Long-Term Echocardiographic and Clinical Outcomes After Invasive and Non-Invasive Therapies for Sub-Massive and Massive Acute Pulmonary Embolism.

AIM: Acute pulmonary embolism (PE) is a significant cause of mortality in the hospital setting. The objective of this study was to outline the long-term outcomes after surgical and non-surgical management for patients with massive and submassive PE. METHODS: Population cohort observational study evaluating all patients who presented to three tertiary hospitals in the state of Western Australia with access to cardiothoracic services over 5 years (2013-2018). Reviewed notes of all patients as well as radiology, linked mortality data and all available echocardiography studies at the primary hospital. RESULTS: In total, 245 patients were identified, of which 41 received surgical management and 204 non-surgical management; demographic data was similar. Clinically, the surgical group had higher rates of shock requiring vasopressors, severe bradycardia, or cardiopulmonary resuscitation prior to intervention. The 28-day mortality was not statistically significantly different between the surgical embolectomy group (2/41 [4.2%]) and the non-surgical group (17/201 [8.3%]) (p=0.382). There was no difference in 12-month mortality, including when this was adjusted for vasopressors, right ventricular (RV) strain, troponin, and brain natriuretic peptide. In the massive PE sub-group, 28-day mortality was not significantly different: 2/29 (6.9%) surgical group vs 7/34 (20.2%) non-surgical group (p=0.064). Higher rates of severe RV impairment and dilatation were present in the surgical group. All patients with available echocardiography studies at outpatient follow-up returned to normal or mild RV impairment. CONCLUSION: Patients who presented with massive or submassive PE had similar outcomes whether treated with surgical or non-surgical management. Surgical embolectomy is a safe option in a cardiothoracic centre setting.

Clinically Integrated Molecular Diagnostics in Adenoid Cystic Carcinoma.

BACKGROUND: Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy without effective systemic therapies. Delineation of molecular profiles in ACC has led to an increased number of biomarker-stratified clinical trials; however, the clinical utility and U.S.-centric financial sustainability of integrated next-generation sequencing (NGS) in routine practice has, to our knowledge, not been assessed. MATERIALS AND METHODS: In our practice, NGS genotyping was implemented at the discretion of the primary clinician. We combined NGS-based mutation and fusion detection, with MYB break-apart fluorescent in situ hybridization (FISH) and MYB immunohistochemistry. Utility was defined as the fraction of patients with tumors harboring alterations that are potentially amenable to targeted therapies. Financial sustainability was assessed using the fraction of global reimbursement. RESULTS: Among 181 consecutive ACC cases (2011-2018), prospective genotyping was performed in 11% (n = 20/181; n = 8 nonresectable). Testing identified 5/20 (25%) NOTCH1 aberrations, 6/20 (30%) MYB-NFIB fusions (all confirmed by FISH), and 2/20 (10%) MYBL1-NFIB fusions. Overall, these three alterations (MYB/MYBL1/NOTCH1) made up 65% of patients, and this subset had a more aggressive course with significantly shorter progression-free survival. In 75% (n = 6/8) of nonresectable patients, we detected potentially actionable alterations. Financial analysis of the global charges, including NGS codes, indicated 63% reimbursement, which is in line with national (U.S.-based) and international levels of reimbursement. CONCLUSION: Prospective routine clinical genotyping in ACC can identify clinically relevant subsets of patients and is approaching financial sustainability. Demonstrating clinical utility and financial sustainability in an orphan disease (ACC) requires a multiyear and multidimensional program. IMPLICATIONS FOR PRACTICE: Delineation of molecular profiles in adenoid cystic carcinoma (ACC) has been accomplished in the research setting; however, the ability to identify relevant patient subsets in clinical practice has not been assessed. This work presents an approach to perform integrated molecular genotyping of patients with ACC with nonresectable, recurrent, or systemic disease. It was determined that 75% of nonresectable patients harbor potentially actionable alterations and that 63% of charges are reimbursed. This report outlines that orphan diseases such as ACC require a multiyear, multidimensional program to demonstrate utility in clinical practice.

An examination of user costs in relation to smokers using a cessation service based in the UK.

