ObjectivesTo investigate whether there is an association between differences in travel time/travel distance to healthcare services and patients' health outcomes and assimilate the methodologies used to measure this.DesignSystematic Review. We searched MEDLINE, Embase, Web of Science, Transport database, HMIC and EBM Reviews for studies up to 7 September 2016. Studies were excluded that included children (including maternity), emergency medical travel or countries classed as being in the global south.SettingsA wide range of settings within primary and secondary care (these were not restricted in the search).Results108 studies met the inclusion criteria. The results were mixed. 77% of the included studies identified evidence of a distance decay association, whereby patients living further away from healthcare facilities they needed to attend had worse health outcomes (eg, survival rates, length of stay in hospital and non-attendance at follow-up) than those who lived closer. 6 of the studies identified the reverse (a distance bias effect) whereby patients living at a greater distance had better health outcomes. The remaining 19 studies found no relationship. There was a large variation in the data available to the studies on the patients' geographical locations and the healthcare facilities attended, and the methods used to calculate travel times and distances were not consistent across studies.ConclusionsThe review observed that a relationship between travelling further and having worse health outcomes cannot be ruled out and should be considered within the healthcare services location debate.

Vitamin D is widely recognized as a hormone that is important for calcium homeostasis and maintenance of skeletal health. Vitamin D also plays a role in the function of the immune system (1-4). In vitro data have shown that 1,25-dihydroxyvitamin D (1,25[OH] 2 D) inhibits T cell proliferation and decreases the production of Th1 cytokines interleukin-2, interferon-␥, and tumor necrosis factor ␣ (5). Further, in vivo studies suggest that 1,25(OH) 2 D supplementation prevents the initiation and progression of inflammatory arthritis (collagen-induced arthritis) in rodents and prevents experimental autoimmune encephalomyelitis (a murine model used to determine the efficacy of drugs for the treatment of multiple sclerosis) (6,7).Additional evidence of an immunomodulating role of vitamin D in rheumatoid arthritis (RA) includes the localization of vitamin D receptors to macrophages, chondrocytes, and synoviocytes in tissues, such as rheu-

IntroductionIt has been suggested that doctors in their first year of post-graduate training make a disproportionate number of prescribing errors.ObjectiveThis study aimed to compare the prevalence of prescribing errors made by first-year post-graduate doctors with that of errors by senior doctors and non-medical prescribers and to investigate the predictors of potentially serious prescribing errors.MethodsPharmacists in 20 hospitals over 7 prospectively selected days collected data on the number of medication orders checked, the grade of prescriber and details of any prescribing errors. Logistic regression models (adjusted for clustering by hospital) identified factors predicting the likelihood of prescribing erroneously and the severity of prescribing errors.ResultsPharmacists reviewed 26,019 patients and 124,260 medication orders; 11,235 prescribing errors were detected in 10,986 orders. The mean error rate was 8.8 % (95 % confidence interval [CI] 8.6–9.1) errors per 100 medication orders. Rates of errors for all doctors in training were significantly higher than rates for medical consultants. Doctors who were 1 year (odds ratio [OR] 2.13; 95 % CI 1.80–2.52) or 2 years in training (OR 2.23; 95 % CI 1.89–2.65) were more than twice as likely to prescribe erroneously. Prescribing errors were 70 % (OR 1.70; 95 % CI 1.61–1.80) more likely to occur at the time of hospital admission than when medication orders were issued during the hospital stay. No significant differences in severity of error were observed between grades of prescriber. Potentially serious errors were more likely to be associated with prescriptions for parenteral administration, especially for cardiovascular or endocrine disorders.ConclusionThe problem of prescribing errors in hospitals is substantial and not solely a problem of the most junior medical prescribers, particularly for those errors most likely to cause significant patient harm. Interventions are needed to target these high-risk errors by all grades of staff and hence improve patient safety.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-015-0320-x) contains supplementary material, which is available to authorized users.

