Use of the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity ('P-POSSUM') to predict morbidity in patients undergoing surgery with reconstruction for temporal bone malignancy.

OBJECTIVE: The Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity ('P-POSSUM') is a two-part scoring system that includes a physiological assessment and a measure of operative severity. This study sought to determine whether risk estimates for this scoring system could be used in major head and neck reconstructive surgery. METHOD: A retrospective review was performed of patients undergoing resection for a temporal bone malignancy in a single head and neck centre in Dublin, Ireland, from 2002 to 2021. RESULTS: The mean ± standard deviation morbidity estimate calculated using the scoring system was 47.6 per cent ± 19.5 per cent. The actual rate of complications was 47 per cent. The optimal cut-off for the scoring system was calculated using the Youden index from the receiver operating characteristic curve, which was 40.5 per cent in this case. CONCLUSION: The study indicates that the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity is a useful tool for predicting morbidity risk in patients undergoing head and neck resection with reconstruction for temporal bone malignancies.

Enabling uptake and sustainability of supervision roles by women GPs in Australia: a narrative analysis of interviews.

BACKGROUND: Worldwide, the proportion of women entering careers in medicine is increasing. To ensure diversity and capacity in the general practice ("GP") supervision workforce, a greater understanding from the perspective of women GPs engaged in or considering the clinical supervision of trainee doctors is important. This narrative inquiry aims to explore the uptake and sustainability of supervision roles for women GPs in the Australian context. METHODS: Qualitative interviews with Australian women GPs were conducted between July and September 2021. Women GPs were selected to represent a range of demographics, practice contexts, and supervision experience to promote broad perspectives. Narrative analysis drew on participant perspectives, allowing emergent stories to be explored using story arcs based on the characters, settings, problems, actions, and resolutions. These stories were evaluated by a broad research team and a high level of agreement of the final narratives and counter-narratives was achieved. RESULTS: Of the 25 women who enrolled, 17 completed interviews. Six narratives emerged, including: power and control, pay, time, other life commitments, quality of supervision, and supervisor identity. These represented significant intersecting issues with the potential to impact the uptake and sustainability of supervision by women GPs. Some women GPs reported a lack of agency to make decisions about their role in supervision and were not remunerated for teaching. Uptake and sustainability of supervision was constrained by other life commitments, which could be buffered by team-sharing arrangements and a supportive practice. Although adding a burden of time atop their complex and sensitive consultations, women GPs were committed to being available to registrars and supervising at a high standard. To foster high quality supervision, women GPs were interested in up-skilling resources, building experience and harnessing support networks. Women sensed imposter syndrome when negotiating a supervisor identity, which could be managed by explicitly valuing their contribution. CONCLUSION: The findings can inform the development of more specific resources, supports and structures to enable women GPs in Australia to uptake and sustain the supervision of trainee doctors at a level they find both acceptable and rewarding.

The Potential Impact and Usability of the Eighth Edition TNM Staging Classification in Oral Cavity Cancer.

AIMS: In the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: OSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN-), pathological node-positive without ENE (pN+_pENE-) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison. RESULTS: In total, 478 patients were evaluated: 173 pN-; 159 pN+_pENE-; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P < 0.001). Distant control was 97%, 87%, 68% (P < 0.001) and overall survival was 75%, 53% and 39% (P < 0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE- (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE- (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b. CONCLUSIONS: When eighth edition staging was applied, stage migration across the N2-3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.

A study to assess smoking habits and smoking exposure in sportspeople.

BACKGROUND: Tobacco smoking is a leading public health concern and is the most preventable cause of morbidity and mortality worldwide. Sportspeople are no exception and those who smoke are predisposed to the same hazardous health effects as the general public, in addition to the potential effects it may have on their sporting performance. AIM: We aimed to ascertain the prevalence of tobacco consumption in a sporting population. We also endeavoured to quantify the use of electronic cigarettes (e-cigarettes) and assess exposure to passive smoking. DESIGN: Observational study. METHODS: A web-based e-questionnaire was distributed to participants from various sports across Ireland between November 2017 and January 2018, and data were analysed using SPSS. RESULTS: A total of 546 sportspeople completed the survey with more than twice as many male respondents. Of whom, 16% of participants were current smokers, with males significantly more likely to smoke (P < 0.001), 26% of rugby players were current smokers which was significantly higher when compared with other sports (P < 0.01), 10% of all participants were exposed to second-hand smoke for more than 1 h per day and 2% of all participants were current users of e-cigarettes. CONCLUSION: The prevalence of smoking in our study population was higher than other literature reports. Further studies are essential to evaluate the potential negative effects this may be having on sporting performance, career progression and indeed injury occurrence/rehabilitation. It is imperative to address the matter of smoking in athletes, not only for public health concerns but also considering they are important role models in our society.

