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Time-elapsed synchrotron-light microstructural imaging of femoral neck fracture
Get PDFThis is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).Time-elapsed micro-computed-tomography (μCT) imaging allows studying bone micromechanics. However, no study has yet performed time-elapsed μCT imaging of human femoral neck fractures. We developed a protocol for time-elapsed synchrotron μCT imaging of the microstructure in the entire proximal femur, while inducing clinically-relevant femoral neck fractures. Three human cadaver femora (females, age: 75–80 years) were used. The specimen-specific force to be applied at each load step was based on the specimens’ strength estimated a priori using finite-element analysis of clinical CT images. A radio-transparent compressive stage was designed for loading the specimens while recording the applied load during synchrotron μCT scanning. The total μCT scanning field of view was 146 mm wide and 131 mm high, at 29.81 µm isotropic pixel size. Specimens were first scanned unloaded, then under incremental load steps, each equal to 25% of the estimated specimens’ strength, and ultimately after fracture. Fracture occurred after 4–5 time-elapsed load steps, displaying sub-capital fracturing of the femoral neck, in agreement with finite-element predictions. Time-elapsed μCT images, co-registered to those of the intact specimen, displayed the proximal femur microstructure under progressive deformation up to fracture. The images showed (1) a spatially heterogeneous deformation localized in the proximal femoral head; (2) a predominantly elastic recovery, after load removal, of the diaphyseal and trochanteric regions and; (3) post-fracture residual displacements, mainly localized in the fractured region. The time-elapsed μCT imaging protocol developed and the high resolution images generated, made publicly available, may spur further research into human femur micromechanics and fracture.This work was supported by the Australian Research Council [DE140101530] and by the Australian Synchrotron (Clayton, VIC, Australia)
Sex differences in macronutrient intake and adherence to dietary recommendations: findings from the UK Biobank
Get PDFNo commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Objectives To characterise sex differences in macronutrient intakes and adherence to dietary recommendations in the UK Biobank population.
Design Cross-sectional population-based study.
Setting UK Biobank Resource.
Participants 210 106 (52.5% women) individuals with data on dietary behaviour.
Main outcome measures Women-to-men mean differences in nutrient intake in grams and as a percentage of energy and women-to-men ORs in non-adherence, adjusting for age, socioeconomic status and ethnicity.
Results There were sex differences in energy intake and distribution. Men had greater intakes of energy and were less likely to have energy intakes above the estimated average requirement compared with women. Small, but significant, sex differences were found in the intakes of all macronutrients. For all macronutrients, men had greater absolute intakes while women had greater intakes as a percentage of energy. Women were more likely to have intakes that exceeded recommendations for total fat, saturated fat and total sugar. Men were less likely to achieve the minimum recommended intakes for protein, polyunsaturated fat and total carbohydrate. Over 95% of men and women were non-adherent to fibre recommendations. Sex differences in dietary intakes were moderated by age and to some extent by socioeconomic status.
Conclusions There are significant sex differences in adherence to dietary recommendations, particularly for sugar. However, given the increased focus on food groups and dietary patterns for nutritional policy, these differences alone may not be sufficient for policy and health promotion. Future studies that are able to explore the sex differences in intakes of different food groups that are risk factors for diet-related diseases are warranted to improve the current understanding of the differential impact of diet on health in women and men.SAEP is supported by a UK Medical Research Council Skills Development
Fellowship (MR/P014550/1). MW is supported by an Australian National Health and
Medical Council Principal Research Fellowship
Treatment of scabies using a tea tree oilbased gel formulation in Australian Aboriginal children: protocol for a randomised controlled trial
Get PDFNo commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Introduction In remote Aboriginal communities in Australia, scabies affects 7 out of 10 children before their first birthday. This is more than six times the rate seen in the rest of the developed world. Scabies infestation is frequently complicated by bacterial infection, leading to the development of skin sores and other more serious consequences, such as septicaemia and chronic heart and kidney diseases. Tea tree oil (TTO) has been used as an antimicrobial agent for several decades with proven clinical efficacy. Preclinical investigations have demonstrated superior scabicidal properties of TTO compared with widely used scabicidal agents, such as permethrin 5% cream and ivermectin. However, current data are insufficient to warrant a broad recommendation for its use for the management of scabies because previous studies were small or limited to in vitro observations.
