An outbreak of hepatitis A virus infection in a secondary school in England with no undetected asymptomatic transmission among students.

In June 2019 the Health Protection Team in Yorkshire and Humber, England, was notified of cases of hepatitis A virus (HAV) infection in staff at a secondary school. Investigation revealed that an earlier case worked as a food handler in the school kitchen. Indirect transmission through food from the canteen was considered the most likely route of transmission. Cases were described according to setting of exposure. Oral fluid was obtained from students for serological testing. Environmental investigations were undertaken at settings where food handling was considered a potential transmission risk. Thirty-three confirmed cases were linked to the outbreak. All of those tested (n = 31) shared the same sequence with a HAV IB genotype. The first three cases were a household cluster and included the index case for the school. A further 19 cases (16 students, 3 staff) were associated with the school and consistent with indirect exposure to the food handler. One late onset case could not be ruled out as a secondary case within the school and resulted in vaccination of the school population. Five cases were linked to a bakery where a case from the initial household cluster worked as a food server. No concerns about hygiene standards were noted at either the school or the bakery. Oral fluid samples taken at the time of vaccination from asymptomatic students (n = 219, 11-16 years-old) showed no evidence of recent or current infection. This outbreak included household and foodborne transmission but limited (and possibly zero) person-to-person transmission among secondary school students. Where adequate hygiene exists, secondary transmission within older students may not occur.

A phase Ib dose-escalation study of the MEK inhibitor trametinib in combination with the PI3K/mTOR inhibitor GSK2126458 in patients with advanced solid tumors.

Introduction This Phase Ib trial investigated the safety, tolerability, and recommended phase 2 dose for the pan-PI3K/mTOR inhibitor, GSK2126458 (GSK458), and trametinib combination when administered to patients with advanced solid tumors. Patients and Methods Patients with advanced solid tumors received escalating doses of GSK458 (once or twice daily, and continuous or intermittent) and trametinib following a zone-based 3 + 3 design to determine the maximum tolerated dose (MTD). Assessments included monitoring for adverse events and response, and evaluating pharmacokinetic (PK) measures. Archival tissue and circulating free DNA samples were collected to assess biomarkers of response in the PI3K and RAS pathways. Results 57 patients were enrolled onto the continuous dosing cohort and 12 patients onto an intermittent BID dosing cohort. Two MTDs were established for the continuous daily dosing: 2 mg of GSK458 with 1.0 mg of trametinib or 1.0 mg of GSK458 with 1.5 mg of trametinib; no MTD was determined in the intermittent dosing cohort. The most frequent adverse events were rash (74 %) and diarrhea (61 %). Dose interruptions due to adverse events occurred in 42 % of patients. No significant PK interaction was observed. One patient achieved partial response and 12 patients had stable disease >16 weeks. Mutations in RAS/RAF/PI3K were detected in 70 % of patients, but no pattern emerged between response and mutational status. Conclusion GSK458 plus trametinib is poorly tolerated, due to skin and GI-related toxicities. Responses were minimal, despite enrichment for PI3K/RAS pathway driven tumors, which may be due to overlapping toxicities precluding sufficient dose exposure.

Patient-reported outcomes and their predictors at 2- and 3-year follow-up after immediate latissimus dorsi breast reconstruction and adjuvant treatment.