Phase I trial of alpelisib in combination with concurrent cisplatin-based chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Deregulation of the PI3K signalling pathway is frequent in squamous cell carcinoma of the head and neck (SCCHN) and may be implicated in radioresistance. We report on the results from a phase I 3 + 3 dose escalation study of alpelisib, a class I α-specific PI3K inhibitor in combination with concurrent cisplatin-based chemoradiation (CRT) in patients with locoregionally advanced SCCHN (LA-SCCHN). METHODS: Eligible patients had previously untreated LA-SCCHN and were candidates for CRT. The primary objective was to evaluate safety and determine the recommended phase II dose (RP2D). Alpelisib was given orally once daily at two dose levels: 200 mg and 250 mg. CRT consisted of cisplatin 100 mg/m2 IV every three weeks and standard fractionation radiotherapy (IMRT) 70 Gy in 35 fractions. RESULTS: Nine patients were enrolled (six alpelisib 200 mg, three 250 mg). Oropharynx was the primary site in all patients (seven p16-positive; five T1-2N2M0, four T3-4N2-3M0 [AJCC 7th edition]). All patients completed CRT within seven weeks. Grade 3 alpelisib-related toxicities occurred in four patients. No dose-limiting toxicity (DLT) was observed at 200 mg among three DLT-evaluable patients. Two of two DLT-evaluable patients treated at 250 mg experienced DLTs (inability to complete ≥75% alpelisib secondary to radiation dermatitis and febrile neutropenia). Thus, RP2D was declared at 200 mg. After median follow-up of 39.7 months, two patients developed pulmonary metastases despite locoregional control. Three-year overall survival was 77.8% (95% CI 36.5%-93.9%). CONCLUSION: Alpelisib at 200 mg has a manageable safety profile in combination with cisplatin-based CRT in LA-SCCHN.

Development and validation of a clinical prediction-score model for distant metastases in major salivary gland carcinoma.

BACKGROUND: The most common pattern of failure in major salivary gland carcinoma (SGC) is development of distant metastases (DMs). The objective of this study was to develop and validate a prediction score for DM in SGC. PATIENTS AND METHODS: Patients with SGC treated curatively at four tertiary cancer centers were divided into discovery (n = 619) and validation cohorts (n = 416). Multivariable analysis using competing risk regression was used to identify predictors of DM in the discovery cohort and create a prediction score of DM; the optimal score cut-off was determined using a minimal P value approach. The prediction score was subsequently evaluated in the validation cohort. The cumulative incidence and Kaplan-Meier methods were used to analyze DM and overall survival (OS), respectively. RESULTS: In the discovery cohort, DM predictors (risk coefficient) were: positive margin (0.6), pT3-4 (0.7), pN+ (0.7), lymphovascular invasion (0.8), and high-risk histology (1.2). High DM-risk SGC was defined by sum of coefficients greater than two. In the discovery cohort, the 5-year incidence of DM for high- versus low-risk SGC was 50% versus 8% (P < 0.01); this was similar in the validation cohort (44% versus 4%; P < 0.01). In the pooled cohorts, this model performed similarly in predicting distant-only failure (40% versus 6%, P < 0.01) and late (>2 years post surgery) DM (22% versus 4%; P < 0.01). Patients with high-risk SGC had an increased incidence of DM in the subgroup receiving postoperative radiation therapy (46% versus 8%; P < 0.01). The 5-year OS for high- versus low-risk SGC was 48% versus 92% (P < 0.01). CONCLUSION: This validated prediction-score model may be used to identify SGC patients at increased risk for DM and select those who may benefit from prospective evaluation of treatment intensification and/or surveillance strategies.

The impact of behavioural skills training on the knowledge, skills and well-being of front line staff in the intellectual disability sector: a clustered randomised control trial.