BACKGROUND: Smoking cessation services provide support to smokers who desire to quit. Published studies to date have looked at the cost and benefit of service provision but typically focus on clinical trial data. Using routinely collected observational data, this study examined the costs involved in providing a service in terms of average health care expenditure per successful quit attempt in addition to population - level cost-effectiveness measures. METHODS: Data were analysed from Quit-51 smoking cessation service across five English regions between March 2013 and March 2016 (n = 9116). For each user, costs were estimated in relation to: (i) time spent with advisers; (ii) prescription of pharmacotherapy. The total costs compared against self-reported quit at 12 weeks, which represents the time period for which the service is offered. Cost per quit (CPQ), with 95% confidence interval (CI), was calculated by relating total expenditure to the number of quitters, firstly for the whole dataset and then by subgroups of key categorical variables, namely; gender, age group, the Fagerstrom test for nicotine dependence (FTND) and Index of Multiple Deprivation (IMD). Confidence intervals (CIs) for the mean estimates were derived using a non-parametric bootstrap procedure. Parameters derived from the calculation in relation to treatment were used to estimate potential long-term population outcomes under a scenario where the Quit 51 prescription was rolled out nationally. RESULTS: The overall mean CPQ for this sample as estimated at 12 weeks was £403.51 (95% CI = £393.36 to £413.76). The estimated CPQs at this time point were comparable for those aged 12-19 (£423.56, 95% CI = £369.45 to £492.60) and those aged 20-29 (£430.76, 95% CI = £395.95 to £470.56). Differences were also seen in relation to other subgroups considered. The treatment parameters translated to a projected increase of 1.5 quality-adjusted life years (QALYs) per 1000 smokers in the short-term and 23.4 QALYS per 1000 smokers based on a lifetime horizon. CONCLUSIONS: These figures throw light on service expenditure for each successful quit over the timeframe for which the service is offered in addition to highlighting variability in these costs across different subgroups of the user population.

Using Robots at Home to Support Patients With Chronic Obstructive Pulmonary Disease: Pilot Randomized Controlled Trial.

BACKGROUND: Socially assistive robots are being developed for patients to help manage chronic health conditions such as chronic obstructive pulmonary disease (COPD). Adherence to medication and availability of rehabilitation are suboptimal in this patient group, which increases the risk of hospitalization. OBJECTIVE: This pilot study aimed to investigate the effectiveness of a robot delivering telehealth care to increase adherence to medication and home rehabilitation, improve quality of life, and reduce hospital readmission compared with a standard care control group. METHODS: At discharge from hospital for a COPD admission, 60 patients were randomized to receive a robot at home for 4 months or to a control group. Number of hospitalization days for respiratory admissions over the 4-month study period was the primary outcome. Medication adherence, frequency of rehabilitation exercise, and quality of life were also assessed. Implementation interviews as well as benefit-cost analysis were conducted. RESULTS: Intention-to-treat and per protocol analyses showed no significant differences in the number of respiratory-related hospitalizations between groups. The intervention group was more adherent to their long-acting inhalers (mean number of prescribed puffs taken per day=48.5%) than the control group (mean 29.5%, P=.03, d=0.68) assessed via electronic recording. Self-reported adherence was also higher in the intervention group after controlling for covariates (P=.04). The intervention group increased their rehabilitation exercise frequency compared with the control group (mean difference -4.53, 95% CI -7.16 to -1.92). There were no significant differences in quality of life. Of the 25 patients who had the robot, 19 had favorable attitudes. CONCLUSIONS: This pilot study suggests that a homecare robot can improve adherence to medication and increase exercise. Further research is needed with a larger sample size to further investigate effects on hospitalizations after improvements are made to the robots. The robots could be especially useful for patients struggling with adherence. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000259549; http://www.anzctr.org.au (Archived by WebCite at  http://www.webcitation.org/6whIjptLS).

The effects of expressive writing before or after punch biopsy on wound healing.

