Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

OVPSYCH2: A randomized controlled trial of psychological support versus standard of care following chemotherapy for ovarian cancer.

BACKGROUND: Fear of disease progression (FOP) is a rational concern for women with Ovarian Cancer (OC) and depression is also common. To date there have been no randomized trials assessing the impact of psychological intervention on depression and FOP in this patient group. PATIENTS AND METHODS: Patients with primary or recurrent OC who had recently completed chemotherapy were eligible if they scored between 5 and 19 on the PHQ-9 depression and were randomized 1:1 to Intervention (3 standardized CBT-based sessions in the 6-12 weeks post-chemotherapy) or Control (standard of care). PHQ-9, FOP-Q-SF, EORTC QLQ C30 and OV28 questionnaires were then completed every 3 months for up to 2 years. The primary endpoint was change in PHQ-9 at 3 months. Secondary endpoints were change in other scores at 3 months and all scores at later timepoints. RESULTS: 182 patients registered; 107 were randomized; 54 to Intervention and 53 to Control; mean age 59 years; 75 (70%) had completed chemotherapy for primary and 32 (30%) for relapsed OC and 67 patients completed both baseline and 3-month questionnaires. Improvement in PHQ-9 was observed for patients in both study arms at three months compared to baseline but there was no significant difference in change between Intervention and Control. A significant improvement on FOP-Q-SF scores was seen in the Intervention arm, whereas for those in the Control arm FOP-Q-SF scores deteriorated at 3 months (intervention effect = -4.4 (-7.57, -1.22), p-value = 0.008). CONCLUSIONS: CBT-based psychological support provided after chemotherapy did not significantly alter the spontaneously improving trajectory of depression scores at three months but caused a significant improvement in FOP. Our findings call for the routine implementation of FOP support for ovarian cancer patients.

Targeting GM-CSF for collagenase-induced osteoarthritis pain and disease in mice.

OBJECTIVES: Pharmacological options for treating osteoarthritis (OA) are limited and alternative treatments are required. Given the clinical data indicating that granulocyte macrophage-colony stimulating factor (GM-CSF) may be a therapeutic target in human OA, we evaluated different treatment regimens with a neutralizing anti-GM-CSF monoclonal antibody (mAb) in an experimental OA model to determine their effectiveness on amelioration of pain and disease. METHODS: The collagenase-induced osteoarthritis (CiOA) model was induced in C57BL/6 mice, followed by different treatment regimens of anti-GM-CSF mAb or isotype control. Anti-CCL17 mAb treatment was also administered continually during the late stage of CiOA. Pain-related behavior (change in weight distribution of hind limbs), and disease (cartilage damage and osteophyte size) were assessed. RESULTS: Blocking GM-CSF only during early synovitis in CiOA prevented pain and disease development. Once OA pain was established, regardless of the treatment regimen, anti-GM-CSF mAb treatment rapidly and efficiently ameliorated it; however, unless the treatment was continued, pain returned and disease progressed. Continual late stage blockade of GM-CSF was able to ameliorate pain (between-group difference: -6.567; 95% confidence interval (CI): -10.12, -3.011) and suppress cartilage damage (P = 0.0317, 95% CI: -1.75, -0.0556). Continual late stage blockade of CCL17 showed similar effects on pain and disease development. CONCLUSIONS: Early and short-term GM-CSF neutralization is effective at preventing CiOA pain and disease development but, once pain is evident, continual GM-CSF blockade is required to prevent pain from returning and to suppress disease progression in mice. These data reinforce the potential benefits of anti-GM-CSF (and anti-CCL17) mAb therapy in OA and should inform further clinical trials.

Early cardiac remodeling in aortic coarctation: insights from fetal and neonatal functional and structural assessment.

