White Paper: Open Digital Health - accelerating transparent and scalable health promotion and treatment.

In this White Paper, we outline recommendations from the perspective of health psychology and behavioural science, addressing three research gaps: (1) What methods in the health psychology research toolkit can be best used for developing and evaluating digital health tools? (2) What are the most feasible strategies to reuse digital health tools across populations and settings? (3) What are the main advantages and challenges of sharing (openly publishing) data, code, intervention content and design features of digital health tools? We provide actionable suggestions for researchers joining the continuously growing Open Digital Health movement, poised to revolutionise health psychology research and practice in the coming years. This White Paper is positioned in the current context of the COVID-19 pandemic, exploring how digital health tools have rapidly gained popularity in 2020-2022, when world-wide health promotion and treatment efforts rapidly shifted from face-to-face to remote delivery. This statement is written by the Directors of the not-for-profit Open Digital Health initiative (n = 6), Experts attending the European Health Psychology Society Synergy Expert Meeting (n = 17), and the initiative consultant, following a two-day meeting (19-20th August 2021).

Treating Peripheral Arterial Occlusive Disease and Acute Limb Ischemia During a COVID-19 Pandemic in 2020.

BACKGROUND: For many surgeons the outbreak of SARS-CoV-2 meant a downscaling of surgical interventions. The aim of this study was to investigate the impact of the measures taken on the care for patients with peripheral arterial disease (PAOD) and acute limb ischemia (ALI). METHODS: A retrospective analysis of the vascular practices of 2 major teaching hospitals in the Netherlands was performed. All interventions and outpatient visits for PAOD or ALI in 2020 were included. Patients treated in 2018 and 2019 were to serve as a control group. Data were analysed using descriptive statistics. RESULTS: In 2020, a total of 1513 procedures were performed for PAOD or ALI. This did not differ significantly from previous years. Overall, Fontaine 2 and 4 were the most frequent indications for intervention. A significant increase in the number of major amputations was observed in 2020 compared to 2018 (P< 0.01). This was mainly due to patients suffering from PAOD Fontaine 4. Inversely, a reduction in the number of femoro-popliteal bypasses was observed between 2020 and 2018. The number of outpatient visit due to Fontaine 2 was significantly lower in 2020 compared to 2018. CONCLUSIONS: The vascular practices of our hospitals were minimally influenced by the measures taken due to the outbreak of SARS-CoV-2. There was an increase in the number of amputation but an enormous surge in patients presenting with critical limb ischemia was not observed.

Treatment outcomes and safety in children with rifampicin-resistant TB.

BACKGROUND: The treatment of rifampicin-resistant TB (RR-TB) in children is evolving rapidly. As newer regimens are introduced into routine care, it is vital to compare their outcome and safety with well-characterised clinical cohorts treated with historical regimens.METHODS: Study sample comprised a prospective observational cohort of children on routine RR-TB treatment, enrolled from 2011 to 2015 in Cape Town, South Africa. Children were followed for safety, treatment response and outcome.RESULTS: Of 136 children included, 27 (19.9%) were living with HIV and 48 (37.8%) had severe TB. The median time-to-culture conversion in children with bacteriological confirmation (n = 44) was 28.5 days (IQR 14.5-45). Overall, 118/129 (91.5%) had favourable TB treatment outcomes. Of 106 (77.9%) children who received an injectable drug, 9 (8.5%) developed hearing loss and 7/136 (5.1%) developed other Grade 3 or higher adverse events likely related to treatment.CONCLUSIONS: In this cohort with a substantial proportion of children with severe manifestations of TB and with HIV, TB treatment outcomes were excellent. Apart from hearing loss, few children developed severe adverse events related to treatment. This study provides robust reference data for future evaluation of shorter, injectable-sparing regimens.

Examining the neural correlates of goal priming with the NeuroShop, a novel virtual reality fMRI paradigm.

