Feasibility, Safety, and Efficacy of Aggressive Multimodal Management of Elderly Patients with Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: We aimed to evaluate the safety and efficacy of NAT followed by surgical resection in patients with PDAC aged ≥75 years. SUMMARY BACKGROUND DATA: Whether administration of neoadjuvant therapy (NAT) followed by surgical resection in elderly patients with pancreatic ductal adenocarcinoma (PDAC) is safe and effective is unknown. METHODS: The present study is a three-part comparison of older (≥ 75 years) versus younger (< 75 years) patients in different settings throughout the continuum of PDAC care. The first analysis was a comparison of older versus younger consecutive patients with non-metastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older vs. younger patients who underwent NAT followed by surgical resection, and the third and final analysis was a comparison of older patients who underwent either NAT followed by surgical resection vs. upfront surgical resection. Postoperative complications, overall survival (OS), and time to recurrence (TTR), were compared. Propensity-score matching (PSM) analysis was performed to adjust for potential confounders. RESULTS: In the first analysis, a lower proportion of older patients (n=40) were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared to younger patients (n=214) (65.0% vs. 81.4%, P=0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, P=0.89) as well as surgical resection (57.5% vs 55.6%, P=0.70). In the second analysis, PSM was conducted to compare older (n=54) vs. younger patients (n=54) who underwent NAT followed by surgical resection. There were no significant differences in postoperative complications between the matched groups. While there was a significant difference in overall survival (OS) between older and younger patients (median OS: 16.43 months vs. 30.83 months, P=0.002), importantly, there was no significant difference in time to recurrence (TTR, median: 7.65 months vs. 11.83 months, P=0.215). In the third analysis, older patients who underwent NAT followed by surgical resection (n=48) were compared with similar older patients who underwent upfront surgical resection (n=48). After PSM, there was a significant difference in OS (median OS: 15.78 months vs. 11.51 months, P=0.037) as well as TTR (median TTR: 8.81 months vs. 7.10 months, P=0.046) representing an association with improved outcomes that favored the neoadjuvant approach among older patients alone. CONCLUSIONS: This comprehensive three-part study showed that administration of NAT followed by surgical resection appears to be safe and effective among patients ≥ 75 years of age. An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC.

Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in children aged 6-17 years: a preliminary report of COV006, a phase 2 single-blind, randomised, controlled trial.

BACKGROUND: Vaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than 18 years compared with the same data that are available in adults. METHODS: COV006 is a phase 2, single-blind, randomised, controlled trial of ChAdOx1 nCoV-19 (AZD1222) in children and adolescents at four trial sites in the UK. Healthy participants aged 6-17 years, who did not have a history of chronic respiratory conditions, laboratory-confirmed COVID-19, or previously received capsular group B meningococcal vaccine (the control), were randomly assigned to four groups (4:1:4:1) to receive two intramuscular doses of 5 × 1010 viral particles of ChAdOx1 nCoV-19 or control, 28 days or 84 days apart. Participants, clinical investigators, and the laboratory team were masked to treatment allocation. Study groups were stratified by age, and participants aged 12-17 years were enrolled before those aged 6-11 years. Due to the restrictions in the use of ChAdOx1 nCoV-19 in people younger than 30 years that were introduced during the study, only participants aged 12-17 years who were randomly assigned to the 28-day interval group had received their vaccinations at the intended interval (day 28). The remaining participants received their second dose at day 112. The primary outcome was assessment of safety and tolerability in the safety population, which included all participants who received at least one dose of the study drug. The secondary outcome was immunogenicity, which was assessed in participants who were seronegative to the nucleocapsid protein at baseline and received both prime and boost vaccine. This study is registered with ISRCTN (15638344). FINDINGS: Between Feb 15 and April 2, 2021, 262 participants (150 [57%] participants aged 12-17 years and 112 [43%] aged 6-11 years; due to the change in the UK vaccination policy, the study terminated recruitment of the younger age group before the planned number of participants had been enrolled) were randomly assigned to receive vaccination with two doses of either ChAdOx1 nCoV-19 (n=211 [n=105 at day 28 and n=106 at day 84]) or control (n=51 [n=26 at day 28 and n=25 at day 84]). One participant in the ChAdOx1 nCoV-19 day 28 group in the younger age bracket withdrew their consent before receiving a first dose. Of the participants who received ChAdOx1 nCoV-19, 169 (80%) of 210 participants reported at least one solicited local or systemic adverse event up to 7 days following the first dose, and 146 (76%) of 193 participants following the second dose. No serious adverse events related to ChAdOx1 nCoV-19 administration were recorded by the data cutoff date on Oct 28, 2021. Of the participants who received at least one dose of ChAdOx1 nCoV-19, there were 128 unsolicited adverse events up to 28 days after vaccination reported by 83 (40%) of 210 participants. One participant aged 6-11 years receiving ChAdOx1 nCoV-19 reported a grade 4 fever of 40·2°C on day 1 following first vaccination, which resolved within 24 h. Pain and tenderness were the most common local solicited adverse events for all the ChAdOx1 nCoV-19 and capsular group B meningococcal groups following both doses. Of the 242 participants with available serostatus data, 14 (6%) were seropositive at baseline. Serostatus data were not available for 20 (8%) of 262 participants. Among seronegative participants who received ChAdOx1 nCoV-19, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 after the second dose were higher in participants aged 12-17 years with a longer interval between doses (geometric means of 73 371 arbitrary units [AU]/mL [95% CI 58 685-91 733] and 299 half-maximal inhibitory concentration [IC50; 95% CI 230-390]) compared with those aged 12-17 years who received their vaccines 28 days apart (43 280 AU/mL [95% CI 35 852-52 246] and 150 IC50 [95% CI 116-194]). Humoral responses were higher in those aged 6-11 years than in those aged 12-17 years receiving their second dose at the same 112-day interval (geometric mean ratios 1·48 [95% CI 1·07-2·07] for anti-SARS-CoV-2 IgG and 2·96 [1·89-4·62] for pseudoneutralising antibody titres). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 across all age and interval groups and remained above baseline after a second vaccination. INTERPRETATION: ChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6-17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial. FUNDING: AstraZeneca and the UK Department of Health and Social Care through the UK National Institute for Health and Care Research.

