Search

In this contribution, we present an innovative data-driven model to reconstruct a reliable temporal pattern for time-lagged statistical monetary figures. Our research cuts across several domains regarding the production of robust economic inferences and the bridging of top-down aggregated information from central databases with disaggregated information obtained from local sources or national statistical offices. Our test bed case study is the European Regional Development Fund (ERDF). The application we discuss deals with the reported time lag between the local expenditures of ERDF by beneficiaries in Italian regions and the corresponding payments reported in the European Commission database. Our model reconstructs the timing of these local expenditures by back-dating the observed European Commission reimbursements. The inferred estimates are then validated against the expenditures reported from the Italian National Managing Authorities (NMAs) in terms of cumulative monetary difference. The lower cumulative yearly distance of our modelled expenditures compared to the official European Commission payments confirms the robustness of our model. Using sensitivity analysis, we also analyse the relative importance of the modelling parameters on the cumulative distance between the modelled and reported expenditures. The parameters with the greatest influence on the uncertainty of this distance are the following: first, how the non-clearly regionalised expenditures are attributed to individual regions; and second, the number of backward years that the residuals of the yearly payments are spread onto. In general, the distance between the modelled and reported expenditures can be further reduced by fixing these parameters. However, the gain is only marginal for some regions. The present study paves the way for modelling exercises that are aimed at more reliable estimates of the expenditures on the ground by the ultimate beneficiaries of European funds. Additionally, the output databases can contribute to enhancing the reliability of econometric studies on the effectiveness of European Union (EU) funds.

AimInvestigate the cost and effects of a single-pill versus two- or three pill first-line antiretroviral combinations in reducing viral load, increasing CD4 counts, and first-line failure rate associated with respective regimens at 6 and 12 months.MethodsPatients on first-line TDF+3TC+EFV, TDF+FTC+EFV, Truvada®+EFV or Atripla® between 1996-2008 were identified and viral load and CD4 counts measured at baseline, six and twelve months respectively. Factors that independently predicted treatment failure at six and twelve months were derived using multivariate Cox's proportional hazard regression analyses. Use and cost of hospital services were calculated at six and twelve months respectively.ResultsAll regimens reduced viral load to below the limit of detection and CD4 counts increased to similar levels at six and twelve months for all treatment regimens. No statistically significant differences were observed for rate of treatment failure at six and twelve months. People on Atripla® generated lower healthcare costs for non-AIDS patients at £5,340 (£5,254 to £5,426) per patient-semester and £9,821 (£9,719 to £9,924) per patient-year that was £1,344 (95%CI £1,222 to £1,465) less per patient-semester and £1,954 (95%CI £1,801 to £2,107) less per patient-year compared with Truvada®+EFV; healthcare costs for AIDS patients were similar across all regimens.ConclusionThe single pill regimen is as effective as the two- and three-pill regimens of the same drugs, but if started as first-line induction therapy there would be a 20% savings on healthcare costs at six and 17% of costs at twelve months compared with Truvada®+EFV, that generated the next lowest costs.

Calculate time to first-line treatment failure, annual cost and cost-effectiveness of NNRTI versus PIboosted first-line HAART regimens in the UK, 1996-2006.Population costs for HIV services are increasing in the UK and interventions need to be effective and efficient to reduce or stabilize costs. 2NRTIs + NNRTI regimens are cost-effective regimens for first-line HAART, but these regimens have not been compared with first-line PI(boosted) regimens.Times to first-line treatment failure and annual costs were calculated for first-line HAART regimens by CD4 count when starting HAART (2006 UK prices). Cost-effectiveness of 2NRTIs+NNRTI versus 2NRTIs+PI(boosted) regimens was calculated for four CD4 strata.55% of 5,541 people living with HIV (PLHIV) started HAART with CD4 count ≤ 200 cells/mm3, many of whom were Black Africans. Annual treatment cost decreased as CD4 count increased; most marked differences were observed between starting HAART with CD4 ≤ 200 cells/mm3 compared with CD4 count >200 cells/mm3. 2NRTI+PI(boosted) and 2NRTI+NNRTI regimens were the most effective regimens across the four CD4 strata; 2NRTI + NNRTI was cost-saving or cost-effective compared with 2NRTI + PI(boosted) regimens.To ensure more effective and efficient provision of HIV services, 2NRTI+NNRTI should be started as first-line HAART regimen at CD4 counts ≤ 350 cell/mm3, unless specific contra-indications exist. This will increase the number of PLHIV receiving HAART and will initially increase population costs of providing HIV services. However, starting PLHIV earlier on cost-effective regimens will maintain them in better health and use fewer health or social services, thereby generating fewer treatment and care costs, enabling them to remain socially and economically active members of society. This does raise a number of ethical issues, which will have to be acknowledged and addressed, especially in countries with limited resources.