OBJECTIVES: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation. METHODS: This was a prospective observational case-control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age-matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA-affected heart specimen, using synchrotron radiation-based X-ray phase-contrast microcomputed tomography and histology, respectively. RESULTS: We included 30 fetuses with CoA and 60 gestational age-matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left-to-right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0-2.7) vs 1.8 (1.7-2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1-84.9) vs 47.0 (43.0-55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct. CONCLUSIONS: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume-loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial.

BACKGROUND: STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. METHODS: We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. RESULTS: Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). CONCLUSIONS: The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

Recurrence of Clostridium difficile infection in the Western Australian population.

Clostridium difficile, the most common cause of hospital-associated diarrhoea in developed countries, presents major public health challenges. The high clinical and economic burden from C. difficile infection (CDI) relates to the high frequency of recurrent infections caused by either the same or different strains of C. difficile. An interval of 8 weeks after index infection is commonly used to classify recurrent CDI episodes. We assessed strains of C. difficile in a sample of patients with recurrent CDI in Western Australia from October 2011 to July 2017. The performance of different intervals between initial and subsequent episodes of CDI was investigated. Of 4612 patients with CDI, 1471 (32%) were identified with recurrence. PCR ribotyping data were available for initial and recurrent episodes for 551 patients. Relapse (recurrence with same ribotype (RT) as index episode) was found in 350 (64%) patients and reinfection (recurrence with new RT) in 201 (36%) patients. Our analysis indicates that 8- and 20-week intervals failed to adequately distinguish reinfection from relapse. In addition, living in a non-metropolitan area modified the effect of age on the risk of relapse. Where molecular epidemiological data are not available, we suggest that applying an 8-week interval to define recurrent CDI requires more consideration.

Comparison of two prognostic models in trauma outcome.

BACKGROUND: The Trauma Audit and Research Network (TARN) in the UK publicly reports hospital performance in the management of trauma. The TARN risk adjustment model uses a fractional polynomial transformation of the Injury Severity Score (ISS) as the measure of anatomical injury severity. The Trauma Mortality Prediction Model (TMPM) is an alternative to ISS; this study compared the anatomical injury components of the TARN model with the TMPM. METHODS: Data from the National Trauma Data Bank for 2011-2015 were analysed. Probability of death was estimated for the TARN fractional polynomial transformation of ISS and compared with the TMPM. The coefficients for each model were estimated using 80 per cent of the data set, selected randomly. The remaining 20 per cent of the data were used for model validation. TMPM and TARN were compared using calibration curves, measures of discrimination (area under receiver operating characteristic curves; AUROC), proximity to the true model (Akaike information criterion; AIC) and goodness of model fit (Hosmer-Lemeshow test). RESULTS: Some 438 058 patient records were analysed. TMPM demonstrated preferable AUROC (0·882 for TMPM versus 0·845 for TARN), AIC (18 204 versus 21 163) and better fit to the data (32·4 versus 153·0) compared with TARN. CONCLUSION: TMPM had greater discrimination, proximity to the true model and goodness-of-fit than the anatomical injury component of TARN. TMPM should be considered for the injury severity measure for the comparative assessment of trauma centres.

Three-Dimensional Fermi Surface of Overdoped La-Based Cuprates.

We present a soft x-ray angle-resolved photoemission spectroscopy study of overdoped high-temperature superconductors. In-plane and out-of-plane components of the Fermi surface are mapped by varying the photoemission angle and the incident photon energy. No k_{z} dispersion is observed along the nodal direction, whereas a significant antinodal k_{z} dispersion is identified for La-based cuprates. Based on a tight-binding parametrization, we discuss the implications for the density of states near the van Hove singularity. Our results suggest that the large electronic specific heat found in overdoped La_{2-x}Sr_{x}CuO_{4} cannot be assigned to the van Hove singularity alone. We therefore propose quantum criticality induced by a collapsing pseudogap phase as a plausible explanation for observed enhancement of electronic specific heat.

Temporal relationship between occurrences of hand, foot and mouth disease, respiratory virus detection and febrile seizures in children in tropical Singapore: a time-series analysis.

