To examine the effect of pulmonary rehabilitation (PR) (exercise and education) or exercise training (ET) on exercise capacity, health-related quality of life (HRQOL), symptoms, frequency of ...exacerbations, and mortality compared with no treatment in adults with bronchiectasis.
Computer-based databases were searched from their inception to February 2016.
Randomized controlled trials of PR or ET versus no treatment in adults with bronchiectasis were included.
Two reviewers independently extracted data and assessed methodologic quality using the Cochrane risk-of-bias tool.
Four trials with 164 participants were included, with variable study quality. Supervised outpatient PR or ET of 8 weeks improved incremental shuttle walk distance (weighted mean difference WMD=67m; 95% confidence interval CI, 52-82m) and disease-specific HRQOL (WMD=-4.65; 95% CI, -6.7 to -2.6 units) immediately after intervention, but these benefits were not sustained at 6 months. There was no effect on cough-related quality of life (WMD=1.3; 95% CI, -0.9 to 3.4 units) or psychological symptoms. PR commenced during an acute exacerbation and continued beyond discharge had no effect on exercise capacity or HRQOL. The frequency of exacerbations over 12 months was reduced with outpatient ET (median, 2 vs 1; P=.013), but PR initiated during an exacerbation had no impact on exacerbation frequency or mortality.
Short-term improvements in exercise capacity and HRQOL were achieved with supervised PR and ET programs, but sustaining these benefits is challenging in people with bronchiectasis. The frequency of exacerbations over 12 months was reduced with ET only.
Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their ...innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations. We find that both channels function as pronounced frequency filters whose transduction efficiencies vary with stimulus frequency, waveform, and duration. We then use numerical simulations and human disease-related point mutations to demonstrate that channel inactivation is the molecular mechanism underlying frequency filtering and further show that frequency filtering is conserved in rapidly adapting mouse DRG neurons. Our results give insight into the potential contributions of Piezos in transducing repetitive mechanical stimuli.
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•Piezo1 and Piezo2 ion channels act as frequency filters of repetitive mechanical stimuli•Frequency filtering is generated by channel inactivation•Human disease-related point mutations in Piezo2 alter frequency filtering•Piezo2 frequency filtering is conserved in rapidly adapting DRG neurons
Lewis et al. examine how Piezo1 and Piezo2 mechanosensitive ion channels transduce repetitive mechanical stimulations. They find that Piezos act as pronounced frequency filters, via a mechanism requiring intact channel inactivation.
Cancer patients who are parents show concerns about their ability to parent following diagnosis, and their adolescent and young adult (AYA) children have a need for improved cancer communication ...within the family. However, psychosocial support for families affected by parental cancer is not routinely available. This study explores the implementation of the Parent Support Worker (PSW) role, as part of a new cross sector model of care to support parent patients, their partners, and AYA children.
Two PSWs, social workers and healthcare staff (n = 26) from three hospitals participated in audio-recorded, semi-structured interviews about implementation of the PSW role. Template Analysis and Normalization Process Theory were used to analyze the interviews. Data on PSW service activity and referrals of AYA to support from a community organization were analyzed using descriptive statistics.
Eleven themes categorized into enablers and barriers of implementation were identified. Regarding acceptability of the role, three enablers (social workers' understanding of the PSW role increasing, easy and prompt access of staff and parent patients to PSWs, satisfaction with the PSW role) and one barrier (communication related confusion and frustration about the PSW role) were identified. Additionally, three enablers (the PSW role fills gaps in parenting-focused support and continuity of care, the PSW role alleviates social workers' workload, negotiation helped to define responsibilities) and one barrier (fear of social work roles to be overtaken by PSWs) for appropriateness of the role were found. Finally, two enablers of feasibility of the role (PSWs and social workers co-managing the work, higher confidence from hospital staff to talk about children in the family) and one barrier (lack of systematic identification and referral processes) were identified. Across hospitals, the number of referrals of AYA children to the community organization increased between 2.7 and 12 times nine months post-introduction of the service.
Established in response to identified gaps in oncology care for parents with cancer, their partners and AYA children, a novel cross-sector model of care was acceptable, appropriate, and feasible. Barriers and enablers to implementation identified in this study need to be considered when designing and implementing similar services.
