bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet mass index and prediction of severity of transient tachypnea of the newborn
Authors: Ilhan Ozkan , Bor Meltem
Published: May 2019

Background

Platelet mass index (PMI) is associated with platelet functionality. The aim of this study was to evaluate the role of PMI in predicting the severity of transient tachypnea of the newborn (TTN).

Methods

Infants with gestational age ≥37 weeks and birthweight ≥2,000 g who were given nasal intermittent mandatory ventilation for TTN ≤6 h after birth were retrospectively enrolled in this study. PMI was calculated using the following formula: PMI = platelet count × mean platelet volume/103 (fL/nL). The study infants (n = 101) were divided into two groups according to the duration of tachypnea: ≤48 h (n = 45) and >48 h (n = 56).

Results

The PMI and platelet count were significantly lower in the group with tachypnea duration >48 h than in the tachypnea duration ≤48 h group (P < 0.001 and P = 0.04, respectively). A negative significant correlation was noted between PMI and the duration of tachypnea (r = −0.43, P < 0.001). A PMI cut‐off of 1,562 fL/nL can predict prolonged tachypnea (>48 h) with a sensitivity of 62.5%, specificity of 68.9%, positive predictive value of 71.4%, and negative predictive value of 59.6% (area under the curve, 0.682 ± 0.053; P = 0.002).

Conclusions

Lower PMI and lower platelet count are associated with longer duration of tachypnea in patients with TTN.
A four‐dimensional agent‐based model: A case study of forest‐fire smoke propagation
Authors: Smith Alex K. , Dragićević Suzana
Published: May 2019

Dynamic geospatial complex systems are inherently four‐dimensional (4D) processes and there is a need for spatio‐temporal models that are capable of realistic representation for improved understanding and analysis. Such systems include changes of geological structures, dune formation, landslides, pollutant propagation, forest fires, and urban densification. However, these phenomena are frequently analyzed and represented with modeling approaches that consider only two spatial dimensions and time. Consequently, the main objectives of this study are to design and develop a modeling framework for 4D agent‐based modeling, and to implement the approach to the 4D case study for forest‐fire smoke propagation. The study area is central and southern British Columbia and the western parts of Alberta, Canada for forest fires that occurred in the summer season of 2017. The simulation results produced realistic spatial patterns of the smoke propagation dynamics.
A variant inOLFML3is associated with pectinate ligament abnormality and primary closed‐angle glaucoma in Border Collies from the United Kingdom
Authors: Oliver James A. C. , Wright Hattie , Massidda Paola A. , Burmeister Louise M. , Mellersh Cathryn S.
Published: May 2019

Purpose

Canine primary closed‐angle glaucoma (PCAG) is a complex disease caused by multiple genetic factors. A c.590G>A variant inOLFML3was recently reported to be a candidate for pectinate ligament abnormality (PLA) and PCAG in the Border Collie. We investigated the association of this variant with PLA and PCAG in Border Collies from the United Kingdom.

Methods

TheOLFML3variant was genotyped in 106 Border Collies comprising 90 with normal eyes (controls) and 16 with PLA (n = 11) and/or PCAG (n = 5) (cases). Genotyping was performed in an additional 103 Border Collies to estimate variant frequency within the population. To investigate the association of the variant with disease in other breeds, genotyping was performed in 337 non‐Border Collies with PLA and/or PCAG.

Results

Of the 90 controls, 71 were homozygous for the wild‐type allele, two were homozygous for the variant, and 17 were heterozygous. Of the 16 cases, three were homozygous for the wild‐type allele, 11 were homozygous for the variant, and two were heterozygous. The association of the variant allele with disease was significant (P = 1.1 x 10−9). We estimated the frequency of this variant to be 4.4% within the United Kingdom Border Collie population, and it was not identified in clinically affected dogs of any other breed.

Conclusions

This study confirms the association of theOLFML3variant with PLA and PCAG in Border Collies from the United Kingdom. DNA testing for the variant and selective breeding can reasonably be expected to result in a reduction of PLA and PCAG prevalence in the breed.
How Stapes Ankylosis and Fracture Affect Middle Ear Dynamics: A Numerical Study
Authors: Lobato Lucas , Paul Stephan , Cordioli Júlio , Cruz Oswaldo L. M.
Published: May 2019

Numerical models of the human middle ear have been developed throughout the last 30 years, for different purposes. While several types of pathologies have been studied, stapedial disorders were seldomly explored. This papers aims to clarify how stapes fracture and some forms of stapes ankylosis, such as stapedial tendon (ST) ossification, augmented pyramidal eminence (PE) and bony bar presence, affect the sound transmission through the middle ear. In addition, the stapes dynamics is also analyzed by means of total displacement and first principal strain. For the purpose of the study, first, a three-dimensional finite element model of the human middle ear is detailed and validated under normal (healthy) conditions. The model is then modified to represent the stapedial disorders of interest. A measure is established for evaluating how the disorders reduce sound transmission through the middle ear. Results of the reduction of sound transmission showed that the different forms of stapes ankylosis affect primarily low frequencies, while the stapes fracture mostly affects high frequency sound transmission. According to the results, an augmented PE does not restrict stapes movement unless followed by some ossification of the ST. In addition, the question whether the fracture is in the anterior or posterior crus and the distance of the fractured part from the stapes footplate have a relevant role in the reduction of the sound transmission. Finally, the analysis of total displacement and first principal strain of the stapes helped to highlight some differences among the stapedial disorders.
First and Second Law Analyses of Double Effect Parallel and Series Flow Direct Fired Absorption Cycles for Optimum Operating Parameters
Authors: Azhar Md. , Siddiqui M. Altamush
Published: May 2019