Febrile seizure (FS) in children is a common complication of infections with respiratory viruses and hand, foot and mouth disease (HFMD). We conducted a retrospective ecological time-series analysis to determine the temporal relationship between hospital attendances for FS and HFMD or respiratory virus infections. Epilepsy attendance was used as a control. Data from 2004 to 2012 FS and epilepsy hospital attendance, HFMD notifications to the Ministry of Health and from laboratory-confirmed viral respiratory infections among KK Women's and Children's Hospital inpatients were used. A multivariate linear regression analysis was conducted to evaluate the relationship between FS and the virus time series. Relative risks of FS by age were calculated using Bayesian statistical methods. Paediatric accident and emergency (A&E) attendances for FS were found to be associated with influenza A (extra 0.47 FS per influenza A case), B (extra 0.32 per influenza B case) and parainfluenza 3 (extra 0.35 per parainfluenza type 3 case). However, other viruses were not significantly associated with FS. None of the viruses were associated with epileptic seizure attendance. Influenza A, B and parainfluenza 3 viruses contributed to the burden of FS resulting in A&E attendance. Children at risk of FS should be advised to receive seasonal influenza vaccination.

Feasibility of a streamlined imaging protocol in technetium-99m-Tektrotyd somatostatin receptor SPECT/CT.

AIM: To assess the feasibility and efficacy of a streamlined single time-point 99mTc-HYNIC-Tyr3-octreotide (Tektrotyd) somatostatin receptor scintigraphy (SRS) protocol to differentiate pathological uptake by neuroendocrine tumours (NETs) from physiological activity. METHODS AND MATERIALS: Tektrotyd imaging in 50 consecutive patients with NETs was reviewed retrospectively. Imaging was independently assessed by two experienced reporters with dual-certification in radiology and nuclear medicine and agreed in consensus. The presence of physiological bowel activity and/or further sites of equivocal uptake on 4-hour planar imaging and whether combined single-photon-emission computed tomography (SPECT)/computed tomography (CT) assessment allowed accurate diagnosis was tabulated. A judgement was also made in each case on whether 2-hour planar imaging was necessary for accurate diagnostic interpretation. RESULTS: Thirty-six patients (72%) had positive findings on Tektrotyd SPECT/CT. Eight patients (16%) had bowel activity on 4-hour planar imaging, which could be considered to have hampered interpretation without access to SPECT/CT. Eleven studies in 10 patients (20%) demonstrated areas of indeterminate uptake on planar imaging; five in the uncinate process of the pancreas, three in the nasal cavity or paranasal sinuses, one in the adrenal glands, one in a focus of inflammation on the posterior abdominal wall, and one at the tip of a central venous line. In all cases, accurate interpretation of findings was possible with SPECT/CT, without the 2-hour planar image. CONCLUSION: Two-hour planar imaging could be safely omitted from Tektrotyd SRS incorporating SPECT/CT imaging without reducing the accuracy of diagnostic interpretation. Streamlined imaging has the potential to reduce patient inconvenience and improve scanner and staff efficiency.

Calibration of a high spectral resolution lidar using a Michelson interferometer, with data examples from ORACLES.

The NASA Langley airborne second-generation High Spectral Resolution Lidar (HSRL-2) uses a density-tuned field-widened Michelson interferometer to implement the HSRL technique at 355 nm. The Michelson interferometer optically separates the received backscattered light between two channels, one of which is dominated by molecular backscattering, while the other contains most of the light backscattered by particles. This interferometer achieves high and stable contrast ratio, defined as the ratio of particulate backscatter signal received by the two channels. We show that a high and stable contrast ratio is critical for precise and accurate backscatter and extinction retrievals. Here, we present retrieval equations that take into account the incomplete separation of particulate and molecular backscatter in the measurement channels. We also show how the accuracy of the contrast ratio assessment propagates to error in the optical properties. For both backscattering and extinction, larger errors are produced by underestimates of the contrast ratio (compared to overestimates), more extreme aerosol loading, and-most critically-smaller true contrast ratios. We show example results from HSRL-2 aboard the NASA ER-2 aircraft from the 2016 ORACLES field campaign in the southeast Atlantic, off the coast of Africa, during the biomass burning season. We include a case study where smoke aerosol in two adjacent altitude layers showed opposite differences in extinction- and backscatter-related Ångström exponents and a reversal of the lidar ratio spectral dependence, signatures which are shown to be consistent with a relatively modest difference in smoke particle size.