Epinephrine autoinjectors: individualizing device and dosage to optimize anaphylaxis management in the community setting.

Background: Anaphylaxis is the most severe manifestation of a systemic allergic reaction, and, in the community setting, the immediate administration of an epinephrine autoinjector (EAI) can be life-saving. Physicians are tasked with selecting the most appropriate EAI for each individual and counseling patients and/or their caregivers to maximize the likelihood of successful deployment of the EAI. Objective: To offer an evidence-based expert clinical perspective on how physicians might best tailor EAI selection to their patients with anaphylaxis. Methods: A group of eight adult and pediatric allergists with expertise in anaphylaxis management reviewed and assessed the published data and guidelines on anaphylaxis management and EAI device selection. Results: Personalized EAI selection is influenced by intrinsic individual factors, extrinsic factors such as the properties of the individual EAI (e.g., dose, needle length, overall design) as well as cost and coverage. The number and the variety of EAIs available have expanded in most jurisdictions in recent years, which provide a greater diversity of options to meet the characteristics and needs of patients with anaphylaxis. Conclusion: There currently are no EAIs with customizable dose and needle length. Although precise personalization of each patient's EAI remains an optimistic future aspiration, careful consideration of all variables when prescribing EAIs can support optimal management of anaphylaxis.

Stereotactic body radiation therapy for primary liver tumors: An effective liver-directed therapy in the toolbox.

The use of radiation for primary liver cancers has historically been limited because of the risk of radiation-induced liver disease. Treatment fields have become more conformal because of several technical advances, and this has allowed for dose escalation. Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy, is now able to safely treat liver tumors to ablative doses while sparing functional liver parenchyma by using highly conformal therapy. Several retrospective and small prospective studies have examined the use of SBRT for liver cancers; however, there is a lack of well-powered randomized studies to definitively guide management in these settings. Recent advances in systemic therapy for primary liver cancers have improved outcomes; however, the optimal selection criteria for SBRT as a local therapy remain unclear among other liver-directed options such as radiofrequency ablation, transarterial chemoembolization, and radioembolization.

Optimal Neoadjuvant Strategies for Locally Advanced Rectal Cancer by Risk Assessment and Tumor Location.