ObjectiveTo examine the role of the variants of the PTPN22 and HLA–DRB1 genes as predictors of mortality in inflammatory polyarthritis (IP) and rheumatoid arthritis (RA).MethodsPatients were recruited from a primary care–based inception cohort of patients with IP and were followed up prospectively. For patients who died, the cause and date of death was obtained. Cox proportional hazards regression models were used to assess the association of the HLA–DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti–cyclic citrullinated peptide (anti-CCP) status, adjusted by age at symptom onset and sex.ResultsDNA samples were available from 1,022 IP patients. During followup, 751 of them (74%) satisfied the American College of Rheumatology 1987 criteria for RA, and 242 of them (24%) died. Carriage of 2 copies of SE alleles predicted death from all causes (hazard ratio [HR] 1.57 [95% confidence interval (95% CI) 1.1–2.2]) and from CVD (HR 1.68 [95% CI 1.1–2.7]). This effect was most marked for individuals with the HLA–DRB1*01/*04 combination. An interaction of smoking, SE alleles, and anti-CCP antibodies was observed and was associated with the greatest risk of death from CVD (HR 7.81 [95% CI 2.6–23.2]). No association of the PTPN22 gene with mortality was detected.ConclusionSE alleles, particularly compound heterozygotes, are associated with death from all causes and from CVD, independently of autoantibody status. However, the combination of SE, smoking, and anti-CCP antibodies is associated with a high risk of premature death in patients with IP and RA, which raises the possibility of a targeted strategy to prevent CVD in these patients.

ReuseThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) licence. This licence only allows you to download this work and share it with others as long as you credit the authors, but you can't change the article in any way or use it commercially. More information and the full terms of the licence here: https://creativecommons.org/licenses/ TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. AbstractBackground: Electronic personal health records (ePHRs) are web-based tools that enable patients to access parts of their medical records and other services. In spite of the potential benefits of using ePHRs, their adoption rates remain very low. The lack of use of ePHRs among patients leads to implementation failures of these systems. Many studies have been conducted to examine the factors that influence patients' use of ePHRs, and they need to be synthesised in a meaningful way.Objective: The current study aimed to systematically review the evidence regarding factors that influence patients' use of ePHRs.Methods: The search included: 42 bibliographic databases (e.g. Medline, Embase, CINHAL, and PsycINFO), hand searching, checking reference lists of the included studies and relevant reviews, contacting experts, and searching two general web engines. Study selection, data extraction, and study quality assessment were carried out by two reviewers independently. The quality of studies was appraised using the Mixed Methods Appraisal Tool. The extracted data were synthesised narratively according to the outcome: intention to use, subjective measures of use, and objective measures of use. The identified factors were categorised into groups based on Or and Karsh's conceptual framework.Results: Of 5225 citations retrieved, 97 studies were relevant to this review. These studies examined more than 150 different factors: 59 related to intention to use, 52 regarding subjectively-measured use, and 105 related to objectively-measured use. The current review was able to draw definitive conclusions regarding the effect of only 18 factors. Of these, only three factors have been investigated in connection with every outcome, which are: perceived usefulness, privacy and security concerns, and internet access. Conclusion: Of the numerous factors examined by the included studies, this review concluded the effect of 18 factors: 13 personal factors (e.g. gender, ethnicity, and income), four humantechnology factors (e.g. perceived usefulness and ease of use), and one organisational factor (facilitating conditions). These factors should be taken into account by stakeholders for the successful implementation of these systems. For example, patients should be assured that the system is secure and no one can access their records without their permission in order to decrease their concerns about the privacy and security. Fur...

