Web-based physical activity promotion in young people with CF: a randomised controlled trial.

BACKGROUND: Physical activity levels are known to decline following hospitalisation for people with cystic fibrosis (pwCF). However, optimal physical activity promotion strategies are unclear. This study investigated the effect of a web-based application (ActivOnline) in promoting physical activity in young pwCF. METHODS: Multicentre randomised controlled trial with assessor blinding and qualitative evaluation. People with CF (12-35 years) admitted to hospital for a respiratory cause were eligible and randomised to the 12-week ActivOnline intervention (AO) or usual care (UC). The primary outcome was change in device-based time spent in moderate-to-vigorous physical activity (MVPA) from baseline to post-intervention. Follow-up was at 6 months from hospital discharge when qualitative evaluation was undertaken. RESULTS: 107 participants were randomised to AO (n=52) or UC (n=55). Sixty-three participants (59%) contributed to the intention-to-treat analysis. Mean (SD) age was 21 (6) years (n=46, <18 years). At baseline, physical activity levels were high in both groups (AO 102 (52) vs UC 127 (73) min/day). There was no statistically significant difference in MVPA between groups at either timepoint (post-intervention mean difference (95% CI) -14 mins (-45 to 16)). Uptake of the intervention was low with only 40% (n=21) of participants accessing the web application. CONCLUSION: A web-based application, including individualised goal setting, real-time feedback and motivation for behavioural change, was no better than usual care at promoting physical activity in young pwCF following hospital discharge. High levels of baseline physical activity levels in both groups, and limited engagement with the intervention, suggest alternative strategies may be necessary to identify and support young pwCF who would benefit from enhanced physical activity. TRIAL REGISTRATION NUMBER: ACTRN12617001009303, 13 July 13 2017.

Saline at lower tonicity in cystic fibrosis (SALTI-CF) trial comparing 0.9% versus 3% versus 6% nebulised saline.

BACKGROUND: In people with cystic fibrosis (CF), regular nebulisation of 6% or 7% saline improves lung function; however, these concentrations are not always tolerable. Clinically, some CF patients report using lower concentrations of saline to improve tolerability, yet the effects of lower concentrations are unknown. This study therefore aimed to evaluate the relative effectiveness and tolerability of 0.9% versus 3% versus 6% saline nebulised twice daily with an eFlow rapid nebuliser. METHODS: This was a randomised, blinded, placebo-controlled, parallel-group, multicentre study where subjects inhaled 4 mL of 0.9%, 3% or 6% saline twice daily for 16 weeks. The primary outcome was forced expiratory volume in 1 s. The secondary outcomes were: forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC; quality of life; exercise capacity; acquisition or loss of bacterial organisms in expectorated sputum; tolerability of nebulised saline; pulmonary exacerbations; and adverse events. RESULTS: 140 participants were randomised to 0.9% (n=47), 3% (n=48) or 6% (n=45) saline. 134 participants (96%) contributed to the intention-to-treat analysis. 3% saline significantly improved lung function and increased the time to first pulmonary exacerbation compared with 0.9% saline but did not improve quality of life. 6% saline had similar benefits to 3% saline but also significantly improved quality of life compared with 3% saline. Only 6% saline delayed the time to intravenous antibiotics for pulmonary exacerbation. Tolerability and adherence were similar. CONCLUSIONS: Dilution of 6% saline to 3% maintains the benefits for lung function and exacerbation prevention; however, the positive impacts of 6% saline on quality of life and time to i.v. antibiotics for pulmonary exacerbations are lost.

Transition to adult care in cystic fibrosis: The challenges and the structure.

In developed countries, it is projected that there will be a 70% increase in the number of adults living with Cystic Fibrosis (CF) between 2010 and 2025. This shift in demographics highlights the importance of high-quality transition programmes with developmentally appropriate integrated health care services as the individual moves through adolescence to adulthood. Adolescents living with CF face additional and unique challenges that may have long-term impacts on their health, quality of life and life-expectancy. CF specific issues around socially challenging symptoms, body image, reproductive health and treatment burden differentiate people with CF from their peers and require clinicians to identify and address these issues during the transition process. This review provides an overview of the health, developmental and psychosocial challenges faced by individuals with CF, their guardians and health care teams considering the fundamental components and tools that are required to build a transition programme that can be tailored to suit individual CF clinics.