Neoadjuvant therapy is standard of care for locally advanced rectal cancer (LARC). Advancements in multimodality therapy options and sequencing of radiation therapy (RT), surgery, and chemotherapy make decision-making challenging. Traditional treatment of patients with LARC involves neoadjuvant chemoradiation followed by total mesorectal excision and consideration of adjuvant chemotherapy. Advancement in RT has led to trials offering both short-course and long-course RT with good long-term clinical outcomes. Intensification of therapy in high-risk patients has led to studies of total neoadjuvant therapy with chemotherapy and chemoradiation, now standard management for most LARC. De-escalation of therapy in patients with favorable prognosis has led to several considerations, including non-total mesorectal excision management or neoadjuvant chemotherapy only. Several considerations of patient and disease factors can help inform the optimal chemotherapy regimens in different sequencing of neoadjuvant strategies. Finally, novel biomarkers, such as microsatellite instability, has led to utilization of novel therapies, including neoadjuvant immunotherapy, with substantial response. This review attempts to frame the rapidly growing data in LARC in context of disease and patient risk factors, to inform optimal, personalized treatment of patients with LARC.

Using de novo assembly to identify structural variation of eight complex immune system gene regions.

Driven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity, to which several factors contribute including inheritable structural polymorphism of the underlying genes. Characterizing this variation is challenging due to the complexity of these loci, which contain extensive regions of paralogy, segmental duplication and high copy-number repeats, but recent progress in long-read sequencing and optical mapping techniques suggests this problem may now be tractable. Here we assess this by using long-read sequencing platforms from PacBio and Oxford Nanopore, supplemented with short-read sequencing and Bionano optical mapping, to sequence DNA extracted from CD14+ monocytes and peripheral blood mononuclear cells from a single European individual identified as HV31. We use this data to build a de novo assembly of eight genomic regions encoding four key components of the immune system, namely the human leukocyte antigen, immunoglobulins, T cell receptors, and killer-cell immunoglobulin-like receptors. Validation of our assembly using k-mer based and alignment approaches suggests that it has high accuracy, with estimated base-level error rates below 1 in 10 kb, although we identify a small number of remaining structural errors. We use the assembly to identify heterozygous and homozygous structural variation in comparison to GRCh38. Despite analyzing only a single individual, we find multiple large structural variants affecting core genes at all three immunoglobulin regions and at two of the three T cell receptor regions. Several of these variants are not accurately callable using current algorithms, implying that further methodological improvements are needed. Our results demonstrate that assessing haplotype variation in these regions is possible given sufficiently accurate long-read and associated data. Continued reductions in the cost of these technologies will enable application of these methods to larger samples and provide a broader catalogue of germline structural variation at these loci, an important step toward making these regions accessible to large-scale genetic association studies.

Reducing Readmission of Hospitalized Patients With Depressive Symptoms: A Randomized Trial.

PURPOSE: To determine if hospitalized patients with depressive symptoms will benefit from post-discharge depression treatment with care transition support. METHODS: This is a randomized controlled trial of hospitalized patients with patient health questionnaire-9 score of 10 or more. We delivered the Re-Engineered Discharge (RED) and randomized participants to groups receiving RED-only or RED for Depression (RED-D), a 12-week post-discharge telehealth intervention including cognitive behavioral therapy, self-management support, and patient navigation. Primary outcomes were hospital readmission and reutilization rates at 30 and 90 days post discharge. RESULTS: We randomized 709 participants (353 RED-D, 356 RED-only). At 90 days, 265 (75%) intervention participants had received at least 1 RED-D session (median 4). At 30 days, the intention-to-treat analysis showed no differences between RED-D vs RED-only in hospital readmission (9% vs 10%, incidence rate ratio [IRR] 0.92 [95% CI, 0.56-1.52]) or reutilization (27% vs 24%, IRR 1.14 [95% CI, 0.85-1.54]). The intention-to-treat analysis also showed no differences at 90 days in readmission (28% vs 21%, IRR 1.30 [95% CI, 0.95-1.78]) or reutilization (70% vs 57%, IRR 1.22 [95% CI, 1.01-1.49]). In the as-treated analysis, each additional RED-D session was associated with a decrease in 30- and 90-day readmissions. At 30 days, among 104 participants receiving 3 or more sessions, there were fewer readmissions (3% vs 10%, IRR 0.30 [95% CI, 0.07-0.84]) compared with the control group. At 90 days, among 109 participants receiving 6 or more sessions, there were fewer readmissions (11% vs 21%, IRR 0.52 [95% CI, 0.27-0.92]). Intention-to-treat analysis showed no differences between study groups on secondary outcomes. CONCLUSIONS: Care transition support and post-discharge depression treatment can reduce unplanned hospital use with sufficient uptake of the RED-D intervention.