Due to the cross-sectional nature of previous studies, whether mechanical factors predict the onset of Chronic oro-facial pain remains unclear. Aims of the current study were to test the hypotheses that self-reported mechanical factors would predict onset of Chronic oro-facial pain and that any observed relationship would be independent of the confounding effects of psychosocial factors and reporting of other unexplained symptoms. About 1735 subjects who had completed a baseline questionnaire were assessed at 2 year follow-up for the presence of Chronic oro-facial pain, psychosocial factors (anxiety and depression, illness behaviour, life stressors and reporting of somatic symptoms), mechanical dysfunction (facial trauma, grinding, phantom bite and missing teeth) and reporting of other unexplained symptoms (chronic widespread pain, irritable bowel syndrome and chronic fatigue). About 1329 subjects returned completed questionnaires (adjusted response rate 87%). About 56 (5%) reported new episodes of Chronic oro-facial pain at follow-up. Univariate analyses showed that age, gender, reporting of other unexplained symptoms, psychosocial factors and two self-report mechanical factors predicted the onset of Chronic oro-facial pain. However multivariate analysis showed that mechanical factors did not independently predict onset. The strongest predictors were health anxiety (Relative Risk (RR) 2.8, 95% CI 1.3–6.2), chronic widespread pain (RR 4.0 95% C.I. 2.2–7.4) and age (RR 0.2, 95% CI 0.1–0.7). The findings from this prospective study support the hypothesis that psychosocial factors are markers for onset of Chronic oro-facial pain. The efficacy of early psychological management of Chronic oro-facial pain to address these factors should be a priority for future investigations.

Objective. Few data exist on the use of anti-TNF drugs for AS during routine clinical use in the UK. This report describes an improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) after 6 months of therapy in 261 patients enrolled in a national prospective observational register.Methods. The British Society for Rheumatology Biologics Register (BSRBR) recruited patients starting anti-TNF therapy for AS between 2002 and 2006. Multivariable linear regression models were used to estimate the predictors of absolute improvement in BASDAI and BASFI at 6 months. Covariates included age, gender, disease duration, baseline BASDAI and BASFI, presence of raised inflammatory markers (defined as twice the upper limit of normal) and DMARD therapy.Results. The cohort was young (median age 43 years) and 82% were males. Median baseline BASDAI was 7.6 and BASFI 7.9. At 6 months, the mean improvements in BASDAI and BASFI were 3.6 and 2.6 U, respectively; 52% reached a BASDAI50. Patients with raised inflammatory markers at the start of therapy had a 0.9-U (95% CI 0.2, 1.5) better improvement in BASDAI compared with those without. Lesser responses were seen in those with higher baseline BASFI scores. Women had a 1.1-U (95% CI 0.3, 2.0) greater improvement in BASFI at 6 months, as did those who were receiving concurrent DMARD therapy [0.9 U (95% CI 0.2, 1.7)].Conclusions. The majority of patients receiving anti-TNF therapy for AS during routine care demonstrated an improvement in disease activity. Raised inflammatory markers at the start of therapy predicted a greater improvement in BASDAI, identifying a group of patients who may be more responsive to anti-TNF therapies, although the results were not confined to this group.

Premature infants are frequently exposed to aminoglycoside antibiotics. Novel urinary biomarkers may provide a non-invasive means for the early identification of aminoglycoside-related proximal tubule renal toxicity, to enable adjustment of treatment and identification of infants at risk of long-term renal impairment. In this proof-of-concept study, urine samples were collected from 41 premature neonates (≤32 weeks gestation) at least once per week, and daily during courses of gentamicin, and for 3 days afterwards. Significant increases were observed in the three urinary biomarkers measured (Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-associated Lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG)) during treatment with multiple courses of gentamicin. When adjusted for potential confounders, the treatment effect of gentamicin remained significant only for KIM-1 (mean difference from not treated, 1.35 ng/mg urinary creatinine; 95% CI 0.05–2.65). Our study shows that (a) it is possible to collect serial urine samples from premature neonates, and that (b) proximal tubule specific urinary biomarkers can act as indicators of aminoglycoside-associated nephrotoxicity in this age group. Further studies to investigate the clinical utility of novel urinary biomarkers in comparison to serum creatinine need to be undertaken.