A web-based intervention to promote physical activity in adolescents and young adults with cystic fibrosis: protocol for a randomized controlled trial.

BACKGROUND: Regular participation in physical activity by people with cystic fibrosis (CF) promotes positive clinical and health outcomes including reduced rate of decline in lung function, fewer hospitalizations and greater wellbeing. However adherence to exercise and activity programs is low, in part due to the substantial daily therapy burden for young people with CF. Strict infection control requirements limit the role of group exercise programs that are commonly used in other clinical groups. Investigation of methods to promote physical activity in this group has been limited. The Active Online Physical Activity in Cystic fibrosis Trial (ActionPACT) is an assessor-blinded, multi-centre, randomized controlled trial designed to compare the efficacy of a novel web-based program (ActivOnline) compared to usual care in promoting physical activity participation in adolescents and young adults with CF. METHODS: Adolescents and young adults with CF will be recruited on discharge from hospital for a respiratory exacerbation. Participants randomized to the intervention group will have access to a web-based physical activity platform for the 12-week intervention period. ActivOnline allows users to track their physical activity, set goals, and self-monitor progress. All participants in both groups will be provided with standardised information regarding general physical activity recommendations for adolescents and young adults. Outcomes will be assessed by a blinded assessor at baseline, after completion of the intervention, and at 3-months followup. Healthcare utilization will be assessed at 12 months from intervention completion. The primary outcome is change in moderate-to-vigorous physical activity participation measured objectively by accelerometry. Secondary outcomes include aerobic fitness, health-related quality of life, anxiety and depression and sleep quality. DISCUSSION: This trial will establish whether a web-based application can improve physical activity participation more effectively than usual care in the period following hospitalization for a respiratory exacerbation. The web-based application under investigation can be made readily and widely available to all individuals with CF, to support physical activity and exercise participation at a time and location of the user's choosing, regardless of microbiological status. TRIAL REGISTRATION: Clinical trial registered on July 13, 2017 with the Australian and New Zealand Clinical Trials Register at (ACTRN12617001009303).

Effects of a compression garment on sensory feedback transmission in the human upper limb.

Compression apparel is popular in both medical and sport performance settings. Perceived benefits are suggested to include changes in sensory feedback transmission caused by activation of mechanoreceptors. However, little is known about effects of compression apparel on sensorimotor control. Our purpose was to mechanistically examine whether compression apparel modulates sensory feedback transmission and reaching accuracy in the upper limb. Two experiments were completed under CONTROL and COMPRESSION (sleeve applied across the elbow joint) conditions. M-waves and H-reflexes were elicited by stimulating the median nerve and were recorded via surface electromyography (EMG). In experiment 1, H-reflexes and M-H recruitment curves were assessed at REST, during wrist flexion (10% EMGmax), and during a cutaneous conditioning of the superficial radial (SR) or distal median (MED) nerve. Cutaneous reflexes were elicited during 10% wrist flexion via stimulation of SR or MED. In experiment 2, unconditioned H-reflex measures were assessed at rest, during arm cycling, and during a discrete reaching task. Results indicate that compression apparel modulates spinal cord excitability across multiple sensory pathways and movement tasks. Interestingly, there was a significant improvement in reaching accuracy while wearing the compression sleeve. Taken together, the compression sleeve appears to increase precision and sensitivity around the joint where the sleeve is applied. Compression apparel may function as a "filter" of irrelevant mechanoreceptor information allowing for optimal task-related sensory information to enhance proprioception. NEW & NOTEWORTHY Wearing a customized compression sleeve was shown to alter the excitability of multiple pathways within the central nervous system regardless of conditioning input or movement task and was accompanied by improved accuracy of reaching movements and determination of movement end point. Compression apparel may assist as a type of "filter function" of tonic and nonspecific mechanoreceptor information leading to increased precision and movement sensitivity around the joint where compression is applied.