Leveraging Blood-Based Diagnostics to Predict Tumor Biology and Extend the Application and Personalization of Radiotherapy in Liver Cancers.

While the incidence of primary liver cancers has been increasing worldwide over the last few decades, the mortality has remained consistently high. Most patients present with underlying liver disease and have limited treatment options. In recent years, radiotherapy has emerged as a promising approach for some patients; however, the risk of radiation induced liver disease (RILD) remains a limiting factor for some patients. Thus, the discovery and validation of biomarkers to measure treatment response and toxicity is critical to make progress in personalizing radiotherapy for liver cancers. While tissue biomarkers are optimal, hepatocellular carcinoma (HCC) is typically diagnosed radiographically, making tumor tissue not readily available. Alternatively, blood-based diagnostics may be a more practical option as blood draws are minimally invasive, widely availability and may be performed serially during treatment. Possible blood-based diagnostics include indocyanine green test, plasma or serum levels of HGF or cytokines, circulating blood cells and genomic biomarkers. The albumin-bilirubin (ALBI) score incorporates albumin and bilirubin to subdivide patients with well-compensated underlying liver dysfunction (Child-Pugh score A) into two distinct groups. This review provides an overview of the current knowledge on circulating biomarkers and blood-based scores in patients with malignant liver disease undergoing radiotherapy and outlines potential future directions.

Structural Brain Development and Aggression: A Longitudinal Study in Late Childhood.

This longitudinal study examined the neurodevelopmental correlates of aggression in children, focusing on structural brain properties. A community sample of 110 (60 females) children participated at age 8 years and again at age 10 years. Brain structure was assessed by using magnetic resonance imaging (MRI), and parents reported on child aggression using the Child Behavior Checklist. Analyses examined the relationship between aggression and development of volume of subcortical regions, cortical thickness, and subcortical-cortical structural coupling. Females with relatively high aggression exhibited reduced right hippocampal growth over time. Across males and females, aggression was associated with amygdala- and hippocampal-cortical developmental coupling, with findings for amygdala-cortical coupling potentially indicating reduced top-down prefrontal control of the amygdala in those with increasing aggression over time. Findings suggest that aggressive behaviors may be associated with alterations in normative brain development; however, results were not corrected for multiple comparisons and should be interpreted with caution.

Neural underpinnings of value-guided choice during auction tasks: An eye-fixation related potentials study.

Values are attributed to goods during free viewing of objects which entails multi- and trans-saccadic cognitive processes. Using electroencephalographic eye-fixation related potentials, the present study investigated how neural signals related to value-guided choice evolved over time when viewing household and office products during an auction task. Participants completed a Becker-DeGroot-Marschak auction task whereby half of the stimuli were presented in either a free or forced bid protocol to obtain willingness-to-pay. Stimuli were assigned to three value categories of low, medium and high value based on subjective willingness-to-pay. Eye fixations were organised into five 800 ms time-bins spanning the objects total viewing time. Independent component analysis was applied to eye-fixation related potentials. One independent component (IC) was found to represent fixations for high value products with increased activation over the left parietal region of the scalp. An IC with a spatial maximum over a fronto-central region of the scalp coded the intermediate values. Finally, one IC displaying activity that extends over the right frontal scalp region responded to intermediate- and low-value items. Each of these components responded early on during viewing an object and remained active over the entire viewing period, both during free and forced bid trials. Results suggest that the subjective value of goods are encoded using sets of brain activation patterns which are tuned to respond uniquely to either low, medium, or high values. Data indicates that the right frontal region of the brain responds to low and the left frontal region to high values. Values of goods are determined at an early point in the decision making process and carried for the duration of the decision period via trans-saccadic processes.

Maternal iron homeostasis: effect on placental development and function.