OBJECTIVE: Recent studies have shown that written emotional disclosure (expressive writing) performed in the two weeks prior to wounding improves healing of punch biopsy wounds. In many clinical settings, it would be more practical for patients to perform this intervention after wounding. The aim of this study was to investigate whether expressive writing could speed the healing of punch biopsy wounds if writing was performed after wounds were made. METHODS: One hundred and twenty-two healthy participants aged between 18 and 55years were randomly allocated to one of four groups in a 2 (intervention) by 2 (timing) design. Participants performed either expressive writing or neutral writing, either before or after receiving a 4mm punch biopsy wound. Wounds were photographed on day 10 (primary endpoint) and day 14 after the biopsy to measure epithelisation. Participants also completed questionnaires on stress and affect two weeks prior to the biopsy, on the day of biopsy and two weeks after biopsy. RESULTS: There was a significant difference in healing at day 10 between groups, χ2(3, N=97)=8.84, p=0.032. A significantly greater proportion of participants who performed expressive writing before the biopsy had fully reepithelialised wounds on day 10 compared to participants who performed neutral writing either before or after wounding, with no other significant differences between groups. Amongst people who wrote expressively after wounding, those who finished writing over the first 6days were significantly more likely to be healed at 14days than those who finished writing later. There were significant differences in positive and negative affect over the healing period between the pre and post expressive writing groups. CONCLUSIONS: Expressive writing can improve healing if it is performed prior to wounding. Performing expressive writing after wounding may be able to improve healing depending on the timing of writing and wound assessment. Expressive writing causes affect to worsen followed by subsequent improvement and it is important to consider this in the timing of intervention delivery. Further research with patient groups is required to determine the clinical relevance of these findings.

The impact of illness perceptions and disease severity on quality of life in congenital heart disease.

BACKGROUND: Despite an increasing prevalence of adults living with a CHD, little is known about the psychosocial impact of CHD. We sought to investigate the relative impact of disease severity and patients' perceptions about their condition on depression, anxiety, and quality of life over a period of a year. METHODS: A total of 110 patients aged over 16 years completed an initial questionnaire containing measures for anxiety, depression, quality of life, and illness perceptions when they attended the Adult Congenital Heart Disease Clinic. Cardiologists rated the patients' disease severity and illness course. A year later, patients were invited to complete the same measures. Regression analyses were performed to determine the relative impact of illness perceptions and disease severity on psychological outcomes a year later. RESULTS: At baseline, 23% of the study population had depressive symptoms and 30% had elevated trait anxiety. After controlling for associations with disease-related variables, illness perceptions explained 28% of the variance in depression, 40% anxiety, and 27% overall quality of life at baseline. Baseline illness perceptions bivariately predicted quality of life, cardiac anxiety, and depression 1 year later, and regression analyses controlling for other factors showed that they were significant predictors of outcomes 1 year later. CONCLUSION: Symptoms of depression and anxiety are common among adults with CHD. Patients' illness perceptions are related to psychological outcomes, especially cross-sectionally. Future research could investigate whether an intervention to discuss patients' perceptions about their CHD can improve mental health and quality of life.

The Effects of Relaxation Before or After Skin Damage on Skin Barrier Recovery: A Preliminary Study.

OBJECTIVES: Psychological interventions administered before wounding can reduce stress and improve healing. However, in many cases, it would be more practical for interventions to be delivered after wounding. This preliminary study investigated whether a brief relaxation intervention could improve healing when administered either before or after skin damage produced by tape stripping in comparison to a control group. METHODS: One hundred twenty-one healthy adults were randomized into one of three groups: (a) relaxation prestripping group, (b) relaxation poststripping group, or (c) no relaxation. Participants completed measures of stress, fatigue, relaxation, and pain. Relaxation consisted of listening to 20 minutes of guided relaxation, whereas the control condition was quiet reading for 20 minutes. Skin barrier function was measured using transepidermal water loss at baseline, immediately after tape stripping and 25 minutes later. RESULTS: Relaxation either before or after tape stripping improved skin barrier recovery compared with the control group (F(2,92) = 3.58, p = .032, partial η = 0.074). Participants who took part in the relaxation intervention were significantly more relaxed and reported greater reductions in pain than the control group did 25 minutes after tape stripping. Perceived stress over the last month was not significantly related to healing. CONCLUSIONS: This study showed that a relaxation intervention had a beneficial effect on skin barrier recovery regardless of whether the intervention was administered before or after wounding. Future research needs to replicate these findings in other wound types and in clinical settings, and investigate the biological mechanisms involved.

What do we know about what happens to myometrial function as women age?