Moving epidemic method (MEM) applied to virology data as a novel real time tool to predict peak in seasonal influenza healthcare utilisation. The Scottish experience of the 2017/18 season to date.

Scotland observed an unusual influenza A(H3N2)-dominated 2017/18 influenza season with healthcare services under significant pressure. We report the application of the moving epidemic method (MEM) to virology data as a tool to predict the influenza peak activity period and peak week of swab positivity in the current season. This novel MEM application has been successful locally and is believed to be of potential use to other countries for healthcare planning and building wider community resilience.

Excess all-cause and influenza-attributable mortality in Europe, December 2016 to February 2017.

Since December 2016, excess all-cause mortality was observed in many European countries, especially among people aged ≥ 65 years. We estimated all-cause and influenza-attributable mortality in 19 European countries/regions. Excess mortality was primarily explained by circulation of influenza virus A(H3N2). Cold weather snaps contributed in some countries. The pattern was similar to the last major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in line with the early influenza season start.

A randomised trial of hypertonic saline during hospitalisation for exacerbation of cystic fibrosis.

BACKGROUND: The mucoactive effects of hypertonic saline should promote exacerbation resolution in people with cystic fibrosis (CF). OBJECTIVES: To determine the effects of hypertonic saline inhalation during hospitalisation for exacerbation of CF on length of stay, lung function, symptoms, oxygenation, exercise tolerance, quality of life, bacterial load and time to next hospitalisation. METHODS: 132 adults with an exacerbation of CF were randomised to inhale three nebulised doses a day of either 4 mL 7% saline or a taste-masked control of 0.12% saline, throughout the hospital admission. The primary outcome measure was length of hospital stay. RESULTS: All participants tolerated their allocated saline solution. There was no significant difference in length of stay, which was 12 days in the hypertonic saline group and 13 days in controls, with a mean between-group difference (MD) of 1 day (95% CI 0 to 2). The likelihood of regaining pre-exacerbation FEV1 by discharge was significantly higher in the hypertonic saline group (75% vs 57%), and the number needed to treat was 6 (95% CI 3 to 65). On a 0-100 scale, the hypertonic saline group had significantly greater reduction in symptom severity than the control group at discharge in sleep (MD=13, 95% CI 4 to 23), congestion (MD=10, 95% CI 3 to 18) and dyspnoea (MD=8, 95% CI 1 to 16). No significant difference in time to next hospitalisation for a pulmonary exacerbation was detected between groups (HR=0.86 (CI 0.57 to 1.30), p=0.13). Other outcomes did not significantly differ. CONCLUSIONS: Addition of hypertonic saline to the management of a CF exacerbation did not reduce the length of hospital stay. Hypertonic saline speeds the resolution of exacerbation symptoms and allows patients to leave hospital with greater symptom resolution. TRIAL REGISTRATION NUMBER: ACTRN12605000780651.

Lyn deficiency leads to increased microbiota-dependent intestinal inflammation and susceptibility to enteric pathogens.

The Lyn tyrosine kinase governs the development and function of various immune cells, and its dysregulation has been linked to malignancy and autoimmunity. Using models of chemically induced colitis and enteric infection, we show that Lyn plays a critical role in regulating the intestinal microbiota and inflammatory responses as well as protection from enteric pathogens. Lyn(-/-) mice were highly susceptible to dextran sulfate sodium (DSS) colitis, characterized by significant wasting, rectal bleeding, colonic pathology, and enhanced barrier permeability. Increased DSS susceptibility in Lyn(-/-) mice required the presence of T but not B cells and correlated with dysbiosis and increased IFN-γ(+) and/or IL-17(+) colonic T cells. This dysbiosis was characterized by an expansion of segmented filamentous bacteria, associated with altered intestinal production of IL-22 and IgA, and was transmissible to wild-type mice, resulting in increased susceptibility to DSS. Lyn deficiency also resulted in an inability to control infection by the enteric pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium. Lyn(-/-) mice exhibited profound cecal inflammation, bacterial dissemination, and morbidity following S. Typhimurium challenge and greater colonic inflammation throughout the course of C. rodentium infection. These results identify Lyn as a key regulator of the mucosal immune system, governing pathophysiology in multiple models of intestinal disease.