Thermodynamic analysis of double effect parallel and series flow direct fired absorption systems with lithium bromide–water has been carried out for different operating conditions. Temperatures in primary generator (Tg) and secondary generator (Tgs)/secondary condenser (Tcs) are optimized analytically using an iterative technique for maximum coefficient of performance (COP) and minimum energy required. A solution distribution ratio for a parallel flow cycle is also optimized. Source of energy used to drive the cycles is considered as compressed natural gas (CNG) and liquefied petroleum gas (LPG). Exergy destruction rate (EDR) in individual components as well as in the whole cycle along with volume flow rate of LPG and CNG is presented and compared. Results show that maximum COP for the parallel flow cycle is 3–6% higher than the series flow cycle. Also, minimum EDR of the parallel flow cycle is around 4% less while energy consumption is 2–3% low as compared to the series flow cycle.
Effect of annealing on the surface characteristics of α-Al2O3(0001) probed by XPS
Authors: Geetha Ganga Babu , Dansou Carmel , Carleschi Emanuela , Doyle Bryan P.
Published: May 2019

α-Al2O3(0001) is a technologically important metal oxide substrate used in current solid state electronic devices. This report presents the effect of heat treatment on the surface electronic structure characteristics of α-Al2O3(0001) substrates examined by x-ray photoelectron spectroscopy. Survey spectra, O 1s, Al 2p, Al 2s core levels, and valence band spectra are presented for the as received, vacuum annealed, and oxygen annealed substrates. Annealing removes various contaminants such as C, Zn, and OH groups from the surface, and a sharp (1 × 1) low energy electron diffraction pattern confirms the ordered hexagonal periodicity of the surface. No substantial differences in the valence band spectra are observed due to annealing and suggest that the (1 × 1) surface characteristics of α-Al2O3(0001) are preserved during the surface cleaning procedures.
Cl2/Ar based atomic layer etching of AlGaN layers
Authors: Aroulanda Sébastien , Patard Olivier , Altuntas Philippe , Michel Nicolas , Pereira Jorge , Lacam Cédric , Gamarra Piero , Delage Sylvain L. , Defrance Nicolas , de Jaeger Jean-Claude , Gaquière Christophe
Published: May 2019

This paper reports on atomic layer etching of several III-N materials such as GaN, AlN, AlGaN, and InAlGaN based on a sequential surface modification by chlorine adsorption followed by a low energy Ar plasma exposure to remove the modified layer using a reactive ion etching system. A study on the influence of several parameters, such as gas flow rates, removal step duration, RIE power and number of cycles on the etch per cycle, and the root-mean-square roughness, is performed. Low etch per cycle from 0.17 to 1.85 nm/cycle, respectively, for AlGaN and GaN and surfaces as smooth as the as-grown samples were obtained. The developed process is intended to be used for normally off GaN-based high electron mobility transistor processing.
Remote plasma-assisted low-temperature large-area graphene synthesis
Authors: Pae Jian Yi , Medwal Rohit , Vas Joseph Vimal , Matham Murukeshan Vadakke , Rawat Rajdeep Singh
Published: May 2019

Graphene is typically grown using thermal chemical vapor deposition (CVD) on metallic substrates such as copper and nickel at elevated temperatures above 1000 °C. The synthesis of large-area graphene at low temperature is highly desirable for large volume industrial production. In this paper, the authors report a remote plasma-assisted CVD graphene synthesis at a reduced temperature of 600 °C in a relatively shorter duration of 15 min. Scanning electron microscopy reveals the formation of large graphene crystal with an approximate size of 100 × 100 μm2 over the entire 2 × 10 cm2 surface of copper foil substrates. Raman spectra recorded for graphene grown at 600 °C show the presence of a graphene characteristic “2D” peak, attesting to the formation of graphene. The results show that it is possible to grow horizontal graphene at low temperatures and transfer it to flexible polyethylene terephthalate substrates. The utility of the synthesized graphene is ascertained through the successful fabrication of a flexible graphene-based electrochemical sensor for the detection of glucose concentration. The present research will have a direct impact on flexible wearable biosensors.
Development of a New Tool for Managing Performance Nutrition: The Athlete Food Choice Questionnaire
Authors: Thurecht Rachael L. , Pelly Fiona E.
Published: May 2019