Much has been written about the effects of aging on reproductive function, especially female fertility. Much less is known about how aging may affect the contractility of the smooth muscle within the uterus, the myometrium. The myometrium is active through a woman's entire life, not just during pregnancy. Here we will discuss briefly the contractile functions of the uterus and the changes it undergoes throughout the stages of a woman's life from menstruation and the menopause, before evaluating the evidence for any changes in myometrial contractility and responses as women age, with a particular focus on women of advanced maternal age. We present original contractility analysis for the widest data set for human myometrium so far examined, and determine inherent spontaneous activity as well as responses to depolarisation and stimulation with oxytocin. Our data show that in the non-pregnant state there is a significant decrease in contractility for both spontaneous and depolarised-induced contractions, with age. We suggest that muscle atrophy and down regulation of Ca channels may account for this. Interestingly in pregnant myometrium we found a wide range of contractile ability between women and little evidence for decreased spontaneous activity between the ages of 25-40. Oxytocin responses appear to be more affected by aging, a finding that is consistent with previously reported clinical findings, and may partly be the result of membrane lipids such as cholesterol, increasing as women age. The marked differences between the age-related decline of force beyond age 30 in non-pregnant uterus, and the lack of difference in the pregnant state over this period, shows that the uterus retains its ability to respond to gestational hormones. The growth of the pregnant uterus and increase in content of myofibrillar proteins, may abolish any previous age-related force deficit. This finding is consistent with what is apparent for postmenopausal women in their 50s and 60s; that with the appropriate hormonal stimulation the uterus can allow an embryo to implant, and then without further intervention, carry the foetus to term. It is tempting therefore to speculate that unlike other well documented declines in female reproductive functions with age, the myometrium remains able to function into a woman's 7th decade.

The effect of expressive writing on wound healing: Immunohistochemistry analysis of skin tissue two weeks after punch biopsy wounding.

OBJECTIVE: To investigate the effects of expressive writing and its timing (pre or post wounding) on re-epithelialisation and leucocyte subsets within healing tissue. We previously showed expressive writing pre-wounding improved re-epithelialisation. Here we investigate cellular processes in the wound. METHODS: In a 2(writing content) x 2(writing timing) randomized trial, 122 participants were randomized to perform either expressive or control writing, before or after a 4 mm punch biopsy wound. On day 14 post-wounding, participants had a 5 mm punch biopsy of the initial wound. Seven of 16 primary registered outcomes were analysed, including re-epithelialisation from two photographs of the 4 mm biopsy (previously reported). This paper reports immunohistochemistry analysis of five primary outcomes - Langerhans cells, immune cell activation (HLA and CD3+), and macrophages (CD68 and MPO) - in the 5 mm biopsies in a random sample of 96 participants. RESULTS: Participants who performed either writing task pre-wounding had greater Langerhans cell infiltration, than those who wrote post-wounding (F(1,85) = 7.86, p = .006, ηp2 = 0.08). Those who performed expressive writing also had greater Langerhans cell infiltration than those who performed control writing (F(1,85) = 4.00, p = .049, ηp2 = 0.04). There were no significant group or interaction effects on immune cell activation or macrophages. Healed wounds on day 10 had lower levels of macrophages (z = -1.96, p = .050), and CD3+ cells (z = -1.99, p = .046) than non-healed wounds. CONCLUSION: Langerhans cells in the healing skin are affected by the timing and topic of writing. More research is needed to further explore timing and corroborate these results. CLINICAL TRIALS REGISTRATION: Registered at https://www.anzctr.org.au/ (Trial ID: ACTRN12614000971639).

Telomere Attrition in Induced Pluripotent Stem Cell-Derived Neurons From ALS/FTD-Related C9ORF72 Repeat Expansion Carriers.

The GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dysregulated DNA damage response and the generation of reactive oxygen species (ROS) have been postulated as major drivers of toxicity in C9ORF72 pathogenesis. Telomeres are tandem-repeated nucleotide sequences that are located at the end of chromosomes and protect them from degradation. Interestingly, it has been established that telomeres are sensitive to ROS. Here, we analyzed telomere length in neurons and neural progenitor cells from several induced pluripotent stem cell (iPSC) lines from control subjects and C9ORF72 repeat expansion carriers. We found an age-dependent decrease in telomere length in two-month-old iPSC-derived motor neurons from C9ORF72 carriers as compared to control subjects and a dysregulation in the protein levels of shelterin complex members TRF2 and POT1.

Coldzyme® Mouth Spray reduces duration of upper respiratory tract infection symptoms in endurance athletes under free living conditions.