OBJECTIVE: Health goal priming has been shown to stimulate healthy food choices by activating an individual's weight-control goal. The present study combined fMRI with a novel virtual reality food choice task to elucidate the underlying neural mechanisms of health goal priming. Previous research has suggested that the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) play a role in the incorporation of health considerations into the food choice process. Responses may be more representative for those found in real life when assessed in an environment similar to the actual choice environment. Therefore, the first aim of the study was to explore if a novel virtual reality food choice task is sufficiently sensitive to detect basic valuation processes in food choice. The second aim was to examine whether increased activation in the dlPFC drives the effects of health goal priming. METHODS: Fifty-six female participants performed an fMRI food choice task embedded in a virtual supermarket environment. They chose between perceived healthy and unhealthy products in a health prime, hedonic prime, and non-food control condition, while activation in brain areas involved in self-control and valuation (vmPFC, dlPFC) was assessed. RESULTS: There were no differences in relative preference for perceived healthy products over unhealthy products between the conditions. There were also no main effects of prime condition on brain activation in the vmPFC and dPFC during food choice. Across conditions, activation in the vmPFC correlated with the tastiness of the chosen product during food choice. CONCLUSIONS: Although the study does not provide support for health goal priming triggering neural self-control mechanisms, results did show that virtual reality has potential for a more realistic fMRI food choice paradigm.

A Comparison of Health Status and Quality of Life in Patients with Intermittent Claudication.

BACKGROUND: Patient reported outcome measures (PROMs) such as health status (HS) and quality of life (QOL) are frequently used interchangeably while they represent different outcomes. Whether a discrepancy exists in patients with intermittent claudication (IC) in changes over time between HS and QOL is unclear. This study aimed to investigate the strength and the direction of the association between HS and QOL over time in patients with IC that underwent supervised exercise therapy (SET). MATERIAL AND METHODS: Patients were part of the ELECT multi-center prospective cohort study. One goal of this study was to obtain data on HS and QOL at different time intervals of patients with IC that underwent SET. HS (VascuQOL-6) and QOL (WHOQOL-BREF) were completed at baseline, 3 months, and 6 months follow up. Pearson's correlation coefficients and the associated common variances (R2) were calculated to measure the strength and the direction of the association between HS and QOL in changes between baseline and follow-up moments. RESULTS: In total, 177 patients were included in data analyses. Only changes in physical QOL and overall QOL had a small correlation with changes over time in HS, at both 3- and 6 months follow up (respectively R2=.14; P < 0.001 and R2 = 0.12; P < 0.001 for physical QOL and R2 = 0.18; P < 0.001 and R2 = 0.13; P < 0.001 for overall QOL). CONCLUSIONS: This study showed that HS and QOL provide different outcomes in patients with IC that underwent SET. Future studies should be aware of these differences before PROMs are being incorporated as an outcome measure in clinical studies.

Pharmacokinetics of high-dose isoniazid in children affected by multidrug-resistant TB.

BACKGROUND: High-dose isoniazid (INHH) (15-20 mg/kg/day) could be administered to overcome low-level INH resistance, but pharmacokinetic data are sparse.METHODS: This observational study included South African children (<15 years) receiving INHH as preventive therapy, or treatment for multidrug-resistant TB (MDR-TB) exposure or disease. Pharmacokinetic sampling was performed after an INH dose of 20 mg/kg. Non-compartmental analysis and multivariable regression models were used to evaluate associations of key covariates with area under the curve (AUC0-24) and maximum concentration (Cmax). AUC and Cmax values were compared against proposed adult targets.RESULTS: Seventy-seven children were included, with median age of 3.7 years; 51 (66%) had MDR-TB disease and 26 (34%) had MDR-TB exposure. Five were HIV-positive, of whom four were ≥5 years old. The median AUC0-24 was 19.46 µgh/mL (IQR 10.76-50.06) and Cmax was 5.14 µg/mL (IQR 2.69-13.2). In multivariable analysis of children aged <5 years, MDR-TB disease (vs. exposure) was associated with considerably lower AUC0-24 (geometric mean ratio GMR 0.19, 95% CI 0.15-0.26; P < 0.001) and Cmax (GMR 0.20, 95% CI 0.15-0.26; P < 0.001).CONCLUSIONS: INH concentrations in children with MDR-TB disease were much lower than expected, but comparable to previous reports in children with MDR-TB exposure. Further studies should confirm these findings and explore possible causes.