This study aimed to develop and refine an Athlete Food Choice Questionnaire (AFCQ) to determine the key factors influencing food choice in an international cohort of athletes. A questionnaire that contained 84 items on a 5-point frequency scale was developed for this study. Athletes at the 2017 Universiade, in Taiwan, were invited to participate. Principal component analysis was utilized to identify key factors and to refine the questionnaire. Completed questionnaires were received from 156 athletes from 31 countries and 17 sports. The principal component analysis extracted 36 items organized into nine factors explaining 68.0% of variation. The nine factors were as follows: nutritional attributes of the food, emotional influences, food and health awareness, influence of others, usual eating practices, weight control, food values and beliefs, sensory appeal, and performance. The overall Kaiser–Meyer–Olkin measure was 0.75, the Bartlett test of sphericity was statistically significant, χ2(666) =2,536.50, p < .001, and all of the communalities remained >0.5. Intercorrelations were detected between performance and both nutritional attributes of the food and weight control. The price of food, convenience, and situational influences did not form part of the factorial structure. This research resulted in an AFCQ that includes factors specific to athletic performance and the sporting environment. The AFCQ will enable researchers and sports dietitians to better tailor nutrition education and dietary interventions to suit the individual or team. The next phase will test the accuracy and reliability of the AFCQ both during and outside of competition. The AFCQ is a useful tool to assist with management of performance nutrition for athletes.
Acute Effects of Hip Mobilization With Movement Technique on Pain and Biomechanics in Females With Patellofemoral Pain: A Randomized, Placebo-Controlled Trial
Authors: Nunes Guilherme S. , Wolf Débora Faria , dos Santos Daniel Augusto , de Noronha Marcos , Serrão Fábio Viadanna
Published: May 2019

Context: People with patellofemoral pain (PFP) present altered lower-limb movements during some activities. Perhaps, joint misalignment in the hip is one of the reasons for altered movement patterns in people with PFP. Some mobilization techniques have been designed to address joint misalignments. Objective: To investigate the acute effects of hip mobilization with movement (MWM) technique on pain and biomechanics during squats and jumps in females with and without PFP. Design: Randomized, placebo-controlled trial. Setting: Movement analysis laboratory. Patients: Fifty-six physically active females (28 with PFP and 28 asymptomatic) were divided into 4 groups: experimental group with PFP, sham group with PFP, experimental group without PFP, and sham group without PFP. Intervention(s): The experimental groups received MWM for the hip, and the sham groups received sham mobilization. Main Outcome Measures: Pain, trunk, and lower-limb kinematics, and hip and knee kinetics during single-leg squats and landings. Results: After the interventions, no difference between groups was found for pain. The PFP experimental group decreased hip internal rotation during squats compared with the PFP sham group (P = .03). There was no other significant difference between PFP groups for kinematic or kinetic outcomes during squats, as well as for any outcome during landings. There was no difference between asymptomatic groups for any of the outcomes in any of the tasks. Conclusions: Hip mobilization was ineffective to reduce pain in people with PFP. Hip MWM may contribute to dynamic lower-limb realignment in females with PFP by decreasing hip internal rotation during squats. Therefore, hip MWM could be potentially useful as a complementary intervention for patients with PFP.
Temporal Patterns of Knee-Extensor Isokinetic Torque Strength in Male and Female Athletes Following Comparison of Anterior Thigh and Knee Cooling Over a Rewarming Period
Authors: Alexander Jill , Rhodes David
Published: May 2019

Context: The effect of local cooling on muscle strength presents conflicting debates, with literature undecided as to the potential implications for injury, when returning to play following cryotherapy application. Objective: To investigate concentric muscle strength following local cooling over the anterior thigh compared with the knee joint in males and females and the temporal pattern over a 30-minute rewarming period. Design: Repeated-measures crossover design. Method: Twelve healthy participants randomly assigned to receive cooling intervention on one location, directly over either the anterior thigh or the knee, returning 1 week later to receive the cooling intervention on opposite location. Muscle strength measured via an isokinetic dynamometer at multiple time points (immediately post, 10-, 20-, and 30-min post) coincided with measurement of skin surface temperature (Tsk) using a noninvasive infrared camera. Results: Significant main effects for time (P ≤ .001, η2 = .126) with preice application higher than all other time points (P ≤ .05) were demonstrated for both peak torque and average torque. There were also significant main effects for isokinetic testing speed, sex of the participant, and position of the ice application for both peak torque and average torque (P ≤ .05). Statistically significant decreases in Tsk were reported in both gender groups across all time points compared with preintervention Tsk for the anterior thigh and knee (P < .05). Conclusions: Reductions reported for concentric peak torque and average torque knee-extensor strength in males and females did not fully recover to baseline measures at 30-minute postcryotherapy interventions. Sports medicine practitioners should consider strength deficits of the quadriceps after wetted ice applications, regardless of cooling location (joint/muscle) or gender.
Lack of Consensus on Return-to-Sport Criteria Following Lateral Ankle Sprain: A Systematic Review of Expert Opinions
Authors: Wikstrom Erik A. , Mueller Cole , Cain Mary Spencer
Published: May 2019