Upper respiratory tract infection (URTI) can compromise athlete preparation and performance, so countermeasures are desirable. The aim of this study was to assess the effects of ColdZyme® Mouth Spray (ColdZyme) on self-reported upper respiratory tract infection in competitive endurance athletes under free-living conditions. One hundred and twenty-three endurance-trained, competitive athletes (recruited across 4 sites in England, UK) were randomised to control (no treatment, n = 61) or ColdZyme (n = 62) for a 3-month study period (between December 2017 and March 2018; or December 2018 and April 2019). They recorded daily training and illness symptoms (Jackson common cold questionnaire) during the study period. A total of 130 illness episodes were reported during the study with no difference in incidence between groups (episodes per person: 1.1 ± 0.9 Control, 1.0 ± 0.8 ColdZyme, P = 0.290). Episode duration was significantly shorter in ColdZyme compared to Control: Control 10.4 ± 8.5 days vs. ColdZyme 7.7 ± 4.0 days, P = 0.016). Further analysis to compare episodes with poor vs. good compliance with ColdZyme instructions for use (IFU) within the ColdZyme group showed a greater reduction in duration of URTI when compliance was good (9.3 ± 4.5 days in ColdZyme poor IFU compliance vs. 6.9 ± 3.5 days in ColdZyme good IFU compliance, P = 0.040). ColdZyme may be an effective countermeasure to reduce URTI duration, which was significantly lower (by 26-34%) in the ColdZyme treatment group (with no influence on incidence). This may have implications for athlete performance.

A Nanopore Sequencing-Based Assay for Rapid Detection of Gene Fusions.

Structural chromosomal rearrangements leading to gene fusions are strong driver mutations in a variety of tumors. Identification of specific gene fusions can be essential for distinguishing benign from malignant conditions and for recognizing specific subtypes of neoplasms that can have different management and prognosis. Rapid identification of gene fusions is particularly critical for patients with acute leukemia who cannot wait more than a few days before initiating treatment and for whom treatment can be dramatically different depending on the leukemia subtype. We have developed an assay for rapid detection of oncogenic gene fusions (within 24 hours) that takes advantage of the long reads and real-time data generation of the Oxford Nanopore MinION sequencing system. By using a modification of the anchored multiplex PCR method for library construction, we confidently identified BCR-ABL1 fusion transcripts, with >100 reads within 15 minutes of sequencing. By using formalin-fixed, paraffin-embedded specimens routinely tested in our clinical molecular laboratory, fusions were successfully identified within 5 hours from acquisition of Illumina-ready libraries and 30 minutes of sequencing initiation, including cases diluted to a tumor fraction of 5%. In conclusion, we have developed a nanopore-based sequencing assay that can decrease turnaround time for detection of fusion oncogenes and may be a valid approach for laboratories with low specimen volume and for cases in need of rapid results.

Expediting Comprehensive Molecular Analysis to Optimize Initial Treatment of Lung Cancer Patients With Minimal Smoking History.

INTRODUCTION: Lung cancer patients with tumors harboring actionable alterations can achieve very durable responses to first-line targeted therapy. However, identifying targetable alterations using next-generation sequencing (NGS) is a complex and time-intensive process. As actionable genetic alterations are enriched in lung cancers arising in patients with limited smoking history, we designed a workflow to expedite NGS testing for this group. METHODS: We developed a protocol to allow for next-day extraction of nucleic acids from frozen tissue. Specimens were designated as high priority during sequencing. We determined the interval between biopsy and NGS results to evaluate whether the workflow reduced the pre-analytical period and in-laboratory turnaround time and allowed for rapid initiation of genotype-matched therapy. RESULTS: Between January 2017 and May 2018, 21 patients participated in the expedited sequencing program. The median interval between biopsy and NGS results was 10.7 days. Six patients received results within 1 week of biopsy. Performing molecular analysis on frozen tissue and prioritizing sequencing and analysis of these specimens reduced the pre-analytical period from 3.5 to 1.3 days (p < 0.0001) and shortened in-laboratory turnaround time by 3 days (11.8 versus 8.4 business days, p < 0.0001). Ninety-three percent of patients with an actionable molecular alteration received first-line targeted therapy. The median time-to-initiation of treatment was 19.7 days from biopsy. CONCLUSIONS: Sequencing and analyzing nucleic acids from frozen tissue is a practical strategy for shortening the time to matched therapy. The significant advantage of upfront treatment with targeted therapies in subsets of lung cancer patients provides rationale for developing workflows that accelerate comprehensive molecular analysis.