The number of people living with HIV (PLHIV) is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997-2006 and projected them 2007-2013.Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices). Population costs were derived by multiplying the number of PLHIV by their annual cost for 1997-2006 and projected 2007-2013.Average annual treatment costs across all stages of HIV infection ranged from £17,034 in 1997 to £18,087 in 2006 for PLHIV on mono-therapy and from £27,649 in 1997 to £32,322 in 2006 for those on quadruple-or-more ART. The number of PLHIV using NHS services rose from 16,075 to 52,083 in 2006 and was projected to increase to 78,370 by 2013. Annual population cost rose from £104 million in 1997 to £483 million in 2006, with a projected annual cost between £721 and £758 million by 2013. When including community care costs, costs increased from £164 million in 1997, to £683 million in 2006 and between £1,019 and £1,065 million in 2013.Increased number of PLHIV using NHS services resulted in rising UK population costs. Population costs are expected to continue to increase, partly due to PLHIV's longer survival on ART and the relative lack of success of HIV preventing programs. Where possible, the cost of HIV treatment and care needs to be reduced without reducing the quality of services, and prevention programs need to become more effective. While high income countries are struggling to meet these increasing costs, middle- and lower-income countries with larger epidemics are likely to find it even more difficult to meet these increasing demands, given that they have fewer resources.

To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PI(boosted), comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3.Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices).cART naïve patients CD4≤200 cells/mm3 had an annual cost of £6,407 (95%CI £6,382 to £6,425) PPY compared with £2,758 (95%CI £2,752 to £2,761) PPY for those with CD4>200 cells/mm3; cost per life year gained of pre-cART treatment and care for those with CD4>200 cells/mm3 was £1,776 (cost-saving to £2,752). Annual cost for starting 2NRTIs+NNRTI or 2NRTIs+PI(boosted) with CD4≤200 cells/mm3 was £12,812 (95%CI £12,685-£12,937) compared with £10,478 (95%CI £10,376-£10,581) for PLHIV with CD4>200 cells/mm3. Cost per additional life-year gained on first-line therapy for those with CD4>200 cells/mm3 was £4639 (£3,967 to £2,960).PLHIV starting to use HIV services before CD4≤200 cells/mm3 is cost-effective and enables them to be monitored so they start cART with a CD4>200 cells/mm3, which results in better outcomes and is cost-effective. However, 25% of PLHIV accessing services continue to present with CD4≤200 cells/mm3. This highlights the need to investigate the cost-effectiveness of testing and early treatment programs for key populations in the UK.

Introduction: Untreated hearing loss is reported to negatively impact on an individual's quality of life, affecting their psychological and physical health and placing them at greater risk of developing dementia. Despite this, hearing loss management is often delayed by up to a decade. This is likely due to difficulties in navigating the hearing care pathway, and the absence of a central, unbiased reference point for consumer-friendly hearing health information and resources. We intend to co-design an online support service for adults with hearing loss with the following aims: 1) to understand unmet needs and consumer barriers to accessing hearing health information, 2) to identify solutions to these unmet needs that can be developed into prototype ideas, 3) to incrementally build on iterations of a prototype until a usable online support service is developed and ready for real-life testing with end-users, and 4) to test and evaluate the usability, accessibility, and effectiveness of the prototype from the consumer's perspective, so that the prototype can be refined into the final product., Methods and Analysis: This will be a mixed method study. Consumers will be involved in all stages of the design of the project following the Hasso Plattner model of design thinking. The qualitative component will involve sprints and semi-structured interviews to access the consumer perspective and understand unmet needs and challenges regarding the access of online hearing health information. For the quantitative component, an online survey will be administered prior to prototype testing as part of the remote usability study to collect self-efficacy and eHealth literacy outcome measures via validated questionnaires. Data collection will also be performed post-prototype testing for evaluation purposes. Finally, heuristic evaluation of the prototype will be conducted by an eLearning expert to help refine the prototype into the final product., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zou et al. This 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.)