Methods and analysis A pragmatic first trial will examine the clinical efficacy of a simple and low-cost TTO treatment against paediatric scabies and the prevention of associated secondary bacterial infections, with 1:1 randomisation of 200 participants (Aboriginal children, aged 5–16 years and living in remote Australia) into active control (permethrin 5% cream) and treatment (5% TTO gel) groups. The primary outcome for the study is clinical cure (complete resolution). Secondary outcome measures will include relief of symptoms, recurrence rate, adverse effects, adherence to treatment regimen and patient acceptability.This work was supported by a grant received from University of Canberra
Collaborative Indigenous Research Initiative (2016-2018)
Standardising evidence strength grading for recommendations from multiple clinical practice guidelines: a South African case study
Get PDFOpen Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background
Significant resources are required to write de novo clinical practice guidelines (CPGs). There are many freely-available CPGs internationally, for many health conditions. Developing countries rarely have the resources for de novo CPGs, and there could be efficiencies in using CPGs developed elsewhere. This paper outlines a novel process developed and tested in a resource-constrained country (South Africa) to synthesise findings from multiple international CPGs on allied health (AH) stroke rehabilitation.
Methods
Methodologists, policy-makers, content experts and consumers collaborated to describe the pathway of an ‘average’ stroke patient through the South African public healthcare system and pose questions about best-practice stroke rehabilitation along this pathway. A comprehensive search identified international guidance documents published since January 2010. These were scanned for relevance to the South African AH stroke rehabilitation questions and critically appraised for methodological quality. Recommendations were extracted from guidance documents for each question. Strength of the body of evidence (SoBE) gradings underpinning recommendations were standardised, and composite recommendations were developed using qualitative synthesis. An algorithm was developed to guide assignment of overall SoBE gradings to composite recommendations.
Results
Sixteen CPGs were identified, and all were included, as they answered different project questions differently. Methodological quality varied and was unrelated to currency. Seven clusters, outlining 20 composite recommendations were proposed (organise for best practice rehabilitation, operationalise strategies for best practice communication throughout the patient journey, admit to an acute hospital, refer to inpatient rehabilitation, action inpatient rehabilitation, discharge from inpatient rehabilitation and longer-term community-based rehabilitation).
Conclusion
The methodological development process, tested by writing a South African AH stroke rehabilitation guideline from existing evidence sources, took 9 months. The process was efficient, collaborative, effective, rewarding and positive. Using the proposed methods, similar synthesis of existing evidence could be conducted in shorter time periods, in other resource-constrained countries, avoiding the need for expensive and time-consuming de novo CPG development
A Systematic Review and Meta-Analysis of Human Milk Feeding and Morbidity in Very Low Birth Weight Infants
Get PDFThis article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and neurodevelopment in infants born ≤28 weeks’ gestation and/or publications with reported infant mean birth weight of ≤1500 g. Online databases including Medline, PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials were searched, and comparisons were grouped as follows: exclusive human milk (EHM) versus exclusive preterm formula (EPTF), any human milk (HM) versus EPTF, higher versus lower dose HM, and unpasteurised versus pasteurised HM. Experimental and observational studies were pooled separately in meta-analyses. Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings. Forty-nine studies (with 56 reports) were included, of which 44 could be included in meta-analyses. HM provided a clear protective effect against NEC, with an approximate 4% reduction in incidence. HM also provided a possible reduction in LOS, severe ROP and severe NEC. Particularly for NEC, any volume of HM is better than EPTF, and the higher the dose the greater the protection. Evidence regarding pasteurisation is inconclusive, but it appears to have no effect on some outcomes. Improving the intake of mother’s own milk (MOM) and/or donor HM results in small improvements in morbidity in this population.This research received no external funding. Collins’ salary was supported by a Research Fellowship
from the M.S. McLeod Research Fund of the Women’s and Children’s Hospital Research Foundation and NHMRC
TRIP Fellowship 1132596. Outside the submitted work, M.M. serves on scientific advisory boards for Fonterra and
Nestle. Honoraria are paid to her institution for continuing education of early career researchers. M.M. also holds
a Principal Research Fellowship from the NHMRC (APP1061704). All other authors declare no conflict of interest
Therapist-Assisted Internet-Based Cognitive Behavioral Therapy Versus Progressive Relaxation in Obsessive-Compulsive Disorder: Randomized Controlled Trial
Get PDFOriginally published in the Journal of Medical Internet Research (http://www.jmir.org), 08.08.2018.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on http://www.jmir.org/, as well as this copyright and license information must be included.Background: Obsessive-compulsive disorder (OCD) is a highly disabling psychological disorder with a chronic course if left untreated. Cognitive behavioral therapy (CBT) has been shown to be an effective treatment, but access to face-to-face CBT is not always possible. Internet-based CBT (iCBT) has become an increasingly viable option. However, no study has compared iCBT to an analogous control condition using a randomized controlled trial (RCT).