Circulating endothelial cells transiently increase in peripheral blood after kidney transplantation.

The diagnosis of kidney allograft rejection is based on late histological and clinical markers. Early, specific and minimally-invasive biomarkers may improve rejection diagnosis. Endothelial cells (EC) are one of the earliest targets in kidney transplant rejection. We investigated whether circulating EC (cEC) could serve as an earlier and less invasive biomarker for allograft rejection. Blood was collected from a cohort of 51 kidney transplant recipients before and at multiple timepoints after transplantation, including during a for cause biopsy. The number and phenotype of EC was assessed by flow-cytometric analysis. Unbiased selection of EC was done using principal component (PCA) analysis. Paired analysis revealed a transient cEC increase of 2.1-fold on the third day post-transplant, recovering to preoperative levels at seventh day post-transplant and onwards. Analysis of HLA subtype demonstrated that cEC mainly originate from the recipient. cEC levels were not associated with allograft rejection, allograft function or other allograft pathologies. However, cEC in patients with allograft rejection and increased levels of cEC showed elevated levels of KIM-1 (kidney injury marker-1). These findings indicate that cEC numbers and phenotype are affected after kidney transplantation but may not improve rejection diagnosis.

The Subjective Value of Product Popularity: A Neural Account of How Product Popularity Influences Choice Using a Social and a Quality Focus.

Research on social influences often distinguishes between social and quality incentives to ascribe meaning to the value that popularity conveys. This study examines the neural correlates of those incentives through which popularity influences preferences. This research reports an functional magnetic resonance imaging experiment and a behavioral task in which respondents evaluated popular products with three focus perspectives; unspecified focus, focus on social aspects, and focus on quality. The results show that value derived with a social focus reflects inferences of approval and reward value, and positively affects preferences. Value derived with a quality (versus normal) focus reflects inferences of quality and negatively affects preferences. This study provides evidence of two distinct inferential routes on both a neurological level, represented by different regions in the brain, and a behavioral level. These results provide the first evidence that a single popularity cue can in different ways influence the value derived from product popularity.

Caregiver strain on informal caregivers when providing care for older patients undergoing major abdominal surgery: a longitudinal prospective cohort study.

BACKGROUND: Health-care systems nowadays rely on complementary patient care by informal caregivers. The need for, and burden on, informal caregivers will likely increase in the upcoming years. This study aimed to examine the burden on caregivers when providing care for elderly patients undergoing major abdominal surgery. METHODS: A single-centre longitudinal cohort study was conducted between November 2015 and June 2018 in the Amphia hospital in Breda, the Netherlands. Patients aged 70+ undergoing elective surgery for colorectal carcinoma (CRC) or an abdominal aortic aneurysm (AAA) were included in this study. Informal caregiver burden was assessed and compared over time using the Caregiver Strain Index (CSI) at the outpatient clinic visit, at discharge, 2 weeks post-discharge and after 6 and 12 months. The effects of patient- and caregiver-related factors on the experienced caregiver strain were examined. RESULTS: CSI scores of 248 caregivers were significantly increased at discharge (3.5 vs 2.6; p < 0.001) and 2 weeks post-discharge (3.3 vs 2.6; p < 0.001). After 12 months, scores dropped below baseline scores (1.8 vs 2.6; p = 0.012). The highest strain was observed 2 weeks post-discharge for AAA patients and at discharge for CRC patients. Older age, physical or cognitive impairment and burden of comorbidity were associated with an increased caregiver strain at baseline. Type of surgery was independently associated with the change in mean CSI scores over time; a bigger change in caregiver burden is observed after open surgery. CONCLUSION: In the early postoperative period, perceived caregiver strain was significantly increased. Psychological support for caregivers may be advisable, with timing of this support depending on diagnosis and patient-related factors. TRIAL REGISTRATION: This manuscript was retrospectively registered on 05-04-2016 in the Netherlands Trial Register (NTR5932). http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5932.

Effect of conservative treatment in aortoiliac occlusive disease.