BACKGROUND: The aim of this study was to estimate the impact 2 and 3 years after surgery of implant-assisted latissimus dorsi (LDI) and autologous latissimus dorsi (ALD) flap breast reconstructions on patient-reported outcomes (PROs), and, secondarily, to determine whether baseline characteristics can predict PROs. METHODS: This was a multicentre prospective cohort study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and breast cancer module (QLQ-BR23), Functional Assessment of Cancer Therapy - Breast (FACT-B), and Hospital Anxiety and Depression Scale (HADS) PROs were completed before surgery and at 2 and 3 years after breast reconstruction. The effects of LDI and ALD, adjusted for baseline clinicodemographic characteristics, were estimated with multiple linear regressions. Effect sizes above 0·5 were considered clinically important. RESULTS: Some 206 patients (LDI 93, ALD 113) were recruited in 2007-2013; 66·5 per cent were node-negative and 34·6 per cent received radiotherapy. Women with adverse clinicopathological factors were more likely to have received radiotherapy and to undergo ALD. Patients in both surgical groups showed clinically important effects at 2 and 3 years, including improvements in emotional scales, but worse physical functioning, social well-being, body image and anxiety. Radiotherapy adversely affected social functioning at 2 years (P = 0·002). Women undergoing ALD reconstruction had significantly improved sexual functioning at 3 years (P = 0·003) relative to those who had LDI procedures, even after adjusting for case mix (P = 0·007). At 3 years, younger women experienced worse physical well-being than older women (P = 0·006), and chemotherapy was associated with worse arm symptoms (P = 0·005). CONCLUSION: Clinically important changes occurred in physical functioning, breast symptoms, body image and psychological distress. These results will guide selections of key PRO domains and sample-size calculation of future studies.

Randomised comparison of the effectiveness of the laryngeal mask airway supreme, i-gel and current practice in the initial airway management of out of hospital cardiac arrest: a feasibility study.

BACKGROUND: The best initial approach to advanced airway management during out of hospital cardiac arrest (OHCA) is unknown. The traditional role of tracheal intubation has been challenged by the introduction of supraglottic airway devices (SGAs), but there is contradictory evidence from observational studies. We assessed the feasibility of a cluster-randomized trial to compare the i-gel SGA vs the laryngeal mask airway supreme (LMAS) vs current practice during OHCA. METHODS: We conducted a cluster-randomized trial in a single ambulance service in England, with individual paramedics as the unit of randomization. Consenting paramedics were randomized to use either the i-gel or the LMAS or usual practice for all patients with non-traumatic adult OHCA, that they attended over a 12-month period. The primary outcome was study feasibility, including paramedic and patient recruitment and protocol adherence. Secondary outcomes included survival to hospital discharge and 90 days. RESULTS: Of the 535 paramedics approached, 184 consented and 171 attended study training. Each paramedic attended between 0 and 11 patients (median 3; interquartile range 2-5). We recruited 615 patients at a constant rate, although the LMAS arm was suspended in the final two months following three adverse incidents. The study protocol was adhered to in 80% of patients. Patient characteristics were similar in the three study arms, and there were no differences in secondary outcomes. CONCLUSION: We have shown that a prospective trial of alternative airway management strategies in OHCA, cluster randomized by paramedic, is feasible. CLINICAL TRIAL REGISTRATION: Registered on the International Standard Randomised Controlled Trial Registry ( ISRCTN: 18528625).

Optimizing MRI of small joints and extremities.

Obtaining optimal images of small joints using magnetic resonance imaging (MRI) can be technically challenging. The aim of this review is to outline the practical aspects of MRI of small joints, with reference to the underlying physical principles. Although the most important contribution to successful imaging of small joints comes from the magnet field strength and design of the receiver coil, there are a number of factors to balance including the signal-to-noise ratio, image resolution, and acquisition times. We discuss strategies to minimize artefacts from movement, inhomogeneity, chemical shift, and fat suppression. As with all MRI, each strategy comes at a price, but the benefits and costs of each approach can be fine-tuned to each combination of joint, receiver coil, and MRI machine.

Ovarian and placental morphology and endocrine functions in the pregnant giraffe (Giraffa camelopardalis).