Iron is an essential mineral that participates in oxygen transport, DNA synthesis and repair, and as a cofactor for various cellular processes. Iron deficiency is the most common nutritional deficiency worldwide. Due to blood volume expansion and demands from the fetal-placental unit, pregnant women are one of the populations most at risk of developing iron deficiency. Iron deficiency during pregnancy poses major health concerns for offspring, including intrauterine growth restriction and long-term health complications. Although the underlying mechanisms remain unclear, maternal iron deficiency may indirectly impair fetal growth through changes in the structure and function of the placenta. Since the placenta forms the interface between mother and baby, understanding how the placenta changes in iron deficiency may yield new diagnostic indices of fetal stress in affected pregnancies, thereby leading to earlier interventions and improved fetal outcomes. In this review, we compile current data on the changes in placental development and function that occur under conditions of maternal iron deficiency, and discuss challenges and perspectives on managing the high incidence of iron deficiency in pregnant women.

The cortical oscillatory patterns associated with varying levels of reward during an effortful vigilance task.

We explored how reward and value of effort shapes performance in a sustained vigilance, reaction time (RT) task. It was posited that reward and value would hasten RTs and increase cognitive effort by boosting activation in the sensorimotor cortex and inhibition in the frontal cortex, similar to the horse-race model of motor actions. Participants performed a series of speeded responses while expecting differing monetary rewards (0 pence (p), 1 p, and 10 p) if they responded faster than their median RT. Amplitudes of cortical alpha, beta, and theta oscillations were analysed using the event-related desynchronization method. In experiment 1 (N = 29, with 12 females), reward was consistent within block, while in experiment 2 (N = 17, with 12 females), reward amount was displayed before each trial. Each experiment evaluated the baseline amplitude of cortical oscillations differently. The value of effort was evaluated using a cognitive effort discounting task (COGED). In both experiments, RTs decreased significantly with higher rewards. Reward level sharpened the increased amplitudes of beta oscillations during fast responses in experiment 1. In experiment 2, reward decreased the amplitudes of beta oscillations in the ipsilateral sensorimotor cortex. Individual effort values did not significantly correlate with oscillatory changes in either experiment. Results suggest that reward level and response speed interacted with the task- and baseline-dependent patterns of cortical inhibition in the frontal cortex and with activation in the sensorimotor cortex during the period of motor preparation in a sustained vigilance task. However, neither the shortening of RT with increasing reward nor the value of effort correlated with oscillatory changes. This implies that amplitudes of cortical oscillations may shape upcoming motor responses but do not translate higher-order motivational factors into motor performance.

Transportation noise exposure and anxiety: A systematic review and meta-analysis.

BACKGROUND: Exposure to transportation noise is hypothesized to contribute to anxiety, but consistent associations have not been established. OBJECTIVE: To provide a comprehensive synthesis of the literature by examining associations between traffic-related noise (i.e., road traffic noise, railway noise, aircraft noise and mixed traffic noise) and anxiety. METHODS: We systematically searched Web of Science, Scopus, Embase, PubMed, and PsycINFO for English-language observational studies published up to February 2020 reporting on the traffic noise-anxiety association. We appraised the risk of bias using an assessment tool and the quality of evidence following established guidelines. A random-effects meta-analysis was performed for pooled and separated traffic-related noise sources. RESULTS: Of the 3575 studies identified, 11 fulfilled the inclusion criteria and 9 studies were appropriate for meta-analysis. For the pooled overall effect size between transport noise and anxiety, we found 9% higher odds of anxiety associated with a 10 dB(A) increase in day-evening-night noise level (Lden), with moderate heterogeneity (OR = 1.09, 95% CI: [0.97; 1.23], I2 = 70%). The association was more likely to be significant with more severe anxiety (OR = 1.08, 95% CI: [1.01; 1.15], I2 = 48%). Sub-group analysis revealed that the effects of different noise sources on anxiety were inconsistent and insignificant. The quality of evidence was rated as very low to low. CONCLUSIONS: Our findings support the hypothesis of an association between traffic noise and more severe anxiety. More high-quality studies are needed to confirm associations between different noise types and anxiety, as well as to better understand underlying mechanisms.

Relative importance of perceived physical and social neighborhood characteristics for depression: a machine learning approach.