Objective: To determine the effect of primary conservative treatment without revascularization in patients with proven aortoiliac occlusive disease (AIOD) presenting with intermittent claudication (IC).Background: The initial treatment of IC should focus on supervised exercise therapy (SET) and pharmacotherapy. Nowadays, primary endovascular revascularization (EVR) has become increasingly popular in patients with all types of AIOD. But in daily practice, EVR is often performed without initially extensive exercise.Method: This is a single centre retrospective study from December 2012 to September 2017. Primary outcomes were maximum walking distance (MWD) and patient satisfaction. Secondary outcomes were revascularization rate and mortality.Results: Twenty-four patients were included. Mean age was 64 years (SD: 9). Mean follow-up was 28 months (SD: 17). Nineteen patients (80%) had SET. In 18 (75%) patients, the MWD was improved compared to the initial situation. In five (21%) patients, the MWD stayed the same. The MWD of one (4%) patient decreased. Overall satisfaction rate was 87%. Three patients (13%) were not satisfied with the conservative treatment and eventually got an EVR. There was no disease related death.Conclusions: Conservative treatment, especially with SET, has acceptable subjective symptom outcomes in selected patients with AIOD. It could be a good alternative treatment for certain patients with AIOD and IC.

Risk factors for postoperative delirium after elective major abdominal surgery in elderly patients: A cohort study.

BACKGROUND: Prehabilitation programs have recently been suggested as potentially able to lower the incidence of delirium in elderly patients undergoing major abdominal surgery. For these prehabilitation programs to become successful, it is essential to identify those patients who are most likely to develop a delirium. MATERIAL AND METHODS: A single-centre cohort study was conducted. Inclusion criteria were: age ≥70 years and scheduled for abdominal surgery for colorectal cancer or an abdominal aortic aneurysm between January 2013 and June 2018. Baseline patient, surgical, anaesthesiologic and haematological characteristics were collected. A risk factor analysis was conducted, with postoperative delirium as primary outcome, by performing a multivariable logistic regression analysis. RESULTS: In this study, 627 patients were included, of whom 64 (10%) developed a delirium. Variables that differed significantly between delirious and non-delirious patients were age, burden of comorbidity, renal impairment, hypertension, cognitive impairment, history of delirium, physical and nutritional impairment, open surgery, preoperative anaemia and erythrocyte transfusion. After multivariable logistic regression analysis, risk factors for postoperative delirium after major abdominal surgery were renal impairment (OR 2.2; 95%CI 1.2-4.3), cognitive impairment (OR 4.1; 95%CI 1.8-9.2), an ASA score ≥ 3 (OR 2.0; 95% CI 1.0-3.9), being an active smoker (OR 2.7; 95%CI 1.3-5.8), ICU admission (OR 7.1; 95%CI 3.5-14.3), erythrocyte transfusion (OR 2.4; 95%CI 1.2-4.9) and a diagnosis of colorectal cancer (CRC); (OR 4.0; 95% CI 1.7-9.6). Prehabilitation had a protective effect (OR 0.5; 95% CI 0.3-0.9). CONCLUSION: Postoperative delirium is a frequent complication after major abdominal surgery in the elderly, especially in octogenarians and after open procedures. Renal impairment, cognitive impairment, being an active smoker, ICU admission, erythrocyte transfusion and a diagnosis of CRC are important risk factors for the development of delirium. Prehabilitation lowers the risk of developing a delirium.

Prevention of postoperative delirium in elderly patients planned for elective surgery: systematic review and meta-analysis.