Context:Lateral ankle sprains (LAS) have one of the highest recurrence rates of all musculoskeletal injuries. An emphasis on rapid return to sport (RTS) following LAS likely increases reinjury risk. Unfortunately, no set of objective RTS criteria exist for LAS, forcing practitioners to rely on their own opinion of when a patient is ready to RTS.Purpose:To determine if there was consensus among published expert opinions that could help inform an initial set of RTS criteria for LAS that could be investigated in future research.Evidence Acquisition:PubMed, CINHL, and SPORTDiscus databases were searched from inception until October 2018 using a combination of keywords. Studies were included if they listed specific RTS criteria for LAS. No assessment of methodological quality was conducted because all included papers were expert opinion papers (level 5 evidence). Extracted data included the recommended domains (eg, range of motion, balance, sport-specific movement, etc) to be assessed, specific assessments for each listed domain, and thresholds (eg, 80% of the uninjured limb) to be used to determine RTS. Consensus and partial agreement were defined, a priori, as ≥75% and 50% to 75% agreement, respectively.Evidence Synthesis:Eight domains were identified within 11 included studies. Consensus was reached regarding the need to assess sport-specific movement (n = 9, 90.9%). Partial agreement was reached for the need to assess static balance (n = 7, 63.6%). The domains of pain and swelling, patient reported outcomes, range of motion, and strength were also partially agreed on (n = 6, 54.5%). No agreement was reached on specific assessments of cutoff thresholds.Conclusions:Given consensus and partial agreement results, RTS decisions following LAS should be based on sport-specific movement, static balance, patient reported outcomes, range of motion, and strength. Future research needs to determine assessments and cutoff thresholds within these domains to minimize recurrent LAS risk.
Early Morning Training Impacts Previous Night’s Sleep in NCAA Division I Cross Country Runners
Authors: Benjamin Courteney L. , Adams William M. , Curtis Ryan M. , Sekiguchi Yasuki , Giersch Gabrielle E.W. , Casa Douglas J.
Published: May 2019

The effects of training time on sleep has been previously studied; however, the influence on sleep in female collegiate cross-country runners is unknown. The aim of this study was to investigate the influence of training time on self-reported sleep metrics. Eleven female collegiate cross-country runners (mean [M] age = 19 years, standard deviation [SD] age = 1 year; M [SD] body mass = 58.8 [9.6] kg; M [SD] height = 168.4 [7.7] cm; M [SD] VO2max = 53.6 [5.6] mL·kg−1·min−1) competing in the 2016 NCAA cross-country season were included in this study. Participants completed a sleep diary daily to assess perceived measures of sleep on days when training took place between the hours of 5:00–8:00 a.m. (AM), and when training did not take place during this time (NAM). Sleep quality questions utilized a 5-point Likert scale, in which a score of 1 is associated with the worst outcomes and a score of 5 is associated with the best outcomes. Sleep duration was significantly higher on NAM (M [SD] = 8.26 [1.43] h) compared to AM (M [SD] = 7.97 [1.09] h, p < .001). Sleep quality was significantly higher on NAM (M [SD] = 3.30 [1.01]) compared to AM (M [SD] = 3.02 [1.06], p < .001). The impairment of sleep quantity and quality the night prior to early morning training suggests that future considerations should be made to sleep schedules and/or training times to optimize perceived sleep quality.
Melting of sediments in the deep mantle produces saline fluid inclusions in diamonds
Authors: Förster Michael W. , Foley Stephen F. , Marschall Horst R. , Alard Olivier , Buhre Stephan
Published: May 2019

We demonstrate the formation of highly saline mantle fluids by the reaction of subducted sediment with peridotite.
Worldwide phylogeography and history of wheat genetic diversity
Authors: Balfourier François , Bouchet Sophie , Robert Sandra , De Oliveira Romain , Rimbert Hélène , Kitt Jonathan , Choulet Frédéric ,   International Wheat Genome Sequencing Consortium,   BreedWheat Consortium, Paux Etienne
Published: May 2019

A phylogeographical study reveals the reshuffling of wheat genetic diversity through time, in relation to human history.
Predominance of Anaerobic, Spore-Forming Bacteria in Metabolically Active Microbial Communities from Ancient Siberian Permafrost
Authors: Liang Renxing , Lau Maggie , Vishnivetskaya Tatiana , Lloyd Karen G. , Wang Wei , Wiggins Jessica , Miller Jennifer , Pfiffner Susan , Rivkina Elizaveta M. , Onstott Tullis C.
Published: May 2019

Understanding the long-term survivability and associated metabolic traits of microorganisms in ancient permafrost frozen millions of years ago provides a unique window into the burial and preservation processes experienced in general by subsurface microorganisms in sedimentary deposits because of permafrost’s hydrological isolation and exceptional DNA preservation. We employed aspartic acid racemization modeling and metagenomics to determine which microbial communities were metabolically active in the 1.1-Ma permafrost from northeastern Siberia. The simultaneous sequencing of extracellular and intracellular genomic DNA provided insight into the metabolic potential distinguishing extinct from extant microorganisms under frozen conditions over this time interval. This in-depth metagenomic sequencing advances our understanding of the microbial diversity and metabolic functions of extant microbiomes from early Pleistocene permafrost. Therefore, these findings extend our knowledge of the survivability of microbes in permafrost from 33,000 years to 1.1 Ma.
Two Different Quinohemoprotein Amine Dehydrogenases Initiate Anaerobic Degradation of Aromatic Amines in Aromatoleum aromaticum EbN1
Authors: Schmitt Georg , Saft Martin , Arndt Fabian , Kahnt Jörg , Heider Johann
Published: May 2019