Gross, histological and immunocytochemical examinations carried out on maternal and fetal reproductive tissues from two pregnant giraffes at an estimated 8 and 13.5 months of gestation (term=15 months) revealed a typically ruminant macrocotyledonary placenta with binucleate trophoblast cells scattered sparsely in the placentome where they stained intensely with a prolactin antiserum. Binucleate cells were present in greater numbers in the intercotyledonary allantochorion where they did not stain for prolactin whereas the uninucleate trophoblast still did. A single large corpus luteum of pregnancy and several small luteinised follicles were present in the maternal ovaries while the fetal ovaries at 13.5 months gestation showed an assortment of enlarging antral follicles and partially and completely lutenised follicles, the granulosa and luteal cells of which stained positively for 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17,20 lyase, prolactin, progesterone receptor and androgen receptor, but negatively for aromatase. The uninucleate trophoblast of the placentome and intercotyledonary allantochorion, the epithelium of the maternal endometrial glands, the seminiferous epithelium in the fetal testis at 8 months of gestation and the zonae fasciculata and reticularis of the fetal adrenal at 13.5 months also stained positively for 3ß-HSD and negatively for aromatase. Endocrinologically, it appears that the giraffe placenta is more similar to that of the sheep than the cow with a placental lactogen as the likely driver of the considerable degree of luteinisation seen in both the maternal and the fetal ovaries.

Randomized clinical trial on the effect of fibrin sealant on latissimus dorsi donor-site seroma formation after breast reconstruction.

BACKGROUND: Latissimus dorsi (LD) flap procedures comprise 50 per cent of breast reconstructions in the UK. They are frequently complicated by seroma formation. Fibrin sealants may reduce seroma volumes at the donor site. The aim was to investigate the effect of fibrin sealant (Tisseel(®)) on total seroma volumes from the breast, axilla and back (donor site) after LD breast reconstruction. Secondary outcomes were specific back seroma volumes together with incidence and severity of wound complications. METHODS: Consecutive women undergoing implant-assisted or extended autologous LD flap reconstruction were randomized to either standard care or application of fibrin sealant to the donor-site chest wall. All participants were blinded for the study duration but assessors were only partially blinded. Non-parametric methods were used for analysis. RESULTS: A total of 107 women were included (sealant 54, control 53). Overall back seroma volumes were high, with no significant differences between control and sealant groups over 3 months. Fibrin sealant failed to reduce in situ back drainage volumes in the 10 days after surgery, and did not affect the rate or volume of seromas following drain removal. CONCLUSION: This randomized study, which was powered for size effect, failed to show any benefit from fibrin sealant in minimizing back seromas after LD procedures.

Use of expiratory CT pulmonary angiography to reduce inspiration and breath-hold associated artefact: contrast dynamics and implications for scan protocol.

AIM: To investigate the effects of scanning in expiration during computed tomography pulmonary angiography (CTPA). MATERIALS AND METHODS: One hundred and eighty-one consecutive expiratory CTPA examinations were compared with 145 inspiratory CTPA examinations performed using a standardized protocol through assessment of attenuation seen in the cardiac chambers, pulmonary artery (PA), and ascending aorta. RESULTS: Expiratory scans showed greater attenuation at the pulmonary trunk, right PA, left PA, lobar and segmental PAs (p<0.05). Expiratory scans showed a lower incidence of transient contrast medium interruption (p<0.001) and generalized unsatisfactory PA opacification (p<0.05). Scans with generalized low PA attenuation had lower attenuation in the right ventricle, left heart, and ascending aorta (p<0.001) suggesting that contrast medium delivery or dilution prior to contrast medium entry into the PA is responsible. Expiratory scans showed lower quality scores (p<0.001) for depiction of lung parenchyma. CONCLUSION: Expiratory scanning could be used as an optimal protocol for dedicated PA imaging. However, it suffers from inferior parenchymal imaging and should probably be reserved for failed inspiratory breath-hold CTPA.

Standardizing the intensity of upper limb treatment in rehabilitation medicine.