Introduction: Vulnerable or "frail" patients are susceptible to the development of delirium when exposed to triggers such as surgical procedures. Once delirium occurs, interventions have little effect on severity or duration, emphasizing the importance of primary prevention. This review provides an overview of interventions to prevent postoperative delirium in elderly patients undergoing elective surgery. Methods: A literature search was conducted in March 2018. Randomized controlled trials (RCTs) and before-and-after studies on interventions with potential effects on postoperative delirium in elderly surgical patients were included. Acute admission, planned ICU admission, and cardiac patients were excluded. Full texts were reviewed, and quality was assessed by two independent reviewers. Primary outcome was the incidence of delirium. Secondary outcomes were severity and duration of delirium. Pooled risk ratios (RRs) were calculated for incidences of delirium where similar intervention techniques were used. Results: Thirty-one RCTs and four before-and-after studies were included for analysis. In 19 studies, intervention decreased the incidences of postoperative delirium. Severity was reduced in three out of nine studies which reported severity of delirium. Duration was reduced in three out of six studies. Pooled analysis showed a significant reduction in delirium incidence for dexmedetomidine treatment, and bispectral index (BIS)-guided anaesthesia. Based on sensitivity analyses, by leaving out studies with a high risk of bias, multicomponent interventions and antipsychotics can also significantly reduce the incidence of delirium. Conclusion: Multicomponent interventions, the use of antipsychotics, BIS-guidance, and dexmedetomidine treatment can successfully reduce the incidence of postoperative delirium in elderly patients undergoing elective, non-cardiac surgery. However, present studies are heterogeneous, and high-quality studies are scarce. Future studies should add these preventive methods to already existing multimodal and multidisciplinary interventions to tackle as many precipitating factors as possible, starting in the pre-admission period.

Multimodal prehabilitation to reduce the incidence of delirium and other adverse events in elderly patients undergoing elective major abdominal surgery: An uncontrolled before-and-after study.

BACKGROUND: Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients. METHODS: A single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and October 2015 (control group) and between November 2015 and June 2018 (prehabilitation group). The prehabilitation group received interventions to improve patients' physical health, nutritional status, factors of frailty and preoperative anaemia prior to surgery. The primary outcome was incidence of delirium, diagnosed with the DSM-V criteria or the confusion assessment method. Secondary outcomes were additional complications, length of stay, unplanned ICU admission, length of ICU stay, readmission rate, institutionalization, and in-hospital or 30-day mortality. RESULT: A total of 360 control patients and 267 prehabilitation patients were included in the final analysis. The mean number of prehabilitation days was 39 days. The prehabilitation group had a higher burden of comorbidities and was more physically and visually impaired at baseline. At adjusted logistic regression analysis, delirium incidence was reduced significantly from 11.7 to 8.2% (OR 0.56; 95% CI 0.32-0.98; P = 0.043). No statistically significant effects were seen on secondary outcomes. CONCLUSION: Current prehabilitation program is feasible and safe, and can reduce delirium incidence in elderly patients undergoing elective major abdominal surgery. This program merits further evaluation. TRIAL REGISTRATION: Dutch Trial Registration, NTR5932.

The Role of Delirium and Other Risk Factors on Mortality in Elderly Patients with Critical Limb Ischemia Undergoing Major Lower Limb Amputation.

BACKGROUND: Delirium in patients with critical limb ischemia (CLI) is associated with increased mortality. The main goal of this study was to investigate the association between delirium and mortality in patients undergoing major lower limb amputation for CLI. In addition, other risk factors associated with mortality were analyzed. METHODS: An observational cohort study was conducted including all patients aged ≥70 years with CLI undergoing a major lower limb amputation between January 2014 and July 2017. Delirium was scored using the Delirium Observation Screening Score in combination with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Risk factors for mortality were analyzed by calculating hazard ratios using a Cox proportional hazards model. RESULTS: In total, 95 patients were included; of which, 29 (31%) patients developed a delirium during admission. Delirium was not associated with an increased risk of mortality (hazard ratio [HR] = 0.84; 95 % confidence interval [CI]: 0.51-1.73; P = 0.84). Variables independently associated with an increased risk of mortality were age (HR 1.1; 95% CI 1.0-1.1), cardiac history (HR 3.3; 95% CI 1.8-6.1), current smoking (HR 2.9; 95% CI 1.6-5.5), preoperative anemia (HR 2.8; 95% CI 1.1-7.2), and living in a nursing home (HR 2.2; 95% CI 1.1-4.4). CONCLUSION: Delirium was not associated with an increased mortality risk in elderly patients with CLI undergoing a major lower limb amputation. Factors related to an increased mortality risk were age, cardiac history, current smoking, preoperative anemia, and living in a nursing home.

Use of Serum MicroRNAs as Biomarker for Hepatobiliary Diseases in Dogs.