Clinical Validation of a Cell-Free DNA Gene Panel.

The use of liquid biopsies to identify driver mutations in patients with solid tumors holds great promise for performing targeted therapy selection, monitoring disease progression, and detecting treatment resistance mechanisms. We describe herein the development and clinical validation of a 28-gene cell-free DNA panel that targets the most common genetic alterations in solid tumors. Bioinformatic and variant filtering solutions were developed to improve test sensitivity and specificity. The panel and these tools were used to analyze commercially available controls, allowing establishment of a limit of detection allele fraction cutoff of 0.25%, with 100% (95% CI, 81.5%-100%) specificity and 89.8% (95% CI, 81.0%-94.9%) sensitivity. In addition, we analyzed a total of 163 blood samples from patients with metastatic cancer (n = 123) and demonstrated a >90% sensitivity for detecting previously identified expected mutations. Longitudinal monitoring of patients revealed a strong correlation of variant allele frequency changes and clinical outcome. Additional clinically relevant information included identification of resistance mutations in patients receiving targeted treatment and detection of complex patterns of mutational heterogeneity. Achieving lower limits of detection will require additional improvements to molecular barcoding; however, these data strongly support clinical implementation of cell-free DNA panels in advanced cancer patients.

Factors moderating the relative effectiveness of varenicline and nicotine replacement therapy in clients using smoking cessation services.

AIMS: To assess how far the greater effectiveness of varenicline over nicotine replacement therapy (NRT) is moderated by characteristics of the smokers or setting in clinical practice. DESIGN: We used observational data from 22 472 treatment episodes between 2013 and 2016 from smoking cessation services in England to assess whether differences between varenicline and NRT were moderated by a set of smoker and setting characteristics: these included level of social deprivation, age, gender, ethnic group, nicotine dependence and treatment context. From the above, 15 640 episodes were analysed in relation to 4-week quit and 14 273 episodes at 12 weeks. All two-way interactions involving pharmacotherapy were fitted in addition to the main effects and a parsimonious model identified using a backwards stepwise selection procedure. SETTING: England PARTICIPANTS: Clients of smoking cessation service (number of individuals in 4-week quit analysis = 15 640). MEASUREMENTS: Four-week carbon monoxide-validated (primary outcome) and 12-week self-reported (secondary outcome) quit success/failure. FINDINGS: At both follow-up points, varenicline was associated with higher success rates overall [P < 0.001 at both 4 and 12 weeks; adjusted odds ratio (OR) varenicline versus NRT = 1.82 (95% confidence interval (CI) = 1.61, 2.06) and 2.58 (95% CI = 2.26, 2.94) at 4 and 12 weeks, respectively]. At 12 weeks, the relative benefits of varenicline were found to be influenced by the setting in which advice was provided [P < 0.001 for interaction pharmacotherapy × setting; adjusted odds ratio for varenicline × pharmacy setting = 0.53 (95% CI = 0.42, 0.69) and for varenicline × general practice (GP) setting = 0.79 (95% CI = 0.64, 0.98) against a baseline of 1 for varenicline × community setting]. The same trends were evident at 4 weeks, but this did not translate to statistical significance. There was inconclusive evidence for moderating effects of other variables. CONCLUSIONS: Varenicline use was associated with higher smoking cessation rates than nicotine replacement therapy in routine clinical practice, irrespective of a wide range of smoker characteristics, but the difference was less in certain intervention settings, most notably pharmacy but also GP practice, compared with community setting.

Facilitators and barriers to physical activity following pulmonary rehabilitation in COPD: a systematic review of qualitative studies.