OBJECTIVE: To describe a treatment protocol for the upper limb that standardizes intensity of therapy input regardless of the severity of presentation. DESIGN: The protocol is described (Part 1) and feasibility and effect explored (Part 2). SUBJECTS: Participants (n = 11) had a single ischaemic stroke in the middle cerebral artery territory more than one year previously, and had residual weakness of the hand with some extension present at the wrist and the ability to grasp. INTERVENTIONS: Following two baseline assessments, participants attended therapy for 1 hour a day for 10 consecutive working days. Treatment consisted of a combination of strength and functional task training. Outcomes were measured immediately after training, at one month and three months. OUTCOME MEASURES: Intensity was measured with Borg Rating of Perceived Exertion. Secondary outcome measures included Action Research Arm Test (ARAT), nine-hole peg test, and Goal Attainment Scale. RESULTS: Borg scores indicated that the level of intensity was appropriate and similar across all participants despite individual differences in the severity of their initial presentation (median (interquartile range) = 14 (13-15)). The mean ARAT score significantly increased by 6.8 points (chi(2)(3) = 15.618, P<0.001), and was maintained at three-month follow-up (z = - 2.384, P = 0.016). The nine-hole peg test also showed a main effect of time and 88% of goals set were achieved. CONCLUSIONS: The physiotherapy protocol standardized intensity of treatment by grading exercise and task-related practice according to the person's residual ability, rather than simply standardizing treatment times. It was feasible and well tolerated in this group.

Placentation and hormonal maintenance of pregnancy in the impala (Aepyceros melampus).

INTRODUCTION: The impala is a widely distributed African ungulate. Detailed studies of the placenta and ovaries in impala undertaken in the 1970s did not address the endocrine functions of the placenta. METHODS: The uteri of 25 pregnant impala estimated to be between 49 and 113 days of the 190 day gestation were examined grossly, histologically and immunohistochemically. RESULTS: A single corpus luteum was present in either maternal ovary but the conceptus was always situated in the right uterine horn. The fetal membranes extended to the tips of both uterine horns. The amnion was in intimate contact with, but not fused to, the allantochorion. Placentation was typically ruminant with fetal macrocotyledons attached to the rows of maternal caruncles. The fetal villi were highly branched, especially in the centre of each placentome where the attenuated maternal epithelium lining the placental crypts was absent in some places. Both the corpus luteum and the uninucleate trophoblast cells of the interplacentomal allantochorion stained strongly for 3-ß hydroxysteroid dehydrogenase, and progestagen concentrations in allantoic and amniotic fluids increased significantly as gestation progressed, with a tendency to do likewise in maternal serum. Binucleate trophoblast cells stained positively for bovine placental lactogen, but neither the placenta nor the maternal corpus luteum showed evidence of oestrogen synthesis. DISCUSSION: Despite exhibiting the same basic type of placentation, both the gross and histological structure of the impala placenta, along with its immunohistochemical properties, demonstrates that great variation exists across ruminant placentas.

The SPaCE diagnostic: a pilot study to test the accuracy of a novel point of care sensor for point of care detection of burn wound infection.

BACKGROUND: Wound infection in burn patients is common and has an impact on outcomes. There is no objective method to diagnose infection at point of care (PoC). Early diagnosis prevents progression to sepsis. Diagnostic subjectivity supports over-diagnosis, unnecessary hospitalization, and antibiotic overuse. AIM: This pilot study aimed to investigate the accuracy of a novel PoC wound infection diagnostic in burn patients. METHODS: We produced, and in vitro tested, a PoC diagnostic for early wound infection diagnosis. The prototype SPaCE diagnostic uses a patented lipid vesicle suspension into which a clinical swab is placed. The diagnostic delivers a colour-response to Staphylococcus aureus, Pseudomonas aeruginosa, Candida species and Enterococcus faecalis at toxin release. A pilot clinical diagnostic accuracy study was undertaken. The reference standard was a retrospective decision made by an expert clinical panel using routinely available data. FINDINGS: Data was available from 33 of 34 patients. Of these, 52% were considered to have a wound infection, 42% not, and two (6%) were equivocal. The diagnostic results showed 24% were infected, 42% were not and 33% produced intermediate results. Agreement between clinical judgement and diagnostic result, assessed using a weighted Kappa, was 0.591 suggesting moderate agreement. If the intermediate results were excluded, 22 sets of data with definitive results achieved a Kappa statistic of 0.81 suggesting 'almost perfect' agreement. Sensitivity and specificity were 57% (8/14) and 71% (12/17), respectively. CONCLUSION: This pilot study provided evidence that the SPaCE diagnostic could provide valuable and timely data to support clinical decision-making at PoC for wound infection.