BACKGROUND: Current biochemical indicators cannot discriminate between parenchymal, biliary, vascular, and neoplastic hepatobiliary diseases. MicroRNAs are promising new biomarkers for hepatobiliary disease in humans and dogs. OBJECTIVE: To measure serum concentrations of an established group of microRNAs in dogs and to investigate their concentrations in various types of hepatobiliary diseases. ANIMALS: Forty-six client-owned dogs with an established diagnosis of hepatobiliary disease and stored serum samples and eleven client-owned healthy control Labrador Retrievers. METHODS: Retrospective study. Medical records of dogs with parenchymal, biliary, vascular, or neoplastic hepatobiliary diseases and control dogs were reviewed. Concentrations of miR-21, miR-122, miR-126, miR-148a, miR-200c, and miR-222 were quantified in serum by real-time polymerase chain reaction. RESULTS: No different microRNA concentrations were found in the adenoma and congenital portosystemic shunt groups. In all other diseases, miR-122 concentrations were elevated with the highest concentration in the mucocele group (267-fold, CI: 40-1,768, P < .001). In dogs with biliary diseases, miR-21 and miR-222 were only increased in dogs with mucoceles (26-fold, CI: 5-141, P = .005 and 13-fold, CI: 2-70, P = .025, respectively). Uniquely increased microRNAs were found in the hepatocellular carcinoma group (miR-200c, 35-fold increase, CI: 3-382, P = .035) and the chronic hepatitis group (miR-126, 22-fold increase, CI: 5-91, P = .002). CONCLUSIONS AND CLINICAL IMPORTANCE: A microRNA panel consisting of miR-21, miR-122, miR-126, miR-200c, and miR-222 can distinguish between parenchymal, biliary, and neoplastic hepatobiliary diseases. Serum microRNA profiling is a promising new tool that might be a valuable addition to conventional diagnostics to help diagnose various hepatobiliary diseases in dogs.

Risk factors of post-operative delirium after elective vascular surgery in the elderly: A systematic review.

BACKGROUND: Postoperative delirium is a common and serious adverse event in the elderly patient and is associated with significant morbidity and mortality. It is of great importance to identify patients at risk for delirium, in order to focus preventive strategies. The aim of this article is to systematically review current available literature on pre-operative risk factors for delirium after vascular surgery. METHODS: A systematic literature search was conducted using PubMed and EMBASE, using the MeSH terms and key words "delirium", "surgery" and "risk factor". Studies were retained for review after meeting strict inclusion criteria that included only prospective studies evaluating risk factors for delirium in patients who had elective vascular surgery. Diagnosis of delirium needed to be confirmed using the Diagnostic and Statistical Manual of Mental Disorders (DSM) or ICD-10. RESULTS: Fifteen articles were selected for inclusion, incidence of delirium across the studies ranged from 5% to 39%. Many factors have been associated with increased risk of delirium, including age, cognitive impairment, comorbidity, depression, smoking, alcohol, visual and hearing impairment, ASA-score, biochemical abnormalities, operative strategies and blood loss. CONCLUSIONS: Delirium is a common complication after elective vascular surgery in elderly. The highest delirium incidence was observed after open aortic surgery as well as after surgery for critical limb ischemia. A picture starts to form of which predisposing factors lead to increased risk of delirium. The leading risk factors consistently identified in this systematic review were advanced age and cognitive impairment. Multi-disciplinary specialist-led interventions in the preoperative phase could decrease incidence and severity of delirium and should be focused on identified high-risk patients.

Evaluation of Staphylococcus aureus Eradication Therapy in Vascular Surgery.