Pulmonary rehabilitation has short-term benefits on dyspnea, exercise capacity and quality of life in COPD, but evidence suggests these do not always translate to increased daily physical activity on a patient level. This is attributed to a limited understanding of the determinants of physical activity maintenance following pulmonary rehabilitation. This systematic review of qualitative research was conducted to understand COPD patients' perceived facilitators and barriers to physical activity following pulmonary rehabilitation. Electronic databases of published data, non-published data, and trial registers were searched to identify qualitative studies (interviews, focus groups) reporting the facilitators and barriers to physical activity following pulmonary rehabilitation for people with COPD. Thematic synthesis of qualitative data was adopted involving line-by-line coding of the findings of the included studies, development of descriptive themes, and generation of analytical themes. Fourteen studies including 167 COPD patients met the inclusion criteria. Seven sub-themes were identified as influential to physical activity following pulmonary rehabilitation. These included: intentions, self-efficacy, feedback of capabilities and improvements, relationship with health care professionals, peer interaction, opportunities following pulmonary rehabilitation and routine. These encapsulated the facilitators and barriers to physical activity following pulmonary rehabilitation and were identified as sub-themes within the three analytical themes, which were beliefs, social support, and the environment. The findings highlight the challenge of promoting physical activity following pulmonary rehabilitation in COPD and provide complementary evidence to aid evaluations of interventions already attempted in this area, but also adds insight into future development of interventions targeting physical activity maintenance in COPD.

Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer.

PURPOSE: Targeted therapy is the cornerstone of treatment of advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Next-generation sequencing (NGS), the preferred method for genotyping, typically requires several weeks. Here, we assessed workflows designed to rapidly identify patients with actionable EGFR mutations and reduce time to initiation (TTI) of epidermal growth factor receptor (EGFR)-directed therapy. PATIENTS AND METHODS: We performed rapid testing for EGFR L858R mutations and exon 19 deletions on paraffin-embedded or frozen section biopsy specimens from newly diagnosed patients with metastatic NSCLC by using an EGFR-specific assay (rapid test). To determine clinical utility, we assessed concordance with NGS results, turnaround time, and TTI of EGFR therapy, and we evaluated reimbursement data. RESULTS: Between January 2015 and September 2017, we performed 243 rapid EGFR tests and identified EGFR mutations in 43 patients (18%). With NGS results as a reference, sensitivity and specificity of the rapid EGFR polymerase chain reaction assay were 98% and 100%, respectively. The median turnaround time for NGS was 14 days, compared with 7 days for rapid testing (P < .001). In the rapid group, 95% of patients received an EGFR inhibitor in the first-line setting. The median TTI of EGFR therapy was significantly shorter in the rapid cohort when compared with 121 historical cases (22 v 37 days; P = .01). Escalation of the initiative into an interdisciplinary ultra-rapid next-day frozen-section workflow for highly symptomatic patients (n = 8) resulted in a reduction in the median (± standard deviation) turnaround time to 1 ± 0.4 days and allowed several patients to initiate therapy within 1 week of biopsy. An extended 9-month clinical evaluation phase confirmed operational sustainability (turnaround times: ultra-rapid, 0.81 ± 0.4 days; rapid, 3 ± 1.5 days), and a 63% reimbursement rate indicated financial sustainability. CONCLUSION: Rapid genotyping facilitates earlier initiation of EGFR-directed therapies without compromising NGS workflows.

The effects of psychological interventions on wound healing: A systematic review of randomized trials.

PURPOSE: Psychological stress has been shown to delay wound healing. Several trials have investigated whether psychological interventions can improve wound healing, but to date, this evidence base has not been systematically synthesized. The objective was to conduct a systematic review of randomized controlled trials in humans investigating whether psychological interventions can enhance wound healing. METHODS: A systematic review was performed using PsychINFO, CINAHL, Web of Science, and MEDLINE. The searches included all papers published in English up until September 2016. The reference lists of relevant papers were screened manually to identify further review articles or relevant studies. Nineteen studies met inclusion criteria and were included in the review. RESULTS: Fifteen of nineteen studies were of high methodological quality. Six studies were conducted with acute experimentally created wounds, five studies with surgical patients, two studies with burn wounds, two studies with fracture wounds, and four studies were conducted with ulcer wounds. Post-intervention standardized mean differences (SMD) between groups across all intervention types ranged from 0.13 to 3.21, favouring improved healing, particularly for surgical patients and for relaxation interventions. However, there was some evidence for publication bias suggesting negative studies may not have been reported. Due to the heterogeneity of wound types, population types, and intervention types, it is difficult to pool effect sizes across studies. CONCLUSIONS: Current evidence suggests that psychological interventions may aid wound healing. Although promising, more research is needed to assess the efficacy of each intervention on different wound types. Statement of contribution What is already known on this subject? Psychological stress negatively affects wound healing. A number of studies have investigated whether psychological interventions can improve healing. However, no systematic reviews have been conducted. What does this study add? Synthesis and review of 19 trials conducted on psychological interventions and wound healing. Most evidence supports improved healing, particularly for surgical wounds and relaxation interventions. More research is needed on different intervention types with clinical wounds and into mechanisms of action.