Health-related quality of life assessment after breast reconstruction.

BACKGROUND: Health-related quality of life (HRQL) is an important outcome following breast reconstruction. This study evaluated current methods of HRQL assessment in patients undergoing latissimus dorsi breast reconstruction, hypothesizing that early surgical morbidity would be reflected by poorer HRQL scores. METHODS: Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and breast module (QLQ-BR23), the Functional Assessment of Cancer Therapy (FACT) general measure, and breast module and arm subscale (FACT-B + 4), and the Body Image Scale and Hospital Anxiety and Depression Scale (HADS) 3 months after surgery. They also reported additional HRQL problems not included in the questionnaires. HRQL scores were compared between patients with and without early surgical morbidity. RESULTS: Sixty women completed the questionnaires, of whom 25 (42 per cent) experienced complications. All EORTC and FACT subscale and HADS scores were similar in patients with or without morbidity. Women with complications were twice as likely to report feeling less feminine and dissatisfied with the appearance of their scar than those without problems. Thirty-two women (53 per cent) complained of problems not covered by the questionnaires, most commonly donor-site morbidity. CONCLUSION: Existing HRQL instruments are not sufficiently sensitive to detect clinically relevant problems following breast reconstruction.

Trends in yield and effects of screening intervals during 17 years of a large UK community-based diabetic retinopathy screening programme.

AIMS: To describe changes in risk profiles and yield in a screening programme and to investigate relationships between retinopathy prevalence, screening interval and risk factors. METHODS: We analysed a population of predominantly Type 2 diabetic patients, managed in general practice, and screened between 1990 and 2006, with up to 17 years' follow-up and up to 14 screening episodes each. We investigated associations between referable or sight-threatening diabetic retinopathy (STDR), screening interval and frequency of repeated screening, whilst adjusting for age, duration and treatment of diabetes, hypertension treatment and period. RESULTS: Of 63 622 screening episodes among 20 788 people, 16 094 (25%) identified any retinopathy, 3136 (4.9%) identified referable retinopathy and 384 (0.60%) identified STDR. The prevalence of screening-detected STDR decreased by 91%, from 1.7% in 1991-1993 to 0.16% in 2006. The prevalence of referable retinopathy increased from 2.0% in 1991-1993 to 6.7% in 1998-2001, then decreased to 4.7% in 2006. Compared with screening intervals of 12-18 months, screening intervals of 19-24 months were not associated with increased risk of referable retinopathy [adjusted odds ratio 0.93, 94% confidence interval (CI) 0.82-1.05], but screening intervals of more than 24 months were associated with increased risk (odds ratio 1.56, 95% CI 1.41-1.75). Screening intervals of < 12 months were associated with high risks of referable retinopathy and STDR. CONCLUSIONS: Over time the risk of late diagnosis of STDR decreased, possibly attributable to earlier diagnosis of less severe retinopathy, decreasing risk factors and systematic screening. Screening intervals of up to 24 months should be considered for lower risk patients.

Differing effects of intracortical circuits on plasticity.

Practice of a motor task leads to an increase in amplitude of motor-evoked potentials (MEP) in the exercised muscle. This is termed practice-dependent plasticity, and is abolished by the NMDA antagonist dextromethorphan and the GABA(A) agonist lorazepam. Here, we sought to determine whether specific subtypes of GABA(A) circuits are responsible for this effect by comparing the action of the non-selective agonist, lorazepam with that of the selective GABA(A)-alpha(1) receptor agonist, zolpidem. In seven healthy subjects, transcranial magnetic stimulation (TMS) was used to quantify changes in amplitude of MEP after practice of a ballistic motor task. In addition we measured how the same drugs affected MEP amplitudes and the excitability of a number of cortical inhibitory circuits [short-interval intracortical inhibition (SICI), short-interval afferent inhibition (SAI) and long-interval intracortical inhibition]. This allowed us to explore correlations between drugs effects in measures of cortical excitability and practice-dependent plasticity of MEP amplitudes. As previously reported, lorazepam increased SICI and decreased SAI, while zolpidem only decreased SAI. The new findings were that practice-dependent plasticity of MEPs was impaired by lorazepam but not zolpidem, and that this was negatively correlated with lorazepam-induced changes in SICI but not SAI. This suggests that the intracortical circuits involved in SICI (and not neurons expressing GABA(A)-alpha(1) receptor subunits that are implicated in SAI) may be involved in controlling the amount of practice-dependent MEP plasticity.