BACKGROUND: Staff with varying backgrounds and educational qualifications can be effectively trained to implement procedures in line with evidence-based practice. Behavioural skills training (BST) is a competency-based training model used to effectively educate a broad selection of professionals, including front line staff, in a range of work-related skills. However, BST has yet to be evaluated in a large group-based experiment. METHODS: This study involved a parallel cluster randomised control trial. Six service sites, with a total of 54 participants, were randomised to the intervention condition using the 'coin toss' method. The intervention condition used BST to coach intellectual disability staff in reinforcement, systematic prompting, functional communication training and task analysis. Six service sites, with a total of 50 participants, were also randomised to a control condition in which generalised training in behavioural interventions was restricted. Recruited service sites were randomly assigned to the intervention condition (N = 6, n = 54) or the control condition (N = 6, n = 50) at one point in time, immediately after recruitment and before baseline testing took place. Allocations were stratified by service type (residential or day) and geographical region. One member of the research team allocated service sites using the 'coin toss' method, and another member, blind to the allocations, decided which experimental arm would receive the intervention and which would be designated as control. It was not possible to mask the intervention from participants, but they were recruited prior to randomisation. RESULTS: Participants in the intervention condition demonstrated statistically significant improvements in their knowledge scores over the study period. Participants in the control condition showed no change or a statistically significant decrease in their knowledge scores. No statistically significant changes to well-being were observed for either group. There was clear evidence of knowledge maintenance, as well as skill acquisition and subsequent generalisation to the workplace environment, among participants in the intervention condition. Participants also evaluated the BST intervention positively. CONCLUSIONS: Results support BST as a method for disseminating evidence-based practice to front line staff working with adults with intellectual and developmental disabilities.

Identification and validation of novel microenvironment-based immune molecular subgroups of head and neck squamous cell carcinoma: implications for immunotherapy.

Background: Targeting the immune checkpoint pathway has demonstrated antitumor cytotoxicity in treatment-refractory head and neck squamous cell carcinoma (HNSC). To understand the molecular mechanisms underpinning its antitumor response, we characterized the immune landscape of HNSC by their tumor and stromal compartments to identify novel immune molecular subgroups. Patients and methods: A training cohort of 522 HNSC samples from the Cancer Genome Atlas profiled by RNA sequencing was analyzed. We separated gene expression patterns from tumor, stromal, and immune cell gene using a non-negative matrix factorization algorithm. We correlated the expression patterns with a set of immune-related gene signatures, potential immune biomarkers, and clinicopathological features. Six independent datasets containing 838 HNSC samples were used for validation. Results: Approximately 40% of HNSCs in the cohort (211/522) were identified to show enriched inflammatory response, enhanced cytolytic activity, and active interferon-γ signaling (all, P < 0.001). We named this new molecular class of tumors the Immune Class. Then we found it contained two distinct microenvironment-based subtypes, characterized by markers of active or exhausted immune response. The Exhausted Immune Class was characterized by enrichment of activated stroma and anti-inflammatory M2 macrophage signatures, WNT/transforming growth factor-ß signaling pathway activation and poor survival (all, P < 0.05). An enriched proinflammatory M1 macrophage signature, enhanced cytolytic activity, abundant tumor-infiltrating lymphocytes, high human papillomavirus (HPV) infection, and favorable prognosis were associated with Active Immune Class (all, P < 0.05). The robustness of these immune molecular subgroups was verified in the validation cohorts, and Active Immune Class showed potential response to programmed cell death-1 blockade (P = 0.01). Conclusions: This study revealed a novel Immune Class in HNSC; two subclasses characterized by active or exhausted immune responses were also identified. These findings provide new insights into tailoring immunotherapeutic strategies for different HNSC subgroups.

Radiologic-Pathologic Correlation of Tumor Thickness and Its Prognostic Importance in Squamous Cell Carcinoma of the Oral Cavity: Implications for the Eighth Edition Tumor, Node, Metastasis Classification.