Background: There is growing evidence of the anti-inflammatory effect of the anti-diabetic drug metformin and its use to reduce pain. However, we currently lack studies investigating whether metformin is associated with a reduction in chronic back pain prevalence when considering physical activity levels, body mass index (BMI), and age., Objective: To investigate whether use of metformin is associated with lower levels of reporting of chronic back pain in a large cohort with type 2 diabetes when stratified for physical activity, BMI, and age., Methods: This is a cross-sectional study of 21,889 participants with type 2 diabetes who were drawn from the UK Biobank database. We investigated whether people using metformin reported a higher prevalence of chronic low back pain than those who did not. Type 2 diabetes, chronic back pain, and metformin were self-reported. Participants were stratified according to their physical activity level (low, moderate and high), BMI (normal, overweight, and obese), and age (40 to <50; 50 to < 60; and ≥60 years). Logistic regression models were built for each physical activity level, BMI and age category to investigate the prevalence of chronic back pain amongst those using and not using metformin., Results: Participants who were using metformin and who had low levels of physical activity [OR 0.87, 95%CI 0.78 to 0.96] or who were obese [OR 0.90, 95%CI 0.86 to 0.98] or older [OR 0.85, 95%CI 0.78 to 0.93] had lower odds of reporting chronic back pain than their counterparts., Conclusion: The anti-diabetic drug metformin might reduce prevalence of chronic low back pain in people who are older, overweight, or less active. These findings should be confirmed in studies using a longitudinal design., Competing Interests: The authors have declared no competing interests exist., (Copyright: © 2023 Carvalho-e-Silva et al. This 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.)

Human dental pulp stem cells (hDPSCs) have increasingly gained interest as a potential therapy for nerve regeneration in medicine and dentistry, however their neurogenic potential remains a matter of debate. This study aimed to characterize hDPSC neuronal differentiation in comparison with the human SH-SY5Y neuronal stem cell differentiation model. Both hDPSCs and SH-SY5Y could be differentiated to generate typical neuronal-like cells following sequential treatment with all-trans retinoic acid (ATRA) and brain-derived neurotrophic factor (BDNF), as evidenced by significant expression of neuronal proteins βIII-tubulin (TUBB3) and neurofilament medium (NF-M). Both cell types also expressed multiple neural gene markers including growth-associated protein 43 (GAP43), enolase 2/neuron-specific enolase (ENO2/NSE), synapsin I (SYN1), nestin (NES), and peripherin (PRPH), and exhibited measurable voltage-activated Na+ and K+ currents. In hDPSCs, upregulation of acetylcholinesterase (ACHE), choline O-acetyltransferase (CHAT), sodium channel alpha subunit 9 (SCN9A), POU class 4 homeobox 1 (POU4F1/BRN3A) along with a downregulation of motor neuron and pancreas homeobox 1 (MNX1) indicated that differentiation was more guided toward a cholinergic sensory neuronal lineage. Furthermore, the Extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 significantly impaired hDPSC neuronal differentiation and was associated with reduction of the ERK1/2 phosphorylation. In conclusion, this study demonstrates that extracellular signal-regulated kinase/Mitogen-activated protein kinase (ERK/MAPK) is necessary for sensory cholinergic neuronal differentiation of hDPSCs. hDPSC-derived cholinergic sensory neuronal-like cells represent a novel model and potential source for neuronal regeneration therapies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Al-Maswary et al. This 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.)