The known substrate spectrum of
A. aromaticum
EbN1 is expanded toward aromatic amines, which are metabolized as sole substrates coupled to denitrification. The characterization of the two quinohemoprotein isoenzymes involved in degrading either 2-PEA or BAm expands the knowledge of this enzyme family and establishes for the first time that the necessary maturation of their quinoid CTQ cofactors does not require the presence of molecular oxygen. Moreover, the study revealed a highly interesting regulatory phenomenon, suggesting that growth with BAm leads to a complete replacement of 2-PEADH by BAmDH, which has considerably different catalytic and inhibition properties.
A CRISPR Activation Screen Identifies Genes That Protect against Zika Virus Infection
Authors: Dukhovny Anna , Lamkiewicz Kevin , Chen Qian , Fricke Markus , Jabrane-Ferrat Nabila , Marz Manja , Jung Jae U. , Sklan Ella H.
Published: May 2019

Zika virus (ZIKV) is an emerging vector-borne pathogen causing a febrile disease. ZIKV infection might also trigger Guillain-Barré syndrome, neuropathy, and myelitis. Vertical transmission of ZIKV can cause fetus demise, stillbirth, or severe congenital abnormalities and neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We used a genome-wide CRISPR activation screen, where genes are activated from their native promoters to identify host cell factors that protect cells from ZIKV infection or associated cell death. The results provide a better understanding of key host factors that protect cells from ZIKV infection and might assist in identifying novel antiviral targets.
Draft Genome Sequence of Plant Growth-Promoting Endophytic
Microbacterium hydrothermale
BPSAC84, Isolated from the Medicinal Plant
Mirabilis jalapa
Authors: Passari Ajit Kumar , Rajput Vinay , Zothanpuia  , Priya Lakshmi P. M. , Dharne Mahesh , Dastager Syed , Mathew Oommen K. , Hashem Abeer , Abd_ Allah Elsayed Fathi , Singh Bhim Pratap
Published: May 2019

Endophytic
Microbacterium hydrothermale
strain BPSAC84, which has antimicrobial potential, was isolated from root tissues of
Mirabilis jalapa
in Mizoram, Northeast India. The draft genome consists of 3.58 Mb and 3,444 protein-coding sequences.
Royal College of Ophthalmologists’ National Ophthalmology Database study of cataract surgery: report 6. The impact of EyeSi virtual reality training on complications rates of cataract surgery performed by first and second year trainees
Authors: Ferris John D , Donachie Paul H , Johnston Robert L , Barnes Beth , Olaitan Martina , Sparrow John M
Published: May 2019

Objective

To investigate the impact of EyeSi surgical simulators on posterior capsule rupture (PCR) rates of cataract surgery performed by first and second year trainee surgeons.

Design

A Royal College of Ophthalmologists’ National Ophthalmology Database audit study of first and second year surgeons’ PCR rates over seven consecutive National Health Service (NHS) years. Participating centres were contacted to ascertain the date when their surgeons had access to an EyeSi machine and whether this was on-site or off-site. Operations were classified as before, after or no access to EyeSi.

Setting

The study took place in 29 NHS Ophthalmology Units in a secondary care setting.

Results

Two-hundred and sixty five first and second year trainee surgeons performed 17 831 cataract operations. 6919 (38.8%) operations were performed before access to an EyeSi, 8648 (48.5%) after access to an EyeSi and 2264 (12.7%) operations by surgeons with no access to an EyeSi. Overall, there was a 38% reduction in the first and second year surgeon’s unadjusted PCR rates from 4.2% in 2009 to 2.6% in 2015 for surgeons with access to an EyeSi, and a 3% reduction from 2.9% to 2.8% for surgeons without access to an EyeSi. The overall first and second year unadjusted PCR rates for before, after and no access to EyeSi were 3.5%, 2.6% and 3.8%, respectively. The decrease in the with-access to an EyeSi group PCR rate was similar for surgeons with access to an EyeSi ‘on site’ or ‘off site’.

Conclusions

First and second year trainee surgeons’ unadjusted PCR rates have decreased since 2009 which has significant benefits for patients undergoing cataract surgery. This 38% reduction in complication rates aligns with the introduction of EyeSi simulator training.
Optical coherence tomography angiography of perilimbal vasculature: validation of a standardised imaging algorithm
Authors: Patel Chaitali N , Antony Anjaly K , Kommula Hasna , Shah Sahil , Singh Vivek , Basu Sayan
Published: May 2019

Purpose

To test the reliability and accuracy of a standardised non-invasive imaging algorithm using optical coherence tomography angiography (OCTA) in detecting and quantifying pharmacologically induced changes in the perilimbal vasculature.

Methods

In this prospective observational imaging study, 370 angiograms of 15 normal eyes and 10 eyes with nasal pterygiums were obtained using a commercially available OCTA system with split-spectrum amplitude-decorrelation angiography technology. Postprocessing of the images to quantify the area occupied by the blood vessels was performed using the Fiji software. The main outcome measures were reliability (intraobserver and interobserver agreement) and accuracy of the standardised algorithm in detecting and quantifying relative change (vasoconstriction and vasodilatation) in the area occupied by the blood vessels after instillation of topical vasoconstrictors.