Objective: A 2-armed RCT was used to compare a therapist-assisted 12-module iCBT to an analogous active attention control condition (therapist-assisted internet-based standard progressive relaxation training, iPRT) in adult OCD. This paper reports pre-post findings for OCD symptom severity.
Method: In total, 179 participants (117 females, 65.7%) were randomized (stratified by gender) into iCBT or iPRT. The iCBT intervention included psychoeducation, mood and behavioral management, exposure and response prevention (ERP), cognitive therapy, and relapse prevention; the iPRT intervention included psychoeducation and relaxation techniques as a way of managing OCD-related anxiety but did not incorporate ERP or other CBT elements. Both treatments included audiovisual content, case stories, demonstrations of techniques, downloadable audio content and worksheets, and expert commentary. All participants received 1 weekly email, with a maximum 15-minute preparation time per client from a remote therapist trained in e-therapy. Emails aimed to monitor progress, provide support and encouragement, and assist in individualizing the treatment. Participants were assessed for baseline and posttreatment OCD severity with the telephone-administered clinician-rated Yale-Brown Obsessive-Compulsive Scale and other measures by assessors who were blinded to treatment allocation.
Results: No pretreatment differences were found between the 2 conditions. Intention-to-treat analysis revealed significant pre-post improvements in OCD symptom severity for both conditions (P<.001). However, relative to iPRT, iCBT showed significantly greater symptom severity improvement (P=.001); Cohen d for iCBT was 1.05 (95% CI 0.72-1.37), whereas for iPRT it was 0.48 (95% CI 0.22-0.73). The iCBT condition was superior in regard to reliable improvement (25/51, 49% vs 16/55, 29%; P=.04) and clinically significant pre-post-treatment changes (17/51, 33% vs 6/55, 11%; P=.005). Those undertaking iCBT post completion of iPRT showed further significant symptom amelioration (P<.001), although the sequential treatment was no more efficacious than iCBT alone (P=.63).
Conclusion: This study is the first to compare a therapist-assisted iCBT program for OCD to an analogous active attention control condition using iPRT. Our findings demonstrate the large magnitude effect of iCBT for OCD; interestingly, iPRT was also moderately efficacious, albeit significantly less so than the iCBT intervention. The findings are compared to previous internet-based and face-to-face CBT treatment programs for OCD. Future directions for technology-enhanced programs for the treatment of OCD are outlined.This research was supported by a National Health and Medical Research Council (NHMRC) project grant (620506)
In silico (computed) modelling of doses and dosing regimens associated with morphine levels above international legal driving limits
Get PDFThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: Morphine can cause central nervous system side effects which impair driving skills. The legal blood morphine
concentration limit for driving is 20 μg/L in France/Poland/Netherlands and 80 μg/L in England/Wales. There is no guidance as to the
morphine dose leading to this concentration.
Aim: The in silico (computed) relationship of oral morphine dose and plasma concentration was modelled to provide dose estimates
for a morphine plasma concentration above 20 and 80 μg/L in different patient groups.
Design: A dose–concentration model for different genders, ages and oral morphine formulations, validated against clinical
pharmacokinetic data, was generated using Simcyp®, a population-based pharmacokinetic simulator.
Setting/participants: Healthy Northern European population parameters were used with age, gender and renal function being
varied in the different simulation groups. In total, 36,000 simulated human subjects (100 per modelled group of different ages and
gender) received repeated simulated morphine dosing with modified-release or immediate-release formulations.
Results: Older age, women, modified-release formulation and worse renal function were associated with higher plasma concentrations.
Across all groups, morphine doses below 20 mg/day were unlikely to result in a morphine plasma concentration above 20 μg/L; this
was 80 mg/day with the 80 μg/L limit.