Lateropulsion, pushing and verticality perception in hemisphere stroke: a causal relationship?

The relationships between perception of verticality by different sensory modalities, lateropulsion and pushing behaviour and lesion location were investigated in 86 patients with a first stroke. Participants sat restrained in a drum-like framework facing along the axis of rotation. They gave estimates of their subjective postural vertical by signalling the point of feeling upright during slow drum rotation which tilted them rightwards-leftwards. The subjective visual vertical was indicated by setting a line to upright on a computer screen. The haptic vertical was assessed in darkness by manually setting a rod to the upright. Normal estimates ranged from -2.5 degrees to 2.5 degrees for visual vertical and postural vertical, and from -4.5 degrees to 4.5 degrees for haptic vertical. Of six patients with brainstem stroke and ipsilesional lateropulsion only one had an abnormal ipsilesional postural vertical tilt (6 degrees ); six had an ipsilesional visual vertical tilt (13 +/-.4 degrees ); two had ipsilesional haptic vertical tilts of 6 degrees . In 80 patients with a hemisphere stroke (35 with contralesional lateropulsion including 6 'pushers'), 34 had an abnormal contralesional postural vertical tilt (average -8.5 +/- 4.7 degrees ), 44 had contralesional visual vertical tilts (average -7 +/- 3.2 degrees ) and 26 patients had contralesional haptic vertical tilts (-7.8 +/- 2.8 degrees ); none had ipsilesional haptic vertical or postural vertical tilts. Twenty-one (26%) showed no tilt of any modality, 41 (52%) one or two abnormal modality(ies) and 18 (22%) a transmodal contralesional tilt (i.e. PV + VV + HV). Postural vertical was more tilted in right than in left hemisphere strokes and specifically biased by damage to neural circuits centred around the primary somatosensory cortex and thalamus. This shows that thalamo-parietal projections have a functional role in the processing of the somaesthetic graviceptive information. Tilts of the postural vertical were more closely related to postural disorders than tilts of the visual vertical. All patients with a transmodal tilt showed a severe lateropulsion and 17/18 a right hemisphere stroke. This indicates that the right hemisphere plays a key role in the elaboration of an internal model of verticality, and in the control of body orientation with respect to gravity. Patients with a 'pushing' behaviour showed a transmodal tilt of verticality perception and a severe postural vertical tilt. We suggest that pushing is a postural behaviour that leads patients to align their erect posture with an erroneous reference of verticality.

A double-blind randomised clinical trial of the treatment of otitis externa using topical steroid alone versus topical steroid-antibiotic therapy.

The objective of the study was to determine if the addition of topical antibiotic increases the efficacy of topical steroid in controlling otitis externa. A double-blind randomised controlled trial was performed from February 2003 to April 2005 in an otolaryngology emergency clinic (acute urban teaching hospital) in the United Kingdom. Patients were followed up for 2 weeks. Forty-five adults with otitis externa based on the presence of oedema, discharge or debris in the outer ear canal were recruited. The patients were randomised to one of the two treatment groups, namely using betamethasone sodium phosphate 0.1% (Vista-Methasone) or betamethasone sodium phosphate 0.1% with neomycin sulphate 0.5% (Vista-Methasone N), and were instructed to use the trial medication at three drops three times a day for 2 weeks. Subjects' visual analogue symptom scores (blockage, pain, discharge, and itching) for otitis externa pre-treatment (day 0) and post-treatment (day 15), percentage changes in visual analogue symptom scores as a result of treatment, proportion of patients whose symptom scores failed to improve or deteriorated on treatment were analysed. The two experimental arms demonstrated statistically similar presenting symptom scores at recruitment (mean symptom scores of 19.2 for betamethasone group and 28.7 for betamethasone-neomycin group). The mean symptom score change in response to treatment was 82.8 and 47.8% in the betamethasone-neomycin and betamethasone-alone groups, respectively. There was no statistically significant difference between the groups in median percentage symptom score change in response to treatment. All patients in the betamethasone-neomycin group showed symptom improvement but in the betamethasone alone group, five patients got worse (Fishers exact, P = 0.05). Topical antibiotic-steroid combination therapy is superior to steroid-alone treatment for symptomatic control of otitis externa.