PURPOSE: The physical and social neighborhood environments are increasingly recognized as determinants for depression. There is little evidence on combined effects of multiple neighborhood characteristics and their importance. Our aim was (1) to examine associations between depression severity and multiple perceived neighborhood environments; and (2) to assess their relative importance. METHODS: Cross-sectional data were drawn from a population-representative sample (N = 9435) from the Netherlands. Depression severity was screened with the Patient Health Questionnaire (PHQ-9) and neighborhood perceptions were surveyed. Supervised machine learning models were employed to assess depression severity-perceived neighborhood environment associations. RESULTS: We found indications that neighborhood social cohesion, pleasantness, and safety inversely correlate with PHQ-9 scores, while increasing perceived distance to green space and traffic were correlated positively. Perceived distance to blue space and urbanicity seemed uncorrelated. Young adults, low-income earners, low-educated, unemployed, and divorced persons were more likely to have higher PHQ-9 scores. Neighborhood characteristics appeared to be less important than personal attributes (e.g., age, marital and employment status). Results were robust across different ML models. CONCLUSIONS: This study suggested that the perceived social environment plays, independent of socio-demographics, a role in depression severity. Contrasted with person-level and social neighborhood characteristics, the prominence of the physical neighborhood environment should not be overstated.

The effect of short-term exposure to the natural environment on depressive mood: A systematic review and meta-analysis.

BACKGROUND: Research suggests that exposure to the natural environment can improve mood, however, current reviews are limited in scope and there is little understanding of moderators. OBJECTIVE: To conduct a comprehensive systematic review and meta-analysis of the evidence for the effect of short-term exposure to the natural environment on depressive mood. METHODS: Five databases were systematically searched for relevant studies published up to March 2018. Risk of bias was evaluated using the Cochrane Risk of Bias (ROB) tool 1.0 and the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool where appropriate. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence overall. A random-effects meta-analysis was performed. 20 potential moderators of the effect size were coded and the machine learning-based MetaForest algorithm was used to identify relevant moderators. These were then entered into a meta-regression. RESULTS: 33 studies met the inclusion criteria. Effect sizes ranged from -2.30 to 0.84, with an unweighted mean effect size of Mg=-0.29,SD=0.60. However, there was significant residual heterogeneity between studies and risk of bias was high. Type of natural environment, type of built environment, gender mix of the sample, and region of study origin, among others, were identified as relevant moderators but were not significant when entered in a meta-regression. The quality of evidence was rated very low to low. An assessment of publication bias was inconclusive. CONCLUSIONS: A small effect was found for reduction in depressive mood following exposure to the natural environment. However, the high risk of bias and low quality of studies limits confidence in the results. The variation in effect size also remains largely unexplained. It is recommended that future studies make use of reporting guidelines and aim to reduce the potential for bias where possible.

Speech and language therapy best practice for patients in prolonged disorders of consciousness: a modified Delphi study.

BACKGROUND: Research regarding speech and language therapy (SLT) for patients in prolonged disorders of consciousness (PDOC) is very limited. The Royal College of Physicians' (RCP) PDOC guideline provides recommendations regarding best practice, but does not give detail about many aspects of assessment and management. As a result, SLTs have little information regarding best practice for this complex patient group. AIMS: To ascertain the degree of consensus amongst expert SLTs regarding SLT best practice for patients in PDOC in order to inform the future development of SLT guidelines. METHODS & PROCEDURES: A two-round modified Delphi technique was used. Participants were recruited from major trauma centres and neurorehabilitation units in England and national SLT clinical excellence networks. To participate, SLTs had to be working on neurosciences, neurosurgery or neurorehabilitation wards that treat adult PDOC patients, or have ≥ 3 years' experience of working with PDOC. The Round 1 questionnaire was developed from the RCP's PDOC guideline and from existing research literature. It included ratings of statements regarding SLT best practice using Likert or temporal scales, with optional written justifications/comments and opportunities for participants to suggest additional statements. The percentage agreement amongst participants was calculated for each Round 1 statement. Written justifications for views were analysed using content analysis. The Round 2 questionnaire contained both quantitative and qualitative feedback from Round 1, allowing participants to reappraise their views. The final degree of consensus was then calculated after completion of both rounds. OUTCOMES & RESULTS: A total of 40 SLTs completed Round 1, with 36 completing Round 2 (90% response rate). Consensus was achieved for 87% (67/77) of statements regarding best practice on a variety of topics including communication, tracheostomy, dysphagia and oral hypersensitivity. The statements represented assessment, management and service delivery components of SLT practice. CONCLUSIONS & IMPLICATIONS: A total of 67 best practice statements were created. The statements provide a useful starting point for the creation of SLT guidelines to support best practice, and also have the potential to be used to advocate for the provision of SLT services for patients in PDOC. Future studies should focus on whether the expert opinion generated here can be borne out in experimental research.

Videoconferencing Psychotherapy and Depression: A Systematic Review.