Conclusion: This novel study provides predictions of the in silico (computed) dose–concentration relationship for international
application. Individualised morphine prescribing decisions by clinicians must be informed by clinical judgement considering the individual
patient’s level of impairment and insight irrespective of the blood morphine concentration as people who have impaired driving will be
breaking the law. Taking into account expected morphine concentrations enables improved individualised decision making.The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article:
D.F. is funded by Fundação para a Ciência e Tecnologia (FCT)
from the Portuguese Government (PhD grant SFRH/
BD/109920/2015)
Methylation and Gene Expression of BCAT1 and IKZF1 in Colorectal Cancer Tissues
Get PDFThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The genes BCAT1 and IKZF1 are hypermethylated in colorectal cancer (CRC), but little is known about how this relates to gene
expression. This study assessed the relationship between methylation and gene expression of BCAT1 and IKZF1 in CRC and adjacent non-neoplastic
tissues. The tissues were obtained at surgery from 36 patients diagnosed with different stages of CRC (stage I n = 8, stage II n = 13,
stage III n = 10, stage IV n = 5). Methylated BCAT1 and IKZF1 were detected in 92% and 72% CRC tissues, respectively, with levels independent
of stage (P > .05). In contrast, only 31% and 3% of non-neoplastic tissues were methylated for BCAT1 and IKZF1, respectively (P < .001). The
IKZF1 messenger RNA (mRNA) expression was significantly lower in the cancer tissues compared with that of non-neoplastic tissues, whereas
the BCAT1 mRNA levels were similar. The latter may be due to the BCAT1 polymerase chain reaction assay detecting more than 1 mRNA
transcript. Further studies are warranted to establish the role of the epigenetic silencing of IKZF1 in colorectal oncogenesis.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded in part by the National Health and Medical Research Council (APP1006242, APP1017083)
Inducing preference reversals in aesthetic choices for paintings: Introducing the contrast paradigm
Get PDFThis is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.Understanding what leads people to reverse their choices is important in many domains.
We introduce a contrast paradigm for studying reversals in choices - here between pairs of
abstract paintings - implemented in both within-subject (Experiment 1; N = 320) and between-
subject (Experiment 2; N = 384) designs. On each trial, participants chose between a
pair of paintings. A critical pair of average-beauty paintings was presented before and after
either a reversal or control block. In the reversal block, we made efforts to bias preference
away from the chosen average-beauty painting (by pairing it with more-beautiful paintings)
and toward the non-chosen average-beauty painting (by pairing it with less-beautiful paintings).
Meta-analysis revealed more reversals after reversal blocks than after control blocks,
though only when the biasing manipulations succeeded. A second meta-analysis revealed
that reversals were generally more likely for participants who later misidentified their initial
choice, demonstrating that memory for initial choices influences later choices. Thus, the
contrast paradigm has utility both for inducing choice reversals and identifying their causes.This research was supported by the
Natural Sciences and Engineering Research
Council of Canada through Discovery Grant RGPIN
238599-2015 to GEB
Religio-cultural factors contributing to perinatal mortality and morbidity in mountain villages of Nepal: Implications for future healthcare provision
Get PDFThis is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.Objective and the context
This paper examines the beliefs and experiences of women and their families in remote mountain villages of Nepal about perinatal sickness and death and considers the implications of these beliefs for future healthcare provision.
Methods
Two mountain villages were chosen for this qualitative study to provide diversity of context within a highly disadvantaged region. Individual in-depth interviews were conducted with 42 women of childbearing age and their family members, 15 health service providers, and 5 stakeholders. The data were analysed using a thematic analysis technique with a comprehensive coding process.
Findings
Three key themes emerged from the study: (1) ‘Everyone has gone through it’: perinatal death as a natural occurrence; (2) Dewata (God) as a factor in health and sickness: a cause and means to overcome sickness in mother and baby; and (3) Karma (Past deeds), Bhagya (Fate) or Lekhanta (Destiny): ways of rationalising perinatal deaths.
Conclusion
Religio-cultural interpretations underlie a fatalistic view among villagers in Nepal’s mountain communities about any possibility of preventing perinatal deaths. This perpetuates a silence around the issue, and results in severe under-reporting of ongoing high perinatal death rates and almost no reporting of stillbirths. The study identified a strong belief in religio-cultural determinants of perinatal death, which demonstrates that medical interventions alone are not sufficient to prevent these deaths and that broader social determinants which are highly significant in local life must be considered in policy making and programming.The principal author, MP, received
financial support (research students' maintenance
and postgraduate scholarship) from Flinders
University to carry out the fieldwork for this study