Physiotherapy for cystic fibrosis in Australia and New Zealand: A clinical practice guideline.

Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non-invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence-based physiotherapy care to people with CF in Australia and New Zealand.

Hsp27 regulates EGF/ß-catenin mediated epithelial to mesenchymal transition in prostate cancer.

Increased expression of the molecular chaperone Hsp27 is associated with the progression of prostate cancer (PCa) to castration-resistant disease, which is lethal due to metastatic spread of the prostate tumor. Metastasis requires epithelial to mesenchymal transition (EMT), which endows cancer cells with the ability to disseminate from the primary tumor and colonize new tissue sites. A wide variety of secreted factors promote EMT, and while overexpression and constitutive activation of epidermal growth factor (EGF) signaling is associated with poor prognosis of PCa, a precise role of EGF in PCa progression to metastasis remains unclear. Here, we show that Hsp27 is required for EGF-induced cell migration, invasion and MMPs activity as well as the expression of EMT markers including Fibronectin, Vimentin and Slug with concomitant decrease of E-cadherin. Mechanistically, we found that Hsp27 is required for EGF-induced AKT and GSK3ß phosphorylation and ß-catenin nuclear translocation. Moreover, silencing Hsp27 decreases EGF dependent phosphorylation of ß-catenin on tyrosine 142 and 654, enhances ß-catenin ubiquitination and degradation, prevents ß-catenin nuclear translocation and binding to the Slug promoter. These data suggest that Hsp27 is required for EGF-mediated EMT via modulation of the ß-catenin/Slug signaling pathway. Together, our findings underscore the importance of Hsp27 in EGF induced EMT in PCa and highlight the use of Hsp27 knockdown as a useful strategy for patients with advanced disease.

Beyond immune checkpoint blockade: new approaches to targeting host-tumor interactions in prostate cancer: report from the 2014 Coffey-Holden prostate cancer academy meeting.

INTRODUCTION: The 2014 Coffey-Holden Prostate Cancer Academy Meeting, held in La Jolla, CA from June 26 to 29, 2014, was themed: "Beyond Immune Checkpoint Blockade: New Approaches to Targeting Host-Tumor Interactions in Prostate Cancer." METHODS: Sponsored by the Prostate Cancer Foundation (PCF), this annual, invitation-only meeting is structured as an action-tank, and brought together 72 investigators with diverse academic backgrounds to discuss the most relevant topics in the fields of prostate cancer immunotherapy and the tumor microenvironment. RESULTS: The questions addressed at the meeting included: mechanisms underlying the successes and failures of prostate cancer immunotherapies, how to trigger an effective immune response against prostate cancer, the tumor microenvironment and its role in therapy resistance and tumor metastasis, clinically relevant prostate cancer mouse models, how host-tumor interactions affect current therapies and tumor phenotypes, application of principles of precision medicine to prostate cancer immunotherapy, optimizing immunotherapy clinical trial design, and complex multi-system interactions that affect prostate cancer and immune responses including the effects of obesity and the potential role of the host microbiome. DISCUSSION: This article highlights the most significant recent progress and unmet needs that were discussed at the meeting toward the goal of speeding the development of optimal immunotherapies for the treatment of prostate cancer.

Obstetric fistula in low-resource countries: an under-valued and under-studied problem--systematic review of its incidence, prevalence, and association with stillbirth.

