that fit the overarching themes of ‘beliefs’ and ‘challenges’ were extracted and coded into an evolving framework. Lines of argument were drawn from the main themes identified in order to infer implications for UK policy and practice.

Results

Eleven qualitative studies from Europe and the USA were included. Three analytical themes were found: challenges in cultural competence; weak system organisation that did not sufficiently support emergency care delivery; and ethical dilemmas over decisions on the rationing of healthcare and reporting of undocumented migrants.

Conclusion

ECPs made cultural and organisational adjustments for migrant patients, however, willingness was dependent on the individual’s clinical autonomy. ECPs did not allow legal status to obstruct delivery of emergency care to migrant patients. Reported decisions to inform the authorities were mixed; potentially leading to uncertainty of outcome for undocumented migrants and deterring those in need of healthcare from seeking treatment. If a charging policy for emergency care in the UK was introduced, it is possible that ECPs would resist this through fears of widening healthcare disparities. Further recommendations for service delivery involve training and organisational support.
Incidental findings on brain imaging and blood tests: results from the first phase of Insight 46, a prospective observational substudy of the 1946 British birth cohort
Authors: Keuss Sarah E , Parker Thomas D , Lane Christopher A , Hoskote Chandrashekar , Shah Sachit , Cash David M , Keshavan Ashvini , Buchanan Sarah M , Murray-Smith Heidi , Wong Andrew , James Sarah-Naomi , Lu Kirsty , Collins Jessica , Beasley Daniel G , Malone Ian B , Thomas David L , Barnes Anna , Richards Marcus , Fox Nick , Schott Jonathan M
Published: August 2019

Objective

To summarise the incidental findings detected on brain imaging and blood tests during the first wave of data collection for the Insight 46 study.

Design

Prospective observational sub-study of a birth cohort.

Setting

Single-day assessment at a research centre in London, UK.

Participants

502 individuals were recruited from the MRC National Survey of Health and Development (NSHD), the 1946 British birth cohort, based on pre-specified eligibility criteria; mean age was 70.7 (SD: 0.7) and 49% were female.

Outcome measures

Data regarding the number and types of incidental findings were summarised as counts and percentages, and 95% confidence intervals were calculated.

Results

93.8% of participants completed a brain scan (n=471); 4.5% of scanned participants had a pre-defined reportable abnormality on brain MRI (n=21); suspected vascular malformations and suspected intracranial mass lesions were present in 1.9% (n=9) and 1.5% (n=7) respectively; suspected cerebral aneurysms were the single most common vascular abnormality, affecting 1.1% of participants (n=5), and suspected meningiomas were the most common intracranial lesion, affecting 0.6% of participants (n=3); 34.6% of participants had at least one abnormality on clinical blood tests (n=169), but few reached the prespecified threshold for urgent action (n=11).

Conclusions

In older adults, aged 69-71 years, potentially serious brain MRI findings were detected in around 5% of participants, and clinical blood test abnormalities were present in around one third of participants. Knowledge of the expected prevalence of incidental findings in the general population at this age is useful in both research and clinical settings.
Enablers and barriers to treatment adherence in heterozygous familial hypercholesterolaemia: a qualitative evidence synthesis
Authors: Kinnear Fiona J , Wainwright Elaine , Perry Rachel , Lithander Fiona E , Bayly Graham , Huntley Alyson , Cox Jennifer , Shield Julian PH , Searle Aidan
Published: August 2019

Objectives

Individuals with heterozygous familial hypercholesterolaemia (FH) are at high risk of developing cardiovascular disease (CVD). This risk can be substantially reduced with lifelong pharmacological and lifestyle treatment; however, research suggests adherence is poor. We synthesised the qualitative research to identify enablers and barriers to treatment adherence.

Design

This study conducted a thematic synthesis of qualitative studies.

Data sources

MEDLINE, Embase, PsycINFO via OVID, Cochrane library and CINAHL databases and grey literature sources were searched through September 2018.

Eligibility criteria

We included studies conducted in individuals with FH, and their family members, which reported primary qualitative data regarding their experiences of and beliefs about their condition and its treatment.

Data extraction and synthesis

Quality assessment was undertaken using the Critical Appraisal Skills Programme for qualitative studies. A thematic synthesis was conducted to uncover descriptive and generate analytical themes. These findings were then used to identify enablers and barriers to treatment adherence for application in clinical practice.

Results

24 papers reporting the findings of 15 population samples (264 individuals with FH and 13 of their family members) across 8 countries were included. Data captured within 20 descriptive themes were considered in relation to treatment adherence and 6 analytical themes were generated: risk assessment; perceived personal control of health; disease identity; family influence; informed decision-making; and incorporating treatment into daily life. These findings were used to identify seven enablers (eg, ‘commencement of treatment from a young age’) and six barriers (eg, ‘incorrect and/or inadequate knowledge of treatment advice’) to treatment adherence. There were insufficient data to explore if the findings differed between adults and children.

Conclusions

The findings reveal several enablers and barriers to treatment adherence in individuals with FH. These could be used in clinical practice to facilitate optimal adherence to lifelong treatment thereby minimising the risk of CVD in this vulnerable population.

PROSPERO registration number

CRD42018085946.