Background: Social relationships are powerful determinants of health and inequalities in social relationships across socioeconomic status (SES) groups may contribute to social inequalities in health. This study investigates inequalities in social relationships in an international sample of persons with spinal cord injury and explores whether social gradients in relationships are moderated by the countries' socioeconomic development (SED)., Methods: Data from 12,330 participants of the International SCI Community Survey (InSCI) performed in 22 countries were used. We regressed social relationships (belongingness, relationship satisfaction, social interactions) on individual SES (education, income, employment, financial hardship, subjective status) and countries' SED (Human Development Index) using multi-level models (main effects). To test potential moderation of the SED, interaction terms between individual SES and countries' SED were entered into multi-level models., Results: Paid work, absence of financial hardship and higher subjective status were related to higher belongingness (OR, 95% CI: 1.50, 1.34-1.67; 1.76, 1.53-2.03; 1.16, 1.12-1.19, respectively), higher relationship satisfaction (OR, 95% CI: 1.28, 1.15-1.42; 1.97, 1.72-2.27; 1.20, 1.17-1.24, respectively) and fewer problems with social interactions (Coeff, 95% CI: 0.96, 0.82-1.10; 1.93, 1.74-2.12; 0.26, 0.22-0.29, respectively), whereas associations with education and income were less consistent. Main effects for countries' SED showed that persons from lower SED countries reported somewhat higher relationship satisfaction (OR, 95% CI: 0.97, 0.94-0.99) and less problems with social interactions (Coeff, 95% CI: -0.04, -0.09- -0.003). Results from moderation analysis revealed that having paid work was more important for relationships in lower SED countries, while education and subjective status were more important for relationships in higher SED countries (interaction terms p<0.05)., Conclusion: Social relationships in persons with spinal cord injury are patterned according to individual SES and the countries' SED and larger socioeconomic structures partly moderate associations between individual SES and social relationships., Competing Interests: The authors have declared that no competing interests exist.

The dimensions of patient-centred care include not only clinical effectiveness and patient safety, but, importantly, the preferences of patients as consumers of healthcare services. A total of 249 participants were included in the study, with a balanced population proportional representation by age, gender, ethnicity and geographic region of New Zealand. An online questionnaire was used to identify participants' decision-making process, and what factors and barriers for participants to seek dental treatment. Cross-tabulations, Spearman correlation analysis and Pearson Chi-Square analysis were used for the statistical analyses. Three most common reasons for visit were check-up (77%), clean (57%) and relief of pain 36%). A desire to treat a perceived problem was the most common encouraging factor to seek dental care. Cost was the most common barrier to seeking dental services. The majority of participants attended a private practice (84%), with convenience of location and referral from professionals the most likely to influence their choice. Participants felt the most important trait a dental practitioner could demonstrate was to discuss treatment options with them before any treatment. Dental check-up, teeth cleaning and relief of pain were the most common reasons for patients to choose dental services. Cost and ethnicity of the consumers had a significant impact on how dental services were perceived and sought. Dental practitioners may need to reorientate how they express value of oral health practice, not just in regard to communication with patients, but also with government funding agencies., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study evaluated whether frequent (fortnightly) audit and feedback cycles over a sustained period of time (>12 months) increased clinician adherence to recommended guidelines in acquired brain injury rehabilitation., Design: A before and after study design., Setting: A metropolitan inpatient brain injury rehabilitation unit., Participants: Clinicians; medical, nursing and allied health staff., Interventions: Fortnightly cycles of audit and feedback for 14 months. Each fortnight, medical file and observational audits were completed against 114 clinical indicators., Main Outcome Measure: Adherence to guideline indicators before and after intervention, calculated by proportions, Mann-Whitney U and Chi square analysis., Results: Clinical and statistical significant improvements in median clinical indicator adherence were found immediately following the audit and feedback program from 38.8% (95% CI 34.3 to 44.4) to 83.6% (95% CI 81.8 to 88.5). Three months after cessation of the intervention, median adherence had decreased from 82.3% to 76.6% (95% CI 72.7 to 83.3, p<0.01). Findings suggest that there are individual indicators which are more amenable to change using an audit and feedback program., Conclusion: A fortnightly audit and feedback program increased clinicians' adherence to guideline recommendations in an inpatient acquired brain injury rehabilitation setting. We propose future studies build on the evidence-based method used in the present study to determine effectiveness and develop an implementation toolkit for scale-up., Competing Interests: The authors have declared that no competing interests exist.