INTRODUCTION: Surgical site infections (SSI) are a serious complication in vascular surgery which may lead to severe morbidity and mortality. Staphylococcus aureus nasal carriage is associated with increased risk for development of SSIs in central vascular surgery. The risk for SSI can be reduced by perioperative eradication of S. aureus carriage in cardiothoracic and orthopedic surgery. This study analyzes the relation between S. aureus eradication therapy and SSI in a vascular surgery population. METHODS: A prospective cohort study was performed, including all patients undergoing vascular surgery between February 2013 and April 2015. Patients were screened for S. aureus nasal carriage and, when tested positive, were subsequently treated with eradication therapy. The presence of SSI was recorded based on criteria of the CDC. The control group consisted of a cohort of vascular surgery patients in 2010, who were screened, but received no treatment. RESULTS: A total of 444 patients were screened. 104 nasal swabs were positive for S. aureus, these patients were included in the intervention group. 204 patients were screened in the 2010 cohort. 51 tested positive and were included in the control group. The incidence of S. aureus infection was 5 out of 51 (9.8%) in the control group versus 3 out of 104 in the eradication group (2.2%; 95% confidence interval 0.02-1.39; P = 0.13). A subgroup analysis showed that the incidence of S. aureus infection was 3 out of 23 (13.0%) in the control group in central reconstructive surgery versus 0 out of 44 in the intervention group (P = 0.074). The reduction of infection pressure by S. aureus was stronger than the reduction of infection pressure by other pathogens (exact maximum likelihood estimation; OR = 0.0724; 95% CI: 0.001-0.98; p = 0.0475). CONCLUSION: S. aureus eradication therapy reduces the infection pressure of S. aureus, resulting in a reduction of SSIs caused by S. aureus.

Bioavailability of two licensed paediatric rifampicin suspensions: implications for quality control programmes.

SETTING: To assess the revised World Health Organization-recommended dose of 10-20 mg/kg rifampicin (RMP), we studied the steady state pharmacokinetics of RMP in South African children who received standard treatment for drug-susceptible tuberculosis (TB). OBJECTIVE: To determine the formulation effect on the pharmacokinetics of RMP. DESIGN: RMP plasma concentrations were characterised in 146 children (median age 1.4 years, range 0.2-10.2). The morning dose on the day of the pharmacokinetic evaluation was administered as one of two RMP single-drug oral suspensions. RESULTS: While one formulation achieved 2 h concentrations in the range of those observed in adults (median 6.54 mg/l, interquartile range [IQR] 4.47-8.84), the other attained a median bioavailability of only 25% of this, with a median 2 h concentration of 1.59 mg/l (IQR 0.89-2.38). CONCLUSION: RMP is a key drug for the treatment of TB. It is critical that the quality of RMP suspensions used to treat childhood TB is ensured.

Hepatocyte-derived microRNAs as sensitive serum biomarkers of hepatocellular injury in Labrador retrievers.

Common parenchymal liver diseases in dogs include reactive hepatopathies and primary hepatitis (acute or chronic). In chronic hepatitis, there is usually a long subclinical phase. Specific clinical signs become overt only when liver damage is severe and in this phase, treatment is usually less effective. Limited data are available regarding the sensitivity of liver enzyme activity or biomarkers for early detection of subclinical hepatitis. Hepatocyte-derived microRNAs (HDmiRs) were recently identified as promising biomarkers for hepatocellular injury in multiple species. Here, the potential of the HDmiRs miR-122 and miR-148a as sensitive diagnostic biomarkers for hepatocellular injury in Labrador retrievers was investigated. Samples from 66 Labrador retrievers with histologically normal livers, high hepatic copper, and with various forms of liver injury were evaluated for serum alanine aminotransferase (ALT) activity and microRNA values. Median values of HDmiR-122 were 34.6 times higher in dogs with liver injury and high ALT than in normal dogs (95% confidence intervals [CI], 13-95; P <0.001). HDmiR-122 values were significantly increased in dogs with liver injury and normal ALT (4.2 times; 95% CI, 2-12; P <0.01) and in dogs with high hepatic copper concentrations and unremarkable histopathology (2.9 times; 95% CI, 1.1-8.0; P <0.05). Logistic regression analyses demonstrated that miR-122 and miR-148a were both predictors of hepatocellular injury. The sensitivity of miR-122 was 84% (95% CI, 73-93%), making it superior to ALT (55%; 95% CI, 41-68%) for the detection of hepatocellular injury in Labrador retrievers (P <0.001). This study demonstrated that serum HDmiR, particularly miR-122, is a highly sensitive marker for the detection of hepatocellular injury in Labrador retrievers and is a promising new biomarker that may be used for early detection of subclinical hepatitis in dogs.