Results

The intraclass correlation coefficients for intraobserver and interobserver agreement were 0.91 and 0.88 (good to excellent), respectively. In normal eyes, significant vasoconstriction was noted at 5 min (35%–47%) after application of eye-drops, which peaked at 10 min (43%–63%) and was sustained until 20 min (35%–51%), followed by gradual recovery. Greatest effect was noted with a combination of 5% phenylephrine and 0.15% brimonidine tartrate (BT) eye-drops as compared with either one or two drops of BT alone, both at the 10 min (p=0.0058) and 20 min (p=0.0375) time points. This dose-dependent temporal trend was replicated in eyes with primary nasal pterygium (p=0.31).

Conclusions

The findings suggest that OCTA can reliably and accurately detect and quantify relative changes in the perilimbal vasculature in both normal eyes and in eyes with pterygium.
Effect of dose of behavioral weight loss treatment on glycemic control in adults with prediabetes
Authors: Bauman Viviana , Ariel-Donges Aviva H , Gordon Eliza L , Daniels Michael J , Xu Dandan , Ross Kathryn M , Limacher Marian C , Perri Michael G
Published: May 2019

Objective

This study examined the effects of three doses of behavioral weight loss treatment, compared with a nutrition education control group, on changes in glycemic control in individuals with obesity and prediabetes.

Research design and methods

The study included 287 adults (77% female, 81% White; mean (SD) age=54.1 (10.5) years, body mass index=36.3 (3.9) kg/m2, and hemoglobin A1c (HbA1c)=5.9 (0.2%)). Participants were randomized to one of three behavioral treatment doses (high=24 sessions, moderate=16 sessions, or low=8 sessions) or to an education group (control=8 sessions). Changes in HbA1c, fasting glucose, and body weight were assessed from baseline to 6 months.

Results

Mean (99.2% credible interval (CI)) reductions in HbA1c were 0.11% (0.07% to 0.16%), 0.08% (0.03% to 0.13%), 0.03% (–0.01% to 0.07%), and 0.02% (–0.02% to 0.07%), for the high, moderate, low, and control conditions, respectively. Mean (CI) reductions in fasting blood glucose were 0.26 mmol/L (0.14 to 0.39), 0.09 mmol/L (0 to 0.19), 0.01 mmol/L (–0.07 to 0.09), and 0.04 mmol/L (–0.03 to 0.12) for the high, moderate, low, and control conditions, respectively. The high-dose treatment produced significantly greater reductions in HbA1c and fasting blood glucose than the low-dose and control conditions (posterior probabilities (pp)<0.001); no other significant between-group differences were observed. Mean (CI) reductions in body weight were 10.91 kg (9.30 to 12.64), 10.08 kg (8.38 to 11.72), 6.35 kg (5.19 to 7.69), and 3.82 kg (3.04 to 4.54) for the high, moderate, low, and control conditions, respectively. All between-group differences in 6-month weight change were significant (pps<0.001) except for the high-dose versus moderate-dose comparison.

Conclusion

For adults with obesity and prediabetes a high dose of behavioral treatment involving 24 sessions over 6 months may be needed to optimize improvements in glycemic control.

Trial registration number

NCT00912652.
Anti-vascular endothelial growth factor treatment for retinal conditions: a systematic review and meta-analysis
Authors: Pham Ba' , Thomas Sonia M , Lillie Erin , Lee Taehoon , Hamid Jemila , Richter Trevor , Janoudi Ghayath , Agarwal Arnav , Sharpe Jane P , Scott Alistair , Warren Rachel , Brahmbhatt Ronak , Macdonald Erin , Straus Sharon E , Tricco Andrea C
Published: May 2019

Objectives

To evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV).

Design

Systematic review and random-effects meta-analysis.

Methods

Multiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged ≥18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias.

Results

19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6–9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients.

Conclusions

Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (≥15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen.

PROSPERO registration number

CRD42015022041.
To what extent does sex, age and BMI impact medical and pharmacy costs? A retrospective cohort study involving employees in a large school district in the USA
Authors: Merrill Ray M , Fowers Rylan
Published: May 2019

Objective

To identify the extent that sex, age and body mass index (BMI) is associated with medical and pharmacy costs.

Design

Retrospective cohort.

Setting

A school district in the Western USA involving 2531 workers continuously employed during 2011–2014.

Main outcome measures

Medical and pharmacy costs and BMI.

Results

Approximately 84% of employees participated in wellness screening. Participants were 1.03 (95% CI 1.01 to 1.06) times more likely to be women and younger (M=47.8 vs 49.8, p<0.001). Median medical and pharmacy costs were higher for women than men, increased with age, and were greater in morbidly obese individuals (p<0.001). Annual pharmacy claims were 18% more likely to be filed by women than men, 23% more likely filed by those aged ≥60 versus <40 years, and 6% more likely filed by morbidly obese individuals than of normal weight (p<0.001) individuals. Greater medical and pharmacy costs in older age were most pronounced in underweight and morbidly obese groups. Higher use of medication among women than men was primarily because of drugs involving birth control, osteoporosis, thyroid disease and urinary tract infection. Higher medication use in older age was primarily related to medications used to treat gastrointestinal problems. Medication use was positively associated with BMI weight classifications for most of the 33 drug types considered, with exceptions involving birth control, herpes and osteoporosis. A J-shape relationship was observed between BMI and medication use for acne, antibiotic, cold/influenza/allergy, eye infection, oedema, muscle spasms, pain and ulcers.