The adverse long-term consequences following traumatic brain injury are poorly understood, particularly on the cerebral microvasculature. Retinal vessels are a surrogate marker of cerebral vascular changes. We therefore aimed to examine the cross-sectional association between serious head injury or being knocked unconscious, and/or concussion and retinal microvascular signs, specifically, mean retinal arteriolar and venular calibre, in older adults after accounting for potential confounders. This cohort study involved 2,624 adults with mean age of 66.9 (±9.1) years who self-reported head injury and concussion parameters, and had gradable retinal photographs. Face-to-face interviews with trained interviewers allowed participants to report prior serious head injury or being knocked unconscious, and/or a previous diagnosis of concussion by a medical professional. Fundus photographs were taken and retinal vascular calibre measured using computer-assisted techniques and summarized. There were 25.9%, 15.3% and 10.1% who reported a prior serious head injury or being "knocked unconscious", concussion, and both, respectively. Participants in the first group compared to non-injured participants had significantly wider (~2 μm) mean retinal venular calibre (p = 0.02), after adjusting for age, sex, smoking, body mass index, mean arterial blood pressure, type 2 diabetes and fellow vessel calibre. No significant associations were observed in people reporting medically diagnosed concussion or with mean retinal arteriolar calibre. Our exploratory study suggests that head injury is independently associated with wider retinal venular caliber. These findings warrant further investigation in longitudinal cohort studies., Competing Interests: The authors have declared that no competing interests exist.

Objective: To assess the effect of non-fluoride agents on the prevention of dental caries in primary dentition., Materials and Methods: Medline, Web of Science, Embase, Cochrane Library, CBM and CNKI databases were searched to identify all the relevant articles published prior to 16 December 2016. Grey literature was also searched. Randomized controlled human clinical trials in which non-fluoride agents were delivered by any method were considered., Results: Of the 1,236 studies screened, 39 full articles were scrutinized and 14 selected for inclusion in the final sample. Five chemical agents, namely arginine, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), chlorhexidine, triclosan and xylitol were investigated in these included studies. The cariostatic effects of non-fluoride agents in vivo were evaluated in comparison with fluoride or placebos in randomized controlled trials. There is evidence that the use of certain doses of xylitol may be effective in arresting dental caries in primary dentition. However, quantitative synthesis could not be carried out because of the clinical and methodological heterogeneity of the included studies., Conclusions: A study at low risk of bias indicated that daily use of xylitol wipes is a useful adjunct for caries control in young children, however, this conclusion should be interpreted with caution as this study had a very limited sample size. Chlorhexidine and CPP-ACP may be more effective than a placebo in managing caries in primary dentition, but their effectiveness is borderline when compared with fluoride. Arginine-containing mint confection and 0.3% triclosan varnish were found to reduce caries development in primary teeth but the evidence was at high risk of bias. High quality randomized controlled trials are needed in order to make a conclusive recommendation.