The peripheral nervous system and the perception of verticality.

Orientation of the body with respect to gravity is based on integration of visual, vestibular and somatosensory signals. Here, we investigated the subjective postural vertical (SPV) and visual vertical (SVV) in three patients with bilateral somatosensory deafferentation and a group of age-matched normal subjects. Our hypothesis was that the patients with bilateral somatosensory deafferentation may show tilt induced bias in the construction of their SPV, with a normal SVV. Patient 1 had a severe Guillain Barré syndrome and almost complete absence of peripheral sensation, the two other patients had a thoracic spinal injury with a sensory loss from T6-7 down. On initial testing, compared with normal subjects and the patients with spinal injury, Patient 1 had a significant bias in SPV towards the side of a preceding tilt in both directions. Several months later, after significant improvement of sensation, this tilt-induced bias in SPV had resolved completely. In addition, Patient 1 had a significantly enlarged "cone of verticality", which did not change following improvement in peripheral sensation, reflecting persisting disturbance in the perception of body verticality. In the two patients with spinal injury, bias towards the side of a preceding tilt was not significant. These findings confirm the importance of somatosensory input from the trunk to the perception of SPV in the seated position.

A pilot randomised controlled trial investigating a mindfulness-based stress reduction (MBSR) intervention in individuals with pulmonary arterial hypertension (PAH): the PATHWAYS study.

BACKGROUND: Pulmonary arterial hypertension (PAH) is an uncommon condition with progressive heart failure and premature death. Treatment costs up to £120,000 per patient per year, and the psychological burden of PAH is substantial. Mindfulness-based stress reduction (MBSR) is an intervention with the potential to reduce this burden, but to date, it has not been applied to people with pulmonary hypertension. We wished to determine whether a trial of MBSR for people with PAH would be feasible. METHODS: A customised gentle MBSR programme of eight sessions was developed for people with physical disability due to PAH, and they were randomised to group-based MBSR or treatment as usual. The completeness of outcome measures including Beck Anxiety Index, Beck Depression Inventory and standard physical assessment at 3 months after randomisation were recorded. Health care utilisation was measured. Attendance at the sessions and the costs involved in delivering the intervention were assessed. Semi-structured interviews were conducted to explore the acceptability of the MBSR intervention and when appropriate the reasons for trial non-participation. RESULTS: Fifty-two patients were recruited, but only 34 were randomised due to patients finding it difficult to travel to sessions. Twenty-two completed all questionnaires and attended all clinics, both routine and additional in order to collect outcomes measures. The MSBR sessions were delivered in Bristol, Cardiff and London, costing, on average, between £2234 (Cardiff) and £4128 (London) per patient to deliver. Attendance at each session averaged between two patients in Bristol and Cardiff and three in London. For those receiving treatment as usual, clinician blinding was achievable. Interviews revealed that people who attended MBSR found it interesting and helpful in managing their symptoms and minimising the psychological component of their disease. CONCLUSIONS: We found that attendance at group MBSR was poor in people with chronic PAH within the context of a trial. Achieving better MBSR intervention attendance or use of an Internet-based programme might maximise the benefit of MBSR.

Knowledge, attitudes, and practices about homelessness and willingness-to-pay for housing-first across 8 European countries: a survey protocol.