Conclusions

Medications associated with higher medical and pharmacy costs among women, older age and underweight or obese individuals are identified. Lowering medical and pharmacy costs requires weight management in older ages, particularly for underweight and obese. Higher pharmacy costs for certain drugs among underweight individuals may be associated with poorer nutrition.
Five-year prognosis and impact of adolescent knee pain: a prospective population-based cohort study of 504 adolescents in Denmark
Authors: Rathleff Michael Skovdal , Holden Sinead , Straszek Christian Lund , Olesen Jens Lykkegaard , Jensen Martin Bach , Roos Ewa M
Published: May 2019

Objectives

Investigate the prognosis of adolescent knee pain, and evaluate its impact on health, care-seeking and career choices 5 years later.

Design

Pre-registered, prospective cohort study.

Setting

Population-based cohort initiated in school setting.

Participants

From a cohort of 2200 adolescents aged 15–19 years in 2011, 504 reported knee pain on at least a monthly basis, and were followed prospectively in this cohort study, together with 252 controls who did not have knee pain in 2011.

Main outcome measures

Outcomes included the Pain and Symptoms subscales from the Knee injury and Osteoarthritis Outcome Score (KOOS), pain intensity measured with a Numeric Rating Scale, pain frequency, knee-related and health-related quality of life, sports participation, physical activity level, KOOS subscales: Function and Sport/recreation, quality of sleep, healthcare consultations, treatments received for their knee pain, the use of painkillers and impact on choice of job or career.

Results

At follow-up, 358 (71.0%) from the knee pain group and 182 (72.2%) from the control group responded. Of note, 40.5% (95% CI: 35.4% to 45.6%) from the knee pain group reported knee pain 5 years later which was frequent and intense compared with 13.2% (95% CI: 8.2 to 18.1) of the control group. Those from the knee pain group still suffering from knee pain reported poorer physical health (13 points worse on KOOS Function and 30 points worse on KOOS Sport/recreation), stopped or reduced their sports participation because of knee pain (60%), reported worse sleep quality and worse knee-related and general quality of life. In terms of health behaviours, those still with knee pain reported more healthcare consultations. One-third used pain killers regularly, and 15% (95% CI: 12% to 20%) reported that knee pain influenced their choice of job or career.

Conclusion

Four out of every 10 adolescents with knee pain still experienced frequent and intense knee pain 5 years later, severe enough to impact health, health behaviours and career choices.

Trail registration number

NCT02873143.
Time-driven activity-based costing of total knee replacements in Karachi, Pakistan
Authors: Khan Rabia Mansoor , Albutt Katherine , Qureshi Muhammad Abdullah , Ansari Zara , Drevin Gustaf , Mukhopadhyay Swagoto , Khan Mansoor Ali , Chinoy Muhammad Amin , Meara John , Hussain Hamidah
Published: May 2019

Introduction

Osteoarthritis of the knee has been identified as the most common disability in Pakistan. Total knee replacement (TKR) surgery is the curative treatment for advanced osteoarthritis of the knee; however, cost remains one of the barriers to effective and timely service delivery.

Objective

We conducted a time-driven activity-based costing (TDABC) analysis of TKR to identify major cost drivers and areas for process improvement.

Methods and analysis

We performed a prospective TDABC analysis of patients who underwent bilateral TKR at The Indus Hospital (TIH) during a 14-month period from October 2015 to December 2016. Detailed process maps were developed for each phase of the care cycle. Time durations and costs were allocated to each resource utilised and aggregated across the care cycle, including personnel, direct and indirect costs.

Results

We identified seven care phases for a complete TKR care cycle and created their detailed process maps. Major time contributors were ward stay and discharge (20 160 min), TKR surgery (563 min) and surgical admission (333 min). Overall, 92.10% of time is spent during the ward stay and discharge phase of care. Patients remain hospitalised for an average of 14 days postoperatively. Overall institutional cost of a TKR at TIH was US$4360.51 (Pakistani rupees 456 981.17) per bilateral TKR surgery. The overall primary cost drivers for the full bundle of care were consumables used during TKR surgery itself, consumables utilised in the wards and personnel costs contributing 57.64%, 27.45% and 12.03% of total costs, respectively.

Conclusion

Utilising TDABC allowed us to obtain a granular analysis of time and cost that was subsequently used to inform quality process improvement initiatives. In low-resource settings, such as Pakistan, TDABC has the potential to be a useful tool to guide resource allocation and process improvement.
Measuring financial risk protection in health benefits packages: scoping review protocol to inform allocative efficiency studies
Authors: Abou Jaoude Gerard Joseph , Skordis-Worrall Jolene , Haghparast-Bidgoli Hassan
Published: May 2019

Introduction

To progress towards Universal Health Coverage (UHC), countries will need to define a health benefits package of services free at the point of use. Financial risk protection is a core component of UHC and should therefore be considered a key dimension of health benefits packages. Allocative efficiency modelling tools can support national analytical capacity to inform an evidence-based selection of services, but none are currently able to estimate financial risk protection. A review of existing methods used to measure financial risk protection can facilitate their inclusion in modelling tools so that the latter can become more relevant to national decision making in light of UHC.