Azole antifungals, known as demethylase inhibitors (DMIs), target sterol 14α-demethylase (CYP51) in the ergosterol biosynthetic pathway of fungal pathogens of both plants and humans. DMIs remain the treatment of choice in crop protection against a wide range of fungal phytopathogens that have the potential to reduce crop yields and threaten food security. We used a yeast membrane protein expression system to overexpress recombinant hexahistidine-tagged S. cerevisiae lanosterol 14α-demethylase and the Y140F or Y140H mutants of this enzyme as surrogates in order characterize interactions with DMIs. The whole-cell antifungal activity (MIC50 values) of both the R- and S-enantiomers of tebuconazole, prothioconazole (PTZ), prothioconazole-desthio, and oxo-prothioconazole (oxo-PTZ) as well as for fluquinconazole, prochloraz and a racemic mixture of difenoconazole were determined. In vitro binding studies with the affinity purified enzyme were used to show tight type II binding to the yeast enzyme for all compounds tested except PTZ and oxo-PTZ. High resolution X-ray crystal structures of ScErg11p6×His in complex with seven DMIs, including four enantiomers, reveal triazole-mediated coordination of all compounds and the specific orientation of compounds within the relatively hydrophobic binding site. Comparison with CYP51 structures from fungal pathogens including Candida albicans, Candida glabrata and Aspergillus fumigatus provides strong evidence for a highly conserved CYP51 structure including the drug binding site. The structures obtained using S. cerevisiae lanosterol 14α-demethylase in complex with these agrochemicals provide the basis for understanding the impact of mutations on azole susceptibility and a platform for the structure-directed design of the next-generation of DMIs., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: the research was funded by Bayer Crop Science. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Low activity levels in inpatient rehabilitation are associated with adverse outcomes. The study aimed to test whether activity levels can be increased by the provision of monitored activity data to patients and clinicians in the context of explicit goal setting., Methods: A randomized controlled trial in three sites in Australia included 255 inpatients aged 60 and older who had a rehabilitation goal to become ambulant. The primary outcome was patients' walking time measured by accelerometers during the rehabilitation admission. Walking times from accelerometry were made available daily to treating therapists and intervention participants to motivate patients to improve incidental activity levels and reach set goals. For the control group, 'usual care' was followed, including the setting of mobility goals; however, for this group, neither staff nor patients received data on walking times to aid the setting of daily walking time targets., Results: The median daily walking time in the intervention group increased from 10.3 minutes at baseline to 32.1 minutes at day 28, compared with an increase from 9.5 to 26.5 minutes per day in the control group. Subjects in the intervention group had significantly higher non-therapy walking time by about 7 minutes [mean (95% CI): 24.6 (21.7, 27.4)] compared to those in the control group [mean(95% CI): 17.3 (14.4, 20.3)] (p = 0.001)., Conclusions: Daily feedback to patients and therapists using an accelerometer increased walking times during rehabilitation admissions. The results of this study suggest objective monitoring of activity levels could provide clinicians with information on clinically important, mobility-related activities to assist goal setting., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12611000034932 http://www.ANZCTR.org.au/., Competing Interests: The authors have declared that no competing interests exist.

Background: Consumer satisfaction with the acute-care experience could reasonably be expected to be higher amongst those treated in the private sector compared to those treated in the public sector given the former relies on high-level satisfaction of its consumers and their subsequent recommendations to thrive. The primary aims of this study were to determine, in a knee or hip arthroplasty cohort, if surgery in the private sector predicts greater overall satisfaction with the acute-care experience and greater likelihood to recommend the same hospital. A secondary aim was to determine whether satisfaction across a range of service domains is also higher in the private sector., Methods: A telephone survey was conducted 35 days post-surgery. The hospital cohort comprised eight public and seven private high-volume arthroplasty providers. Consumers rated overall satisfaction with care out of 100 and likeliness to recommend their hospital on a 5-point Likert scale. Additional Likert-style questions were asked covering specific service domains. Generalized estimating equation models were used to analyse overall satisfaction (dichotomised as ≥ 90 or < 90) and future recommendations for care (dichotomised as 'definitely recommend' or 'other'), whilst controlling for covariates. The proportions of consumers in each sector reporting the best Likert response for each individual domain were compared using non-parametric tests., Results: 457 survey respondents (n = 210 private) were included. Less patient-reported joint impairment pre-surgery [OR 1.03 (95% CI 1.01-1.05)] and absence of an acute complication (OR 2.13 95% CI 1.41-3.23) significantly predicted higher overall satisfaction. Hip arthroplasty [OR 1.84 (1.1-2.96)] and an absence of an acute complication [OR 2.31 (1.28-4.17] significantly predicted greater likelihood for recommending the hospital. The only care domains where the private out-performed the public sector were hospitality (46.7 vs 35.6%, p <0.01) and frequency of surgeon visitation (76.4 vs 65.8%, p = 0.03)., Conclusions: Arthroplasty consumers treated in the private sector are not more satisfied with their acute-care experience nor are they more likely to recommend their hospital provider. Rather, avoidance of complications in either sector appears to result in improved satisfaction as well as a greater likelihood that patients would recommend their hospital provider.