BACKGROUND: Most European countries report rising numbers of people experiencing homelessness. For those with mental disorders, interventions are centered on achieving mental health and drug rehabilitation alongside housing readiness, often to the detriment of access to housing. Notwithstanding, more European countries are investing in a new model, Housing First (HF), which postulates immediate access to permanent housing with no initial requirements for treatment. While results of the European HF programs are published on individual-level data, little is known about the opinions of the general population about homelessness and the societal value of the HF model, which can represent barriers to the model's dissemination. Therefore, we present the protocol of a study designed for the following objectives: 1) to explore the knowledge, attitudes, and practices (KAP) about homelessness within the general population of 8 European countries, 2) to assess the valuation of the HF model by European citizens, and 3) to estimate the lifetime prevalence of homelessness in the targeted countries. METHODS: A telephone survey was conducted from March to December 2017 among adults selected from opt-in panels from France, Ireland, Italy, the Netherlands, Portugal, Spain, Poland, and Sweden. A total sample of 5600 interviews was expected, with 700 per country. The interviews included three sections: first, the KAP about homelessness; second, the valuation of the HF model by measuring a respondent's willingness-to-pay (WTP) through the contingent valuation method; and third, an assessment of the lifetime prevalence of homelessness among the general population. Descriptive analyses and comparisons between countries will be conducted. KAP indicators will be created and their psychometric properties assessed. Determinants of WTP will be assessed through regression models. DISCUSSION: This survey will highlight Europeans' views of homelessness, especially their level of tolerance towards homelessness, potential misconceptions and the most important barriers for the implementation of the HF model. Additionally, the results on the valuation of the HF model by citizens could be instrumental for key stakeholders in understanding the level of support from the general population. Ethics approval has been obtained from the Aix-Marseille University Ethics Committee (n° 2016-01-02-01) for this study, which is part of HOME_EU: Reversing Homelessness in Europe H2O20-SC6-REVINEQUAL-2016/GA726997.

Systematic review of the impact of breast-conserving surgery on cancer outcomes of multiple ipsilateral breast cancers.

BACKGROUND: The clinical effectiveness of treating ipsilateral multifocal (MF) and multicentric (MC) breast cancers using breast-conserving surgery (BCS) compared with the standard of mastectomy is uncertain. Inconsistencies relate to definitions, incidence, staging and intertumoral heterogeneity. The primary aim of this systematic review was to compare clinical outcomes after BCS versus mastectomy for MF and MC cancers, collectively defined as multiple ipsilateral breast cancers (MIBC). METHODS: Comprehensive electronic searches were undertaken to identify complete papers published in English between May 1988 and July 2015, primarily comparing clinical outcomes of BCS and mastectomy for MIBC. All study designs were included, and studies were appraised critically using the Newcastle-Ottawa Scale. The characteristics and results of identified studies were summarized. RESULTS: Twenty-four retrospective studies were included in the review: 17 comparative studies and seven case series. They included 3537 women with MIBC undergoing BCS; breast cancers were defined as MF in 2677 women, MC in 292, and reported as MIBC in 568. Six studies evaluated MIBC treated by BCS or mastectomy, with locoregional recurrence (LRR) rates of 2-23 per cent after BCS at median follow-up of 59·5 (i.q.r. 56-81) months. BCS and mastectomy showed apparently equivalent rates of LRR (risk ratio 0·94, 95 per cent c.i. 0·65 to 1·36). Thirteen studies compared BCS in women with MIBC versus those with unifocal cancers, reporting LRR rates of 2-40 per cent after BCS at a median follow-up of 64 (i.q.r. 57-73) months. One high-quality study reported 10-year actuarial LRR rates of 5·5 per cent for BCS in 300 women versus 6·5 per cent for mastectomy among 887 women. CONCLUSION: The available studies were mainly of moderate quality, historical and underpowered, with limited follow-up and biased case selection favouring BCS rather than mastectomy for low-risk patients. The evidence was inconclusive, weakening support for the St Gallen consensus and supporting a future randomized trial.