The relationship between process use and stage of change for sugary drinks.

BACKGROUND: Decreasing sugar-sweetened beverage consumption may reduce obesity and obesity-related diseases. To better understand what processes could facilitate a reduction in sugary beverage intake, we examined the relationship between stage-of-change and use of 10 processes of change. Secondarily, reliability of the measure was assessed. METHODS: A cross-sectional study was conducted, using a newly developed stage-of-change and process of change questionnaire. Participants (n = 105; male, n = 28) were aged between 18 and 60 years. A one-way analysis of variance, with Tukey's and Benjamini-Hochberg post hoc tests, was used to compare process use by stages. Paired t-tests were used to compare total cognitive and total behavioural process use within each stage. Cronbach's α coefficient and mean inter-item correlation was used to assess internal consistency. Reliability of repeated items was examined using kappa. RESULTS: Cognitive and behavioural processes were used more in the contemplation/preparation and maintenance stages than in precontemplation (all P < 0.05). Compared to precontemplation, process use was significantly higher in contemplation/preparation for five individual processes, action for four processes and maintenance for five processes. The use of dramatic relief and self liberation was lower in maintenance than contemplation/preparation. Across the stages, the use of eight of the 10 processes differed. The use of consciousness raising, self re-evaluation and self liberation differed between stages more frequently than other processes. CONCLUSIONS: The use of many processes differed by stage and could be incorporated into programmes aiming to assist adults in reducing their consumption of sugary drinks.

Laparoscopic pyloromyotomy for hypertrophic pyloric stenosis: a survey of 407 children.

INTRODUCTION: Pyloromyotomy is the standard care for hypertrophic pyloric stenosis. The traditional approach for this procedure is a right upper quadrant transverse incision, although other "open" approaches, such as circumumbilical or periumbilical incision have been described. The more recent approach used is laparoscopic pyloromyotomy (LP), but experience feedback is still debated and its benefits remain unproven. The aim of this study was to make a review of all our LP procedures with an objective evaluation according to the literature. METHODS: A retrospective analysis of all the LPs performed in one University Children's Hospital between 1 January 1996, and 30 December 2015 was realized. Information regarding the patient's status, intraoperative and postoperative data was analyzed. RESULTS: 407 patients were included in this study. The mean operative time of the overall procedure was 24 ± 13 min, which significantly increased with the length of the pyloric muscle (p = 0.004) and significantly impacted the full feeding time (p = 0.006). 3.4% required conversion to an open procedure during the LP. We observed a significant correlation between conversion for mucosal perforation and weight loss (p = 0.04) and between conversion for mucosal perforation and preoperative weight (p = 0.002). A redo procedure was indicated in 3.7%, for incomplete pyloromyotomy each time. The mean postoperative hospital length of stay for all procedures was 1.6 ± 0.8 days. There were no inflammatory scars. None had incisional hernias or wound dehiscence. DISCUSSION: LP procedure appeared to be as quick as the open procedure. Our results were similar to others series for intraoperative complications. According to operative time, this technique does not have an impact on operative room utilization. Vomiting duration at presentation in HPS does not seem to have a significant impact on postoperative outcomes. LP procedure causes little pain during the postoperative period. No wound complications were registered.

Fetal median sacral artery anatomy study by micro-CT imaging.