Introduction: The use of functional assessments to evaluate patient change is complicated by a lack of consensus as to which assessment is most suitable for use with older adults., Objective: To identify and appraise the properties of assessments used to evaluate functional abilities in older adults., Methods: A systematic review of randomised controlled trials of occupational therapy interventions was conducted up to 2012 to identify assessments used to measure function. Two authors screened and extracted data independently. A second search then identified papers investigating measurement properties of each assessment. Studies from the second search were included if: i) published in English, ii) the assessment was not modified from its original published form, iii) study aim was to evaluate the quality of the tool, iv) and was original research. Translated versions of assessments were excluded. Measurement quality was rated using the COSMIN checklist and Terwee criteria., Results: Twenty-eight assessments were identified from the systematic search of occupational therapy interventions provided to older adults. Assessments were of varied measurement quality and many had been adapted (although still evaluated as though the original tool had been administered) potentially altering the conclusions drawn about measurement quality. Synthesis of best evidence established 15 functional assessments have not been tested in an older adult population., Conclusions: The Functional Autonomy Measurement System (SMAF) appears to be a promising assessment for use with older adults. Only two tools (the SMAF and the Assessment of Motor and Process Skills (AMPS)) were deemed to be responsive to change when applied to older adults. Health professionals should use functional assessments that have been validated with their population and in their setting. There are reliable and valid assessments to capture the functional performance of older adults in community and hospital settings, although further refinement of these assessments may be necessary.

Objective: To identify a novel class of inhibitors of fungal transporters involved in drug resistance., Methods: A series of structurally-related low molecular mass compounds was synthesized using combinatorial chemistry of a cyclobutene-dione (squarile) core. These compounds were screened for their inhibition of plasma membrane Major Facilitator Superfamily (MFS) and ATP-binding cassette (ABC) transporters responsible for efflux pump-mediated drug resistance in the fungal pathogen Candida albicans. Strains of Saccharomyces cerevisiae that specifically overexpress the MFS pump CaMdr1p or the ABC transporter CaCdr1p were used in primary screens and counterscreens, respectively, and to detect inhibition of glucose-dependent Nile Red efflux. Efflux pump inhibition, activity as pump substrates and antifungal activity against yeast and clinical isolates expressing efflux pumps were determined using agarose diffusion susceptibility assays and checkerboard liquid chemosensitization assays with fluconazole., Results: The screen identified five structurally-related compounds which inhibited CaMdr1p. Two compounds, A and B, specifically chemosensitized AD/CaMDR1 to FLC in a pH-dependent fashion and acted synergistically with FLC in checkerboard liquid MIC assays but compound B had limited solubility. Compound A chemosensitized to FLC the azole-resistant C. albicans strain FR2, which over-expresses CaMdr1p, inhibited Nile Red efflux mediated by CaMdr1p but not CaCdr1p and was not toxic to cultured human cells. A minor growth-inhibitory effect of B on AD/CaMDR1, but not on AD/CaCDR1 and AD/CaCDR2, indicated that compound B may be a substrate of these transporters. The related compound F was found to have antifungal activity against the three pump over-expressing strains used in the study., Conclusions: Compound A is a 'first in class' small molecule inhibitor of MFS efflux pump CaMdr1p.

Background: Given the aging demographics of most developed countries, understanding the public health impact of mild/moderate road traffic crash injuries in older adults is important. We aimed to determine whether health outcomes (pain severity and quality of life measures) over 24 months differ significantly between older (65+) and younger adults (18-64)., Methods: Prospective cohort study of 364, 284 and 252 participants with mild/moderate injury following a vehicle collision at baseline, 12 and 24 months, respectively. A telephone-administered questionnaire obtained information on socio-economic, pre- and post-injury psychological and heath characteristics., Results: At baseline, there were 55 (15.1%) and 309 (84.9%) participants aged ≥65 and 18-64 years, respectively. At 12- and 24-month follow-up, older compared to younger participants who had sustained a mild/moderate musculoskeletal injury had lower physical functioning (3.9-units lower Short Form-12 Physical Composite Score, multivariable-adjusted p = 0.03 at both examinations). After multivariable adjustment, older (n = 45) versus younger (n = 207) participants had lower self-perceived health status (8.1-units lower European Quality of Life-5 Dimensions Visual Acuity Scale scores at 24 months, p = 0.03), 24 months later., Conclusions: Older compared to younger participants who sustained a mild/moderate injury following a road-traffic crash demonstrated poorer physical functioning and general health at 24 months.