BACKGROUND: Obstetric fistula (OF) is a serious consequence of prolonged, obstructed labor in settings where emergency obstetric care is limited, but there are few reliable, population-based estimates of the rate of OF. Stillbirth (SB) is another serious consequence of prolonged, obstructed labor, yet the frequency of SB in women with OF is poorly described. Here, we review these data. METHODS: We searched electronic databases and grey literature for articles on OF in low-resource countries published between January 1, 1995, and November 16, 2014, and selected for inclusion 19 articles with original population-based OF incidence or prevalence data and 44 with reports of frequency of SB associated with OF. RESULTS: OF estimates came from medium- and low-HDI countries in South Asia and Africa, and varied considerably; incidence estimates ranged from 0 to 4.09 OF cases per 1000 deliveries, while prevalence estimates were judged more prone to bias and ranged from 0 to 81.0 OF cases per 1000 women. Reported frequency of SB associated with OF ranged from 32.3 % to 100 %, with estimates from the largest studies around 92 %. Study methods and quality were inconsistent. CONCLUSIONS: Reliable data on OF and associated SB in low-resource countries are lacking, underscoring the relative invisibility of these issues. Sound numbers are needed to guide policy and funding responses to these neglected conditions of poverty.

Prevalence and impact of persistent symptoms following SARS-CoV-2 infection among healthcare workers: A cross-sectional survey in the SIREN cohort.

INTRODUCTION: Following SARS-CoV-2 infection, some patients experience a range of long-lasting symptoms, with a specific burden on their lives and ability to work. AIM: We describe the prevalence and impact of persistent symptoms pre-/post-vaccination in SIREN study participants. METHODS: A cross-sectional study of SARS-CoV-2 positive participants was carried out within SIREN, a frequently tested UK healthcare worker cohort with vaccination and demographic data available. Participants with a SARS-CoV-2 positive PCR or anti-SARS-CoV-2 sample between 01 March 2020 and 31 September 2022 were asked via a questionnaire about symptoms and days absent from work following infection. Responses were excluded if infection dates were inconsistent with study records or missing key data. Symptom type/duration and whether infection occurred pre-/post-vaccination and during which variant period were described. Logistic regression was used to estimate factors associated with persistent symptoms (>12 weeks), adjusting for vaccination and demographic factors. The median days absent from work were also determined. RESULTS: Of 16,599 invitations, 6677 participants responded, and 5053 were included in the analysis. The prevalence of persistent symptoms (symptoms lasting over 12 weeks) differed by infection episode; highest for first infections (32.7%; 1557/4767) compared to second (21.6%; 214/991) and third infections (21.6%; 16/74). Most frequently reported symptoms were fatigue, tiredness, shortness of breath and difficulty concentrating. A higher prevalence of persistent symptoms was reported during the Wild-type variant period compared to the other variant periods (52.9% Wild-type vs. 20.7% Omicron, for any symptom reported during their first infection). Overall, persistent symptoms were higher among unvaccinated participants (unvaccinated 38.1% vs vaccinated 22.0%). Multivariable analysis showed that participants were less likely to report persistent symptoms in infections occurring after vaccination compared to those with an infection before vaccination in the Alpha/Delta and Omicron periods (Alpha/Delta: adjusted Odds Ratio (aOR) 0.66, CI 95% 0.51-0.87, p = aOR 0.07, CI 95% 0.01-0.65, p = 0.02). About half of participants reported that their persistent symptoms impacted their day-to-day (51.8%) and work-related (42.1%) activities 'a little', and 24.0% and 14.4% reported that the impact was 'A lot'. 8.9% reported they had reduced their working hours, and 13.9% had changed their working pattern. DISCUSSION: Persistent symptoms were frequent in our cohort, and there was a reduction in symptom duration in those with multiple infection episodes during later variant periods and post-vaccination. The impact of persistent symptoms resulting in reducing working hours or adjusting working patterns has important implications for workforce resilience. UK healthcare workers were highly exposed during the pandemic, demonstrating a significant burden.

Is there a correlation between breast cancer molecular subtype using receptors as surrogates and mammographic appearance?