BACKGROUND AND PURPOSE: Addressing the performance of an imaging-based parameter compared to a "gold standard" pathologic measurement is essential to achieve accurate clinical T-classification. Our aim was to determine the radiologic-pathologic tumor thickness correlation and its prognostic value in oral squamous cell carcinoma. MATERIALS AND METHODS: All pathologic T1-T3 (seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer) oral squamous cell carcinomas diagnosed between 2010 and 2015 were reviewed. Radiologic tumor thickness was measured on preoperative CT or MR imaging blinded to pathology. The radiologic-pathologic tumor thickness correlation was calculated. The impact of the imaging-to-surgery time interval and imaging technique on the correlation was explored. Intra-/interrater reliability on radiologic tumor thickness was calculated. The correlation of radiologic-versus-pathologic tumor thickness and its performance as the seventh edition T-category modifier was evaluated. Multivariable analysis assessed the prognostic value of the radiologic tumor thickness for overall survival adjusted for age, seventh edition T-category, and performance status. RESULTS: For 354 consecutive patients, the radiologic-pathologic tumor thickness correlation was similar for the image-to-surgery interval of ≤4.0 weeks (ρ = 0.76) versus 4-8 weeks (ρ = 0.80) but lower in those with more than an 8-week interval (ρ = 0.62). CT and MR imaging had similar correlations (0.76 and 0.80). Intrarater and interrater reliability was excellent (0.88 and 0.84). Excluding 19 cases with an imaging-to-surgery interval of >8 weeks, 335 patients were eligible for further analysis. The radiologic-pathologic tumor thickness correlation was 0.78. The accuracy for upstaging the T-classification based on radiologic tumor thickness was 83% for pathologic T1 and 74% for pathologic T2 tumors. Multivariable analysis confirmed the prognostic value of radiologic tumor thickness (hazard ratio = 1.5, P = .02) for overall survival. CONCLUSIONS: This study demonstrates a good radiologic-pathologic tumor thickness correlation. Intrarater and interrater reliability for radiologic tumor thickness was excellent. Radiologically thicker tumor was predictive of inferior survival.

Adherence to COPD management guidelines in general practice? A review of the literature.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive illness that is mostly managed in the general practice setting. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines are the international gold standard, and it is important to understand how these are being applied in general practice. AIMS: This review aimed to assess the current level of adherence to international best practice guidelines among general practitioners in relation to COPD. METHODS: PubMed and EMBASE searches (from 2012 to 2016) were performed and used the search terms guidelines, COPD, general practitioners, and primary care. Papers were excluded if they were not primary sources, were published before 2012, or did not pertain to a general practice setting. RESULTS: After applying set inclusion and exclusion criteria, 11 studies were retrieved. These papers were grouped under three categories: diagnosis, pharmacological, and non-pharmacological management, based on the GOLD guidelines. CONCLUSIONS: Current studies show significant variability in adherence to the GOLD guidelines. Barriers identified include lack of clarity, unfamiliarity with recommendations, and lack of familiarity with the guidelines. If general practice is expected to manage COPD and other chronic diseases, health service investment is needed to provide appropriate focused guidelines, to support their dissemination and resources to implement them in practice.

Setting the Stage for 2018: How the Changes in the American Joint Committee on Cancer/Union for International Cancer Control Cancer Staging Manual Eighth Edition Impact Radiologists.

The updated eighth edition of the Cancer Staging Manual of the American Joint Committee on Cancer will be implemented in January 2018. There are multiple changes to the head and neck section of the manual, which will be relevant to radiologists participating in multidisciplinary head and neck tumor boards and reading pretreatment head and neck cancer scans. Human papillomavirus-related/p16(+) oropharyngeal squamous cell carcinoma will now be staged separately; this change reflects the markedly better prognosis of these tumors compared with non-human papillomavirus/p16(-) oropharyngeal squamous cell carcinoma. Nodal staging has dramatically changed so that there are different tables for human papillomavirus/p16(+) oropharyngeal squamous cell carcinoma, Epstein-Barr virus-related nasopharyngeal carcinoma, and all other head and neck squamous cell carcinomas. Extranodal extension of tumor is a new clinical feature for this third staging group. In the oral cavity, the pathologically determined depth of tumor invasion is a new staging criterion, while extrinsic tongue muscle invasion is no longer part of staging. This review serves to educate radiologists on the eighth edition changes and their rationale.

Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx.

OBJECTIVE: The rapid worldwide rise in incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies confirming this disease as an entity distinct from traditional OPSCC. Based on pathology, surgical studies have revealed prognosticators specific to HPV-positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)-classification do not differentiate for survival, demonstrating the need for new, HPV-specific OPSCC staging. The objective of this study was to define a pathologic staging system specific to HPV-positive OPSCC. METHODS: Data were assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0) of 704 patients from five cancer centers. Analysis was performed for (a) the AJCC/UICC pathologic staging, (b) newly published clinical staging for non-surgically managed HPV-positive OPSCC, and (c) a novel, pathology-based, "HPVpath" staging system that combines features of the primary tumor and nodal metastases. RESULTS: A combination of AJCC/UICC pT-classification and pathology-confirmed metastatic node count (⩽4 versus ⩾5) yielded three groups: stages I (pT1-T2, ⩽4 nodes), II (pT1-T2, ⩾5 nodes; pT3-T4, ⩽4 nodes), and III (pT3-T4, ⩾5 nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%, 84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked prognostic definition. Newly published HPV-specific clinical stagings from non-surgically managed patients, although prognostic, showed lower precision for this surgically managed cohort. CONCLUSIONS: Three loco-regional "HPVpath" stages are identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary tumor pT-classification and metastatic node count. A workable, pathologic staging system is feasible to establish prognosis and guide adjuvant therapy decisions in surgically-managed HPV-positive OPSCC.