First-generation microturbines are based on the use of existing materials and proven technology, and with low levels of compressor pressure ratio and modest turbine inlet temperatures, have thermal ...efficiencies approaching 30% for turbogenerators rated up to 100 kW. For such small machines the goal of advancing beyond this level of performance is unlikely to include more complex thermodynamic cycles, but rather will be realised with higher turbine inlet temperatures. Advancing engine performance in this manner has a significant impact on recuperator technology and cost. In the compact heat exchanger field very efficient heat transfer surface geometries have been developed over the last few decades but further improvements perhaps using CFD methods will likely be only incremental. Automated fabrication processes for the manufacture of microturbine recuperators are in place, and on-going developments to facilitate efficient higher temperature operation are primarily focused in the materials area. Based on the assumptions made in this paper it is postulated that in the 100 kW size the maximum thermal efficiency attainable for an all-metallic engine is 35%. To achieve this the recuperator cannot be designed in an isolated manner, and must be addressed in an integrated approach as part of the overall power conversion system. In this regard, temperature limitations as they impact the recuperator and turbine are put into perspective. In this paper there is strong focus on recuperator material selection and cost, including a proposed bi-metallic approach to establish a cost-effective counterflow primary surface recuperator for higher temperature service. If indeed there is a long-term goal to achieve an efficiency of 40% for small microturbines, it can only be projected based on the utilisation of ceramic hot end components. Alas, the high temperature component that has had the minimum development in recent years to realise this goal is the ceramic recuperator, and efforts to remedy this situation need to be undertaken in the near future.
Machine learning has been utilized to predict cancer drug response from multi-omics data generated from sensitivities of cancer cell lines to different therapeutic compounds. Here, we build machine ...learning models using gene expression data from patients' primary tumor tissues to predict whether a patient will respond positively or negatively to two chemotherapeutics: 5-Fluorouracil and Gemcitabine. We focused on 5-Fluorouracil and Gemcitabine because based on our exclusion criteria, they provide the largest numbers of patients within TCGA. Normalized gene expression data were clustered and used as the input features for the study. We used matching clinical trial data to ascertain the response of these patients via multiple classification methods. Multiple clustering and classification methods were compared for prediction accuracy of drug response. Clara and random forest were found to be the best clustering and classification methods, respectively. The results show our models predict with up to 86% accuracy; despite the study's limitation of sample size. We also found the genes most informative for predicting drug response were enriched in well-known cancer signaling pathways and highlighted their potential significance in chemotherapy prognosis. Primary tumor gene expression is a good predictor of cancer drug response. Investment in larger datasets containing both patient gene expression and drug response is needed to support future work of machine learning models. Ultimately, such predictive models may aid oncologists with making critical treatment decisions.
Objective
To describe levels of, and relationships between, distress and psychosocial unmet needs in adolescents and young adults (AYAs) with a family member with cancer.
Methods
Adolescents and ...young adults (12‐24 years old) with a living sibling or parent with cancer participated. Participants completed demographics, the Kessler 10 (K10) distress scale and the Sibling or Offspring Cancer Needs Instruments. Descriptive statistics were obtained for all measures, item‐level frequencies were examined to identify common unmet needs, and relationships between distress and unmet needs were explored.
Results
Average sibling (N = 106) and offspring (N = 256) distress levels were in the high range (K10total = 22‐30), with 29.6% and 31.6% in the very high range (K10total = 31‐50), respectively. Siblings had mean = 19.7 unmet needs (range 0‐45), 66% had ≥10 unmet needs, and 44% of the 45 needs were unmet on average. Offspring had mean = 22.4 unmet needs (range 0‐47), 77% had ≥10 unmet needs, and 48% of the 47 needs were unmet on average. Strong positive correlations were found between K10 distress and the number of sibling/offspring unmet needs (r = 0.599 and r = 0.522, respectively, P = .00).
Conclusions
Australian AYA siblings and offspring impacted by familial cancer experience high levels and numbers of unmet needs and substantial distress. Strong associations were found between increased distress and more unmet needs. Distress levels were comparable to AYAs seeking treatment for mental health issues. Insights into the type and number of needs experienced by AYA siblings and offspring will facilitate development and delivery of targeted, age‐appropriate interventions, and resources for these vulnerable and underserved young people.
Interstitial lung disease (ILD) is characterised by exertional dyspnoea, exercise limitation and reduced quality of life. The role of exercise training in this diverse patient group is unclear. The ...aims of this study were to establish the safety of exercise training in ILD; its effects on exercise capacity, dyspnoea and quality of life; and whether patients with idiopathic pulmonary fibrosis (IPF) had similar responses to those with other types of ILD.