PURPOSE: The median sacral artery (MSA) is the termination of the dorsal aorta, which undergoes a complex regression and remodeling process during embryo and fetal development. The MSA contributes to the pelvic vascularization and may be injured during pelvic surgery. The embryological steps of MSA development, anastomosis formation and anatomical variations are linked, but not fully understood. METHODS: The pelvic vascularization and more precisely the MSA of a human fetus at 22 weeks of gestation (GW) were studied using micro-CT imaging. Image treatment included arterial segmentations and 3D visualization. RESULTS: At 22 GW, the MSA was a well-developed straight artery in front of the sacrum and was longer than the abdominal aorta. Anastomoses between the MSA and the internal pudendal arteries and the superior rectal artery were detected. No evidence was found for the existence of a coccygeal glomus with arteriovenous anastomosis. CONCLUSIONS: Micro-CT imaging and 3D visualization helped us understand the MSA central role in pelvic vascularization through the ilio-aortic anastomotic system. It is essential to know this anastomotic network to treat pathological conditions, such as sacrococcygeal teratomas and parasitic ischiopagus twins (for instance, fetus in fetu and twin-reversed arterial perfusion sequence).

Friedreich's ataxia: clinical features, pathogenesis and management.

INTRODUCTION: Friedreich's ataxia is the most common inherited ataxia. SOURCES OF DATA: Literature search using PubMed with keywords Friedreich's ataxia together with published papers known to the authors. AREAS OF AGREEMENT: The last decade has seen important advances in our understanding of the pathogenesis of disease. In particular, the genetic and epigenetic mechanisms underlying the disease now offer promising novel therapeutic targets. AREAS OF CONTROVERSY: The search for effective disease-modifying agents continues. It remains to be determined whether the most effective approach to treatment lies with increasing frataxin protein levels or addressing the metabolic consequences of the disease, for example with antioxidants. AREAS TIMELY FOR DEVELOPING RESEARCH: Management of Freidreich's ataxia is currently focussed on symptomatic management, delivered by the multidisciplinary team. Phase II clinical trials in agents that address the abberrant silencing of the frataxin gene need to be translated into large placebo-controlled Phase III trials to help establish their therapeutic potential.

Improved Adherence to Antiretroviral Therapy Observed Among HIV-Infected Children Whose Caregivers had Positive Beliefs in Medicine in Sub-Saharan Africa.

A high level of adherence to antiretroviral treatment is essential for optimal clinical outcomes in HIV infection, but measuring adherence is difficult. We investigated whether responses to a questionnaire eliciting caregiver beliefs in medicines were associated with adherence of their child (median age 2.8 years), and whether this in turn was associated with viral suppression. We used the validated beliefs in medicine questionnaire (BMQ) to measure caregiver beliefs, and medication event monitoring system caps to measure adherence. We found significant associations between BMQ scores and adherence, and between adherence and viral suppression. Among children initiating Antiretroviral therapy (ART), we also found significant associations between BMQ 'necessity' scores, and BMQ 'necessity-concerns' scores, and later viral suppression. This suggests that the BMQ may be a valuable tool when used alongside other adherence measures, and that it remains important to keep caregivers well informed about the long-term necessity of their child's ART.

Predicting arboviral disease emergence using Bayesian networks: a case study of dengue virus in Western Australia.

A Bayesian Belief Network (BBN) for assessing the potential risk of dengue virus emergence and distribution in Western Australia (WA) is presented and used to identify possible hotspots of dengue outbreaks in summer and winter. The model assesses the probabilities of two kinds of events which must take place before an outbreak can occur: (1) introduction of the virus and mosquito vectors to places where human population densities are high; and (2) vector population growth rates as influenced by climatic factors. The results showed that if either Aedes aegypti or Ae. albopictus were to become established in WA, three centres in the northern part of the State (Kununurra, Fitzroy Crossing, Broome) would be at particular risk of experiencing an outbreak. The model can also be readily extended to predict the risk of introduction of other viruses carried by Aedes mosquitoes, such as yellow fever, chikungunya and Zika viruses.