BACKGROUND: The identification of distinct molecular subtypes has changed breast cancer management. The correlation between mammographic appearance and molecular subtype for invasive breast cancer has not been extensively studied. METHODS: A retrospective review of our prospectively collected database was performed to evaluate the mammographic appearance and molecular subtypes of all cases of invasive breast cancers diagnosed between 2003 and 2010. RESULTS: There were 985 cases of invasive breast cancer with complete data on receptor status and mammographic appearance. The most common mammographic finding was a mass (61 %), and the most common molecular subtype was ER/PR positive, HER2 negative (71 %). On univariate analysis, race, stage, and histology were all significantly associated with molecular subtype. On multivariate analysis, the luminal molecular type was associated with architectural distortion [odds ratio (OR) 4.3, 95 % CI 1.3-14.1]; HER2 positive cancers, either with or without ER/PR expression, were more likely to be associated with mammographic calcifications (OR 2.8 and 3.1, respectively; 95 % CI 1.7-4.8 and 1.7-5.5); and triple negative cancers were most likely to be associated with a mammographic mass (OR 2.5; 95 % CI 1.4-4.4). CONCLUSIONS: We observed several characteristic associations between molecular subtype and mammographic appearance. Improved understanding of these associations may help guide clinical decision making and provide information about underlying tumor biology.

Decreasing Clostridium difficile infections in surgery: impact of a practice bundle incorporating a resident rounding protocol.

INTRODUCTION: Clostridium difficile (CD) infection is a significant health problem. A new systems approach was introduced to reduce the risk of hospital-acquired CD infection (HA-CD) at our institution. We hypothesized that a practice bundle, including a protocol to limit patient exposures during house staff rounding, would decrease HA-CD infections. METHODS: Over a three-year period, 39,093 cases (17,145 inpatients) admitted to the surgical services were reviewed. Cases were reviewed for patient demographics, antibiotic exposures, compliance with antibiotic prophylaxis guidelines, and surgical infections. A resident rounding protocol was developed to limit patient exposures. The program bundle also included a hand washing initiative, maintaining gastric acidity, and antibiotic stewardship. RESULTS: After implementation of the bundle, the average monthly HA-CD infection rate in surgical patients decreased from 4.13 + 2.6 cases to 1.93 + 1.6 cases, p = 0.03. The overall rate of HA-CD infections for surgical cases decreased 41% from 2.8 cases/1,000 patient days to 1.8 cases/1,000 patient-days. CONCLUSIONS: Bundled programs designed to reduce patient risk by controlling exposure to both environmental and carrier sources of CD can reduce hospital-acquired CD infections.

Referral for Cardiac Amyloidosis in Patients Who Underwent Transcatheter Aortic Valve Replacement: Results of the Quality Outcome Project.

Background Transthyretin cardiac amyloidosis (ATTR) is an important comorbidity present in severe aortic stenosis (AS). The purpose of this study was to raise awareness of ATTR in patients who underwent transcatheter aortic valve replacement (TAVR) for severe AS among healthcare providers and patients. Methodology We reviewed 197 consecutive TAVR cases performed from 2019 to 2020. Adapting predefined high-risk features for ATTR based on prior literature, we contacted the patients to discuss our clinical suspicion of ATTR and offered a referral to a cardiac amyloid specialist. Results We identified 125 (69.4%) patients who had high-risk features of ATTR. Of the 105 patients contacted, 44 patients agreed to referral, 46 patients were not able to be contacted after several attempts, and 15 patients declined referral. Of the 44 patients who agreed to the referral, 20 patients completed the evaluation for cardiac amyloidosis, all of whom were negative for transthyretin and light-chain cardiac amyloidosis. Conclusions Our attempt to detect ATTR in prior TAVR patients was unsuccessful two to three years post-TAVR. We believe that early detection of cardiac amyloidosis close to the timing of TAVR is important and the most effective means.

Correction: Referral for Cardiac Amyloidosis in Patients Who Underwent Transcatheter Aortic Valve Replacement: Results of the Quality Outcome Project.

[This corrects the article DOI: 10.7759/cureus.45024.].