A Pilot Randomized Trial of a Companion Robot for People With Dementia Living in the Community.

OBJECTIVES: To investigate the affective, social, behavioral, and physiological effects of the companion robot Paro for people with dementia in both a day care center and a home setting. DESIGN: A pilot block randomized controlled trial over 12 weeks. Participants were randomized to the intervention (Paro) or control condition (standard care). SETTING: Two dementia day care centers and participants' homes in Auckland, New Zealand. PARTICIPANTS: Thirty dyads (consisting of a care recipient with dementia and their caregiver) took part in this study. All care recipients attended dementia day care centers at Selwyn Foundation and had a formal diagnosis of dementia. INTERVENTION: Thirty-minute unstructured group sessions with Paro at the day care center were run 2 to 3 times a week for 6 weeks. Participants also had Paro at home for 6 weeks. MEASUREMENTS: At the day care centers, observations of the care recipients' behavior, affect, and social responses were recorded using a time sampling method. Observations of interactions with Paro for participants in the intervention were also recorded. Blood pressure and salivary cortisol were collected from care recipients before and after sessions at day care. In the home setting, level of cognition, depressive symptoms, neuropsychiatric symptoms, behavioral agitation, and blood pressure were measured at baseline, 6 weeks, and 12 weeks. Hair cortisol measures were collected at baseline and at 6 weeks. RESULTS: Observations showed that Paro significantly improved facial expressions (affect) and communication with staff (social interaction) at the day care centers. Subanalyses showed that care recipients with less cognitive impairment responded significantly better to Paro. There were no significant differences in care recipient dementia symptoms, nor physiological measures between the intervention and control group. CONCLUSION: Paro shows promise in enhancing affective and social outcomes for certain individuals with dementia in a community context. Larger randomized controlled trials in community settings, with longer time frames, are needed to further specify the contexts and characteristics for which Paro is most beneficial.

Effects of tryptophan depletion on selective serotonin reuptake inhibitor-remitted patients with obsessive compulsive disorder.

BACKGROUND: Serotonergic antidepressants are first-line medication therapies for obsessive-compulsive disorder, however it is not known if synaptic serotonin availability is important for selective serotonin reuptake inhibitor efficacy. The present study tested the hypothesis that temporary reduction in central serotonin transmission, through acute tryptophan depletion, would result in an increase in anxiety in selective serotonin reuptake inhibitor-remitted obsessive-compulsive disorder patients. METHODS: Eight patients (four males) with obsessive-compulsive disorder who showed sustained clinical improvement with selective serotonin reuptake inhibitor treatment underwent acute tryptophan depletion in a randomized, double-blind, placebo-controlled, within-subjects design, over two days one week apart. Five hours after consumption of the depleting/sham drink the participants performed a personalized obsessive-compulsive disorder symptom exposure task. Psychological responses were measured using the Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and Visual Analogue Scales. RESULTS: Free plasma tryptophan to large neutral amino acid ratio decreased by 93% on the depletion day and decreased by 1% on the sham day, as anticipated. Psychological rating scores as measured by Visual Analogue Scale showed a significant decrease in perceived control and increase in interfering thoughts at the time of provocation on the depletion day but not on the sham day. A measure of convergent validity, namely Visual Analogue Scale Similar to past, was significantly higher at the time of provocation on both the depletion and sham days. Both the depletion and time of provocation scores for Visual Analogue Scale Anxiety, Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and blood pressure were not significant. CONCLUSIONS: Acute tryptophan depletion caused a significant decrease in perceived control and increase in interfering thoughts at the time of provocation. Acute tryptophan depletion had no effect on the Spielberger State Anxiety Inventory or Visual Analogue Scale Anxiety measures, which suggests that the mechanism of action of selective serotonin reuptake inhibitors may be different to that seen in panic, social anxiety and post-traumatic stress disorder. Successful selective serotonin reuptake inhibitor treatment of obsessive-compulsive disorder may involve the ability of serotonin to switch habitual responding to goal-directed behaviour.