The role of symptomatic presentation in influenza A transmission risk.

Computer models can be useful in planning interventions against novel strains of influenza. However such models sometimes make unsubstantiated assumptions about the relative infectivity of asymptomatic and symptomatic cases, or conversely assume there is no impact at all. Using household-level data from known-index studies of virologically confirmed influenza A infection, the relationship between an individual's infectiousness and their symptoms was quantified using a discrete-generation transmission model and Bayesian Markov chain Monte Carlo methods. It was found that the presence of particular respiratory symptoms in an index case does not influence transmission probabilities, with the exception of child-to-child transmission where the donor has phlegm or a phlegmy cough.

Contacts of healthcare workers, patients and visitors in general wards in Singapore.

To characterize contacts in general wards, a prospective survey of healthcare workers (HCWs), patients and visitors was conducted using self-reported diary, direct observation and telephone interviews. Nurses, doctors and assorted HCWs reported a median of 14, 18 and 15 contact persons over one work shift, respectively. Within 1 h, we observed 3·5 episodes with 25·6 min of cumulative contact time for nurses, 2·9 episodes and 22·1 min for doctors and 5·0 episodes with 44·3 min for assorted-HCWs. In interactions with patients, nurses had multiple brief episodes of contact; doctors had fewer episodes and less cumulative contact time; assorted-HCWs had fewer contact episodes of longer durations (than for nurses and doctors). Assortative mixing occurred amongst HCWs: those of the same HCW type were the next most frequent class of contact after patients. Over 24-h, patients contacted 14 persons with 23 episodes and 314·5 min of contact time. Patient-to-patient contact episodes were rare, but a maximum of five were documented from one patient participant. 22·9% of visitors reported contact with patients other than the one they visited. Our study revealed differences in the characteristics of contacts among different HCW types and potential transmission routes from patients to others within the ward environment.

Understanding veterinarians' prescribing decisions on antibiotic dry cow therapy.

In the United Kingdom, blanket antibiotic dry cow therapy (BDCT) is commonly prescribed. An alternate strategy is selective dry cow therapy (SDCT) whereby a teat sealant is given instead of an antibiotic to cows with a low probability of infection. Switching from BDCT to SDCT can significantly reduce antibiotic use. The aims of this study were to explore how veterinarians (vets) rationalized their prescribing decisions for mammary treatments at drying off, and the barriers and motivators they perceived to implementing SDCT. Face-to-face interviews were conducted with 20 purposively recruited vets from 6 practices in England, United Kingdom. The data were analyzed qualitatively using an inductive thematic analysis. The majority of participants stated a personal preference for SDCT because it constitutes more responsible antibiotic use. On the majority of farms, the prescribing decision was taken by a senior veterinarian and BDCT was prescribed. Less experienced vets expressed a desire to be more involved in the decision-making process. The first theme, prioritizing responsible antimicrobial prescribing, encapsulated the difficulties vets expressed engaging with farmers, conflicts of interest, and vets' determination to take action. The second theme, the effect of a vet's experience on their ability to influence farmers, focused on the specific challenges faced by less experienced vets and the importance of vets being both trusted by farmers and being knowledgeable. The third theme, vets' perceptions about the risk and complexity of implementing SDCT, revealed markedly different levels of concern and fears about adverse outcomes with teat sealants versus antibiotics. The results also showed differences in perceptions about how difficult SDCT is to implement in practice. The last theme, vets' suggestions for facilitating the introduction of SDCT, was wide ranging and provided useful insight from a veterinary perspective into ways to facilitate SDCT. Initiatives that seek to alter vets' perceptions of the risks associated with switching to using SDCT are likely to prove useful in facilitating change. Our results also suggest that it is vital for senior vets to take a leading role in facilitating farms to implement SDCT. Less experienced colleagues may benefit from more help from senior vets to gain the trust of farmers and to become involved more quickly in herd-level preventive medicine. Vets must work together and take a united approach to reduce antimicrobial use.