Introduction:Depression is the leading cause of disability in the world. Despite the prevalence of depression, a small proportion of individuals seek mental health services. A cost-effective method for increasing access to mental health services is the implementation of telemental-health programs. This review aims to summarize the state of the field on the efficacy and effectiveness of videoconferencing psychotherapy (VCP) for the treatment of depression.Materials and Methods:Systematic literature searches were performed using PsychINFO, PubMed, and EMBASE. Specific inclusion criteria were used to identify controlled and uncontrolled studies evaluating VCP for the treatment of depression. Data extraction included study assessment quality, research design, sample size, intervention details, outcome results, intervention effect size, and statistical differences between VCP and in-person (IP) therapy.Results:Of the 1,424 abstracts screened, 92 articles were critically reviewed. Thirty-three articles were included in the review, with 14 randomized controlled studies, 4 controlled nonrandomized studies, and 15 uncontrolled studies. Sample size ranged from 1 to 243 participants. Twenty-one studies reported statistically significant reductions in depressive symptoms following VCP, and the median effect size for studies ranged from medium to the very large range. Most controlled studies reported no statistical differences between VCP and IP groups receiving the same intervention.Conclusions:VCP for the treatment of depression is a promising method for delivering mental health services. More rigorous research is needed to evaluate VCP on depression in various contexts and participants.

More green space is related to less antidepressant prescription rates in the Netherlands: A Bayesian geoadditive quantile regression approach.

BACKGROUND: Exposure to green space seems to be beneficial for self-reported mental health. In this study we used an objective health indicator, namely antidepressant prescription rates. Current studies rely exclusively upon mean regression models assuming linear associations. It is, however, plausible that the presence of green space is non-linearly related with different quantiles of the outcome antidepressant prescription rates. These restrictions may contribute to inconsistent findings. OBJECTIVE: Our aim was: a) to assess antidepressant prescription rates in relation to green space, and b) to analyze how the relationship varies non-linearly across different quantiles of antidepressant prescription rates. METHODS: We used cross-sectional data for the year 2014 at a municipality level in the Netherlands. Ecological Bayesian geoadditive quantile regressions were fitted for the 15%, 50%, and 85% quantiles to estimate green space-prescription rate correlations, controlling for physical activity levels, socio-demographics, urbanicity, etc. RESULTS: The results suggested that green space was overall inversely and non-linearly associated with antidepressant prescription rates. More important, the associations differed across the quantiles, although the variation was modest. Significant non-linearities were apparent: The associations were slightly positive in the lower quantile and strongly negative in the upper one. CONCLUSION: Our findings imply that an increased availability of green space within a municipality may contribute to a reduction in the number of antidepressant prescriptions dispensed. Green space is thus a central health and community asset, whilst a minimum level of 28% needs to be established for health gains. The highest effectiveness occurred at a municipality surface percentage higher than 79%. This inverse dose-dependent relation has important implications for setting future community-level health and planning policies.

C5orf30 is a negative regulator of tissue damage in rheumatoid arthritis.

The variant rs26232, in the first intron of the chromosome 5 open reading frame 30 (C5orf30) locus, has recently been associated with both risk of developing rheumatoid arthritis (RA) and severity of tissue damage. The biological activities of human C5orf30 are unknown, and neither the gene nor protein show significant homology to any other characterized human sequences. The C5orf30 gene is present only in vertebrate genomes with a high degree of conservation, implying a central function in these organisms. Here, we report that C5orf30 is highly expressed in the synovium of RA patients compared with control synovial tissue, and that it is predominately expressed by synovial fibroblast (RASF) and macrophages in the lining and sublining layer of the tissue. These cells play a central role in the initiation and perpetuation of RA and are implicated in cartilage destruction. RASFs lacking C5orf30 exhibit increased cell migration and invasion in vitro, and gene profiling following C5orf30 inhibition confirmed up-regulation of genes involved in cell migration, adhesion, angiogenesis, and immune and inflammatory pathways. Importantly, loss of C5orf30 contributes to the pathology of inflammatory arthritis in vivo, because inhibition of C5orf30 in the collagen-induced arthritis model markedly accentuated joint inflammation and tissue damage. Our study reveal C5orf30 to be a previously unidentified negative regulator of tissue damage in RA, and this protein may act by modulating the autoaggressive phenotype that is characteristic of RASFs.