The effect of financial compensation on health outcomes following musculoskeletal injury requires further exploration because results to date are varied and controversial. This systematic review identifies compensation related factors associated with poorer health outcomes following musculoskeletal injury. Searches were conducted using electronic medical journal databases (Medline, CINAHL, Embase, Informit, Web of Science) for prospective studies published up to October 2012. Selection criteria included: prognostic factors associated with validated health outcomes; six or more months follow up; and multivariate statistical analysis. Studies solely measuring return to work outcomes were excluded. Twenty nine articles were synthesised and then assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to determine evidence levels. The results were mixed. There was strong evidence of an association between compensation status and poorer psychological function; and legal representation and poorer physical function. There was moderate evidence of an association between compensation status and poorer physical function; and legal representation and poorer psychological function. There was limited evidence of an association between compensation status and increased pain. In seven studies the association depended on the outcome measured. No studies reported an association between compensation related factors and improved health outcomes. Further research is needed to find plausible reasons why compensation related factors are associated with poorer health following musculoskeletal injury.

The transition from terrestrial ancestry to a fully pelagic life profoundly altered the body systems of cetaceans, with extreme morphological changes in the skull and feeding apparatus. The Oligocene Epoch was a crucial time in the evolution of cetaceans when the ancestors of modern whales and dolphins (Neoceti) underwent major diversification, but details of dental structure and evolution are poorly known for the archaeocete-neocete transition. We report the morphology of teeth and ultrastructure of enamel in archaeocetes, and fossil platanistoids and delphinoids, ranging from late Oligocene (Waitaki Valley, New Zealand) to Pliocene (Caldera, Chile). Teeth were embedded in epoxy resin, sectioned in cross and longitudinal planes, polished, etched, and coated with gold palladium for scanning electron microscopy (SEM) observation. SEM images showed that in archaeocetes, squalodontids and Prosqualodon (taxa with heterodont and nonpolydont/limited polydont teeth), the inner enamel was organized in Hunter-Schreger bands (HSB) with an outer layer of radial enamel. This is a common pattern in most large-bodied mammals and it is regarded as a biomechanical adaptation related to food processing and crack resistance. Fossil Otekaikea sp. and delphinoids, which were polydont and homodont, showed a simpler structure, with inner radial and outer prismless enamel. Radial enamel is regarded as more wear-resistant and has been retained in several mammalian taxa in which opposing tooth surfaces slide over each other. These observations suggest that the transition from a heterodont and nonpolydont/limited polydont dentition in archaeocetes and early odontocetes, to homodont and polydont teeth in crownward odontocetes, was also linked to a marked simplification in the enamel Schmelzmuster. These patterns probably reflect functional shifts in food processing from shear-and-mastication in archaeocetes and early odontocetes, to pierce-and-grasp occlusion in crownward odontocetes, with the implication of less demanding feeding biomechanics as seen in most extant odontocetes.

Bite mark injuries often feature in violent crimes. Conventional morphometric methods for the forensic analysis of bite marks involve elements of subjective interpretation that threaten the credibility of this field. Human DNA recovered from bite marks has the highest evidentiary value, however recovery can be compromised by salivary components. This study assessed the feasibility of matching bacterial DNA sequences amplified from experimental bite marks to those obtained from the teeth responsible, with the aim of evaluating the capability of three genomic regions of streptococcal DNA to discriminate between participant samples. Bite mark and teeth swabs were collected from 16 participants. Bacterial DNA was extracted to provide the template for PCR primers specific for streptococcal 16S ribosomal RNA (16S rRNA) gene, 16S-23S intergenic spacer (ITS) and RNA polymerase beta subunit (rpoB). High throughput sequencing (GS FLX 454), followed by stringent quality filtering, generated reads from bite marks for comparison to those generated from teeth samples. For all three regions, the greatest overlaps of identical reads were between bite mark samples and the corresponding teeth samples. The average proportions of reads identical between bite mark and corresponding teeth samples were 0.31, 0.41 and 0.31, and for non-corresponding samples were 0.11, 0.20 and 0.016, for 16S rRNA, ITS and rpoB, respectively. The probabilities of correctly distinguishing matching and non-matching teeth samples were 0.92 for ITS, 0.99 for 16S rRNA and 1.0 for rpoB. These findings strongly support the tenet that bacterial DNA amplified from bite marks and teeth can provide corroborating information in the identification of assailants.