When should we test for voltage-gated potassium channel complex antibodies? A retrospective case control study.

Patients with voltage-gated potassium channel (VGKC)-complex antibodies are increasingly recognized as having central, peripheral or combined phenotypes. With increasing awareness, more patients are tested and the clinical spectrum is expanding. Consequently, clinicians may be uncertain as to which patients should or should not be tested. Previous studies have identified common clinical features, but none has looked at the usefulness of these in predicting seropositive disease. We conducted a case-control study of patients tested for VGKC-complex antibodies over 10years at a regional tertiary neurology centre determining which clinical/biochemical features were associated with antibody-positive disease. We found a marked increase in the numbers tested, although the percentage positive remained low. Antibody titre was highest in central disease (p<0.001). Time from presentation to testing was shorter in those with VGKC-disease (p=0.01). Seizures were present in 11 (69%) of those with VGKC-disease versus three (18%) without (odds ratio [OR] 10.3, 95% confidence interval [CI]: 2.0-52.7, p=0.005). There was an inverse correlation between the antibody titre and serum sodium. A multivariate model selected seizures and hyponatraemia as predictive of VGKC disease (sensitivity 75% and specificity 82%); faciobrachial dystonic movements were specific but insensitive. Interestingly serum alkaline phosphatase was higher in those with VGKC-disease (p=0.016) and highest in those with peripheral disease (p=0.015). An ALP>70u/L was strongly associated with antibody positivity (OR 4.11 95% CI: 1.43-11.8, p=0.007) with a sensitivity of 74.2%. The presence of seizures, faciobrachial movements, and hyponatraemia should raise suspicion of VGKC-disease; alkaline phosphatase may represent a novel biomarker, particularly in those with peripheral disease.

Socioeconomic status, human papillomavirus, and overall survival in head and neck squamous cell carcinomas in Toronto, Canada.

BACKGROUND: Despite universal healthcare in some countries, lower socioeconomic status (SES) has been associated with worse cancer survival. The influence of SES on head and neck cancer (HNC) survival is of immense interest, since SES is associated with the risk and prognostic factors associated with this disease. PATIENTS AND METHODS: Newly diagnosed HNC patients from 2003 to 2010 (n=2124) were identified at Toronto's Princess Margaret Cancer Centre. Principal component analysis was used to calculate a composite score using neighbourhood-level SES variables obtained from the 2006 Canada Census. Associations of SES with overall survival were evaluated in HNC subsets and by p16 status (surrogate for human papillomavirus). RESULTS: SES score was higher for oral cavity (n=423) and p16-positive oropharyngeal cancer (OPC, n=404) patients compared with other disease sites. Lower SES was associated with worse survival [HR 1.14 (1.06-1.22), p=0.0002], larger tumor staging (p<0.001), current smoking (p<0.0001), heavier alcohol consumption (p<0.0001), and greater comorbidity (p<0.0002), but not with treatment regimen (p>0.20). After adjusting for age, sex, and stage, the lowest SES quintile was associated with the worst survival only for OPC patients [HR 1.66 (1.09-2.53), n=832], primarily in the p16-negative subset [HR 1.63 (0.96-2.79)]. The predictive ability of the prognostic models improved when smoking/alcohol was added to the model (c-index 0.71 vs. 0.69), but addition of SES did not (c-index 0.69). CONCLUSION: SES was associated with survival, but this effect was lost after accounting for other factors (age, sex, TNM stage, smoking/alcohol). Lower SES was associated with greater smoking, alcohol consumption, comorbidity, and stage.

General practice career intentions among graduate-entry students: a cross-sectional study at Ireland's newest medical school.