Methods and analysis

This protocol proposes to conduct a scoping review of existing methods used to measure financial risk protection and assess their potential to inform the selection of services in a health benefits package. The proposed review will follow the methodological framework developed by Arksey and O’Malley and the subsequent recommendations made by Levacet al. Several databases will be systematically searched including: (1) PubMed; (2) Scopus; (3) Web of Science and (4) Google Scholar. Grey literature will also be scanned, and the bibliography of all selected studies will be hand searched. Following the selection of studies according to defined inclusion and exclusion criteria, key characteristics will be collected from the studies using a data extraction tool. Key characteristics will include the type of method used, geographical region of focus and application to specific services or packages. The extracted data will then be charted, collated, reported and summarised using descriptive statistics, a thematic analysis and graphical presentations.

Ethics and dissemination

The scoping review proposed in this protocol does not require ethical approval. The final results will be disseminated via publication in a peer-reviewed journal, conference presentations and shared with key stakeholders.
General practitioner use of D-dimer in suspected venous thromboembolism: historical cohort study in one geographical region in the Netherlands
Authors: Schols Angel M R , Meijs Eline , Dinant Geert-Jan , Stoffers Henri E J H , Krekels Mariëlle M E , Cals Jochen W L
Published: May 2019

Objectives

To investigate how many general practitioner (GP)-referred venous thromboembolic events (VTEs) are diagnosed during 1 year in one geographical region and to investigate the (urgent) referral pathway of VTE diagnoses, including the role of laboratory D-dimer testing.

Design

Historical cohort study.

Setting

GP patients of 47 general practices in a demarcated geographical region of 161 503 inhabitants in the Netherlands.

Participants

We analysed all 895 primary care patients in whom either the GP determined a D-dimer value or who had a diagnostic work-up for suspected VTE in a non-academic hospital during 2015.

Primary and secondary outcome measures

The primary outcomes of this study were the total number of VTEs per year and the diagnostic pathways—including the role of GP determined D-dimer testing—of patients urgently referred to secondary care for suspected VTE. Additionally, we explored the use of an age-adjusted D-dimer cut-off.

Results

The annual VTE incidence was 0.9 per 1000 inhabitants. GPs annually ordered 5.1 D-dimer tests per 1000 inhabitants. Of 470 urgently GP-referred patients, 31.3% had a VTE. Of those urgently referred based on clinical assessment only (without D-dimer testing), 73.8% (96/130) had a VTE; based on clinical assessment and laboratory D-dimer testing yielded 15.0% (51/340) VTE. Applying age-adjusted D-dimer cut-offs to all patients aged 50 years or older resulted in a reduction of positive D-dimer results from 97.9% to 79.4%, without missing any VTE.

Conclusions

Although D-dimer testing contributes to the diagnostic work-up of VTE, GPs have a high detection rate for VTE in patients who they urgently refer to secondary care based on clinical assessment only.
Identification of Plasmodium falciparum and host factors associated with cerebral malaria: description of the protocol for a prospective, case-control study in Benin (NeuroCM)
Authors: Joste Valentin , Maurice Laurine , Bertin Gwladys I , Aubouy Agnès , Boumédiène Farid , Houzé Sandrine , Ajzenberg Daniel , Argy Nicolas , Massougbodji Achille , Dossou-Dagba Ida , Alao Maroufou Jules , Cot Michel , Deloron Philippe , Faucher Jean-François
Published: May 2019

Introduction

In 2016, an estimated 216 million cases and 445 000 deaths of malaria occurred worldwide, in 91 countries. In Benin, malaria causes 26.8% of consultation and hospitalisation motif in the general population and 20.9% in children under 5 years old.

The goal of the NeuroCM project is to identify the causative factors of neuroinflammation in the context of cerebral malaria. There are currently very few systematic data from West Africa on the aetiologies and management of non-malarial non-traumatic coma in small children, and NeuroCM will help to fill this gap. We postulate that an accurate understanding of molecular and cellular mechanisms involved in neuroinflammation may help to define efficient strategies to prevent and manage cerebral malaria.

Methods and analysis

This is a prospective, case-control study comparing cerebral malaria to uncomplicated malaria and non-malarial non-traumatic coma. This study takes place in Benin, precisely in Cotonou for children with coma and in Sô-Ava district for children with uncomplicated malaria. We aim to include 300 children aged between 24 and 71 months and divided in three different clinical groups during 12 months (from December 2017 to November 2018) with a 21 to 28 days follow-up for coma. Study data, including clinical, biological and research results will be collected and managed using CSOnline-Ennov Clinical.

Ethics and dissemination

Ethics approval for the NeuroCM study has been obtained fromComité National d’Ethique pour la Recherche en santéof Benin (n°67/MS/DC/SGM/DRFMT/CNERS/SA; 10/17/2017). NeuroCM study has also been approved byComité consultatif de déontologie et d’éthiqueof Institut de Recherche pour le Développement (IRD; 10/24/2017). The study results will be disseminated through the direct consultations with the WHO’s Multilateral Initiative on Malaria (TDR-MIM) and Roll Back Malaria programme, through scientific meetings and peer-reviewed publications in scientific or medical journals, and through guidelines and booklets.