57 subjects with ILD (34 IPF) were randomised to receive 8 weeks of supervised exercise training or weekly telephone support. The 6 min walk distance (6MWD), incremental exercise test, modified Medical Research Council (MRC) dyspnoea score and Chronic Respiratory Disease Questionnaire (CRDQ) were performed at baseline, following intervention and at 6 months.
80% of subjects completed the exercise programme and no adverse events were recorded. The 6MWD increased following training (mean difference to control 35 m, 95% CI 6 to 64 m). A significant reduction in MRC score was observed (0.7 points, 95% CI 0.1 to 1.3) along with improvements in dyspnoea (p = 0.04) and fatigue (p<0.01) on the CRDQ. There was no change in peak oxygen uptake; however, exercise training reduced heart rate at maximum isoworkload (p = 0.01). There were no significant differences in response between those with and without IPF. After 6 months there were no differences between the training and control group for any outcome variable.
Exercise training improves exercise capacity and symptoms in patients with ILD, but these benefits are not sustained 6 months following intervention.
Oligoprogressive disease is a relatively new clinical concept describing progression at only a few sites of metastasis in patients with otherwise controlled widespread disease. In the era of ...well-tolerated targeted treatments, resistance inevitably occurs and overcoming this is a challenge. Local ablative therapy for oligoprogressive disease may allow the continuation of systemic treatments by overcoming the few sub-clones that have developed resistance. Stereotactic body radiotherapy is now frequently used in treating oligometastatic disease using ablative doses with minimally invasive techniques and acceptable toxicity. We discuss the current retrospective clinical evidence base supporting the use of local ablative therapy for oligoprogression in metastatic patients on targeted treatments within multiple tumour sites. As there is currently a lack of published prospective data available, the best management for these patients remains unclear. We discuss current trials in recruitment and the potential advancements in treating this group of patients with stereotactic radiotherapy.
Extremely rare circulating tumor cell (CTC) clusters are both increasingly appreciated as highly metastatic precursors and virtually unexplored. Technologies are primarily designed to detect single ...CTCs and often fail to account for the fragility of clusters or to leverage cluster-specific markers for higher sensitivity. Meanwhile, the few technologies targeting CTC clusters lack scalability. Here, we introduce the Cluster-Wells, which combines the speed and practicality of membrane filtration with the sensitive and deterministic screening afforded by microfluidic chips. The >100,000 microwells in the Cluster-Wells physically arrest CTC clusters in unprocessed whole blood, gently isolating virtually all clusters at a throughput of >25 mL/h, and allow viable clusters to be retrieved from the device. Using the Cluster-Wells, we isolated CTC clusters ranging from 2 to 100+ cells from prostate and ovarian cancer patients and analyzed a subset using RNA sequencing. Routine isolation of CTC clusters will democratize research on their utility in managing cancer.
Periprosthetic femur fracture (PFF) remains a common reason for failure after total hip arthroplasty (THA). For over 10 years, our institution has performed both anterior approach (AA) and ...posterolateral (PL) approaches for primary THA with multiple stem designs. The aim of this study is to determine the 90-day relative risk of PFF with regard to approach and stem design.
A retrospective review of our institutional database was performed on all patients undergoing primary THA from 2007 to 2018 using AA or PL approaches. Five surgeons performing 6309 THAs (AA = 4510; PL = 1799) using single-wedge taper (n = 2417) or fit-and-fill (n = 3892) stems were included. PFF occurring within 90 days of the index procedure were analyzed. Differences in PFF rates, fracture location, stem type, and treatment method were assessed. Comparisons were made using a Cox regression analysis.
The 90-day revision rate for fracture was 0.3%. Clinically significant fractures requiring cerclage cabling, stem change, revision, or open reduction internal fixation occurred in 0.9% of patients (intraoperative = 37, 0.6%; postoperative = 17, 0.3%). Cox regression found PFF risk was significant for female patients (P = .008), patients older than age 65 (P < .01), single-wedge taper stems (P = .05), and for cases with collarless stems (P = .04). Among PFF cases that required surgical intervention, risk factors were female sex, age older than 65, and body mass index under 25 (P < .05). Collarless stems were 2.6 times more likely to result in PFF than collared stems (P = .04). Single-wedge taper stems were 2.3 times more likely to result in PFF than fit-and-fill stems (P = .05). Approach was not found to be an independent risk factor for PFF (P = .85).
Our single-center experience demonstrates the risk of periprosthetic fracture within 90 days of surgery is significantly lower with collared stems and fit-and-fill stem designs. Female sex, age over 65, and body mass index below 25 nearly double the PFF risk. Surgical approach did not influence fracture rates.
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