Increased care provision and clinical activity in General Practice in Ireland will have important manpower implications. Recent developments in medical education policy including the introduction of graduate-entry medical degree programmes may help address this issue. The aim of this study was to determine GP career intentions among students on an Irish graduate-entry medical degree programme and to identify factors that influence these. An electronic cross-sectional study of students at University of Limerick Graduate-Entry Medical School (UL-GEMS) was undertaken. We received 139 replies (78% response rate). 41 (29%) reported GP was their current preferred career choice, while 29 (19%) reported it was their preferred career choice on entry to medical school. This first study to present data on GP career intentions among graduate-entry students in Ireland highlights the specialty as a popular preferred career choice among students, both on entry to, and during medical school. The study also identifies factors which are likely to be important in determining career intentions. Further research to examine this issue at other graduate-entry medical schools in Ireland and to determine whether our findings are pursued over time amongst graduates is a priority.

Neuropathological changes in the substantia nigra in schizophrenia but not depression.

Schizophrenia is a chronic, disabling neuropsychiatric disorder characterised by positive, negative and cognitive symptoms. The aetiology is not known, although genetic, imaging and pathological studies have implicated both neurodevelopmental and neurodegenerative processes. The substantia nigra is a basal ganglia nucleus responsible for the production of dopamine and projection of dopaminergic neurons to the striatum. The substantia nigra is implicated in schizophrenia as dopamine has been heavily implicated in the dopamine hypothesis of schizophrenia and the prevalent psychotic symptoms and the monoamine theory of depression, and is a target for the development of new therapies. Studies into the major dopamine delivery pathways in the brain will therefore provide a strong base in improving knowledge of these psychiatric disorders. This post-mortem study examines the cytoarchitecture of dopaminergic neurons of the substantia nigra in schizophrenia (n = 12) and depression (n = 13) compared to matched controls (n = 13). Measures of nucleolar volume, nuclear length and nuclear area were taken in patients with chronic schizophrenia and major depressive disorder against matched controls. Astrocyte density was decreased in schizophrenia compared to controls (p = 0.030), with no change in oligodendrocyte density observed. Significantly increased nuclear cross-sectional area (p = 0.017) and length (p = 0.021), and increased nucleolar volume (p = 0.037) in dopaminergic neurons were observed in schizophrenia patients compared with controls, suggesting nuclear pleomorphic changes. No changes were observed in depression cases compared to control group. These changes may reflect pathological alterations in gene expression, neuronal structure and function in schizophrenia.

Is community treatment best? a randomised trial comparing delivery of cancer treatment in the hospital, home and GP surgery.

BACKGROUND: Care closer to home is being explored as a means of improving patient experience as well as efficiency in terms of cost savings. Evidence that community cancer services improve care quality and/or generate cost savings is currently limited. A randomised study was undertaken to compare delivery of cancer treatment in the hospital with two different community settings. METHODS: Ninety-seven patients being offered outpatient-based cancer treatment were randomised to treatment delivered in a hospital day unit, at the patient's home or in local general practice (GP) surgeries. The primary outcome was patient-perceived benefits, using the emotional function domain of the EORTC quality of life (QOL) QLQC30 questionnaire evaluated after 12 weeks. Secondary outcomes included additional QOL measures, patient satisfaction, safety and health economics. RESULTS: There was no statistically significant QOL difference between treatment in the combined community locations relative to hospital (difference of -7.2, 95% confidence interval: -19·5 to +5·2, P=0.25). There was a significant difference between the two community locations in favour of home (+15·2, 1·3 to 29·1, P=0.033). Hospital anxiety and depression scale scores were consistent with the primary outcome measure. There was no evidence that community treatment compromised patient safety and no significant difference between treatment arms in terms of overall costs or Quality Adjusted Life Year. Seventy-eight percent of patients expressed satisfaction with their treatment whatever their location, whereas 57% of patients preferred future treatment to continue at the hospital, 81% at GP surgeries and 90% at home. Although initial pre-trial interviews revealed concerns among health-care professionals and some patients regarding community treatment, opinions were largely more favourable in post-trial interviews. INTERPRETATION: Patient QOL favours delivering cancer treatment in the home rather than GP surgeries. Nevertheless, both community settings were acceptable to and preferred by patients compared with hospital, were safe, with no detrimental impact on overall health-care costs.

Receptor-specific delivery of protein antigen to dendritic cells by a nanoemulsion formed using top-down non-covalent click self-assembly.

A new class of targeted and immune-evading nanocarrier made using only biological components and facile processes is assembled in a bottom-up fashion. Simple top-down sequential addition of immune-evading or receptor-specific antibody elements conjugated to biosurfactant protein DAMP4 promotes self-assembly at an interface previously formed in the presence of peptide surfactant AM1, leading to a functional display at the interface through non-covalent molecular self-assembly.