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The Caliciviridae family, comprising positive-sense RNA viruses, is characterised by its non-enveloped, small virions, broad host range, and notable tendency for host switching. These viruses are primarily associated with gastroenteric disease, though they can lead to haemorrhagic or respiratory infections. Our study employed a metagenomics analysis of faecal samples from stoats (Mustela erminea), identifying two novel calicivirus species, named stoat vesivirus and stoat valovirus. Stoat vesivirus was identified in three samples (ST008, ST006, ST004), exhibiting a genome wide nucleotide identity of approximately 92â%. The complete coding sequences of these samples were 8471 (ST004) and 8322 (ST006) nucleotides in length, respectively. Each comprised three open reading frames (ORF), closely resembling the Vesivirus mink calicivirus (China/2/2016), with 70-72â% similarity in ORF1, 61-62â% in ORF2 and 71â% in ORF3. Phylogenetic analysis robustly supported stoat vesivirus as belonging within the Vesivirus genus. The second calivicirus (stoat valovirus), detected solely in sample ST008, was 6527 nucleotides in length and with complete coding sequences present. It shared highest similarity with St-Valérien swine virus and marmot norovirus HT16, showing 39.5 and 38.8â% protein identity with ORF1 and 43.3 and 42.9â% for VP1. Stoat valovirus is borderline for meeting the ICTV criteria for a new genus, demonstrating 60â% divergence in ORF1 compared to the other valovirus', however it clusters basally within the Valovirus genus, supporting leaving it included in this genus.
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BACKGROUND: Pulmonary rehabilitation (PR) is accepted as standard care for individuals with COPD. We conducted an international, multi-centred randomized controlled trial (RCT) to determine if adding balance training to PR would reduce the incidence of falls in people with COPD. While there have been many trials investigating the effectiveness of PR, few have involved international collaboration. Successful execution of rehabilitation trials requires a significant investment of time, staffing, and resources. With the recent completion of the Balance Training for Fall Reduction in COPD RCT, we report on the design, implementation, and execution of our trial using project management phases. We also highlight our lessons learned for consideration in future multi-centre rehabilitation trials. METHODS: This was a retrospective review of the planning, preparation, timelines, and personnel training involved in the execution of this study using four of the five project management phases described by Farrell et al. in 2010: (1) initiation, (2) planning, (3) execution, and (4) monitoring and controlling. We report descriptive statistics as percentages and counts and summarize our lessons learned. RESULTS: Ten outpatient PR programs in three continents participated. Thirty-one personnel worked on the trial across all sites. Enrolment began in January 2017 and was suspended in March 2020 due to the COVID-19 pandemic. Approximately 1275 patients were screened, 455 (36%) were eligible, 258 (57%) consented, 243 (53%) participated, and 130 (61%) completed the 12-month follow-up assessment. Lessons learned through our experience included (1) ensuring awareness of funder policies and considering the impact on collaborating sites; (2) preparing for the possibility of human resource and program disruptions; (3) anticipating site dropout and having a contingency plan in place; (4) planning and monitoring process measure data before, during, and after trial initiation; (5) ensuring frequent and consistent communication with and between collaborating sites; (6) maximizing features of database platform to ensure data set completeness and controlled data access; and (7) identifying strategies for increasing patient engagement in a high-demand study. CONCLUSIONS: We identify seven lessons learned through our experience conducting an international, multicentre rehabilitation-based RCT. These lessons can provide guidance to other trialists conducting studies with similar logistics and may assist with future trial planning and implementation.
Subject(s)
Accidental Falls , Postural Balance , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/rehabilitation , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Accidental Falls/prevention & control , Retrospective Studies , Incidence , Treatment Outcome , Multicenter Studies as Topic , Research Design , Randomized Controlled Trials as Topic , Exercise Therapy/methods , Time FactorsABSTRACT
INTRODUCTION: This review quantifies the mean treatment effect of exercise-based interventions on balance and falls risk in people with COPD. METHODS: A structured search strategy (2000-2023) was applied to eight databases to identify studies evaluating the impact of exercise-based interventions (≥14â days in duration) on balance or falls in people with COPD. Pooled mean treatment effects (95% confidence intervals (CIs), 95% prediction intervals (PIs)) were calculated for outcomes reported in five or more studies. Inter-individual response variance and the promise of behaviour change techniques (BCTs) were explored. RESULTS: 34 studies (n=1712) were included. There were greater improvements in balance post intervention compared to controls for the Berg Balance Scale (BBS) (mean 2.51, 95% CI 0.22-4.80, 95% PI -4.60-9.63), Timed Up and Go (TUG) test (mean -1.12â s, 95% CI -1.69-â -0.55â s, 95% PI -2.78-0.54â s), Single-Leg Stance (SLS) test (mean 3.25â s, 95% CI 2.72-3.77â s, 95% PI 2.64-3.86â s) and Activities-specific Balance Confidence (ABC) scale (mean 8.50%, 95% CI 2.41-14.58%, 95% PI -8.92-25.92%). Effect on falls remains unknown. Treatment effects were larger in male versus mixed-sex groups for the ABC scale and SLS test, and in balance training versus other exercise-based interventions for the BBS and TUG test. Falls history was not associated with changes in balance. Meta-analysis of individual response variance was not possible and study-level results were inconclusive. Eleven promising BCTs were identified (promise ratio ≥2). CONCLUSION: Evidence for the effect of exercise-based interventions eliciting clinically important improvements in balance for people with COPD is weak, but targeted balance training produces the greatest benefits. Future exercise interventions may benefit from inclusion of the identified promising BCTs.
Subject(s)
Accidental Falls , Exercise Therapy , Postural Balance , Pulmonary Disease, Chronic Obstructive , Humans , Accidental Falls/prevention & control , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Exercise Therapy/methods , Male , Treatment Outcome , Female , Aged , Risk Factors , Middle Aged , Recovery of Function , Lung/physiopathologyABSTRACT
BACKGROUND: Dupuytren's contractures (DC) are fibrous cords under the skin of the hand that cause one or more fingers to curl gradually and irreversibly towards the palm. These contractures are usually painless but can cause a loss of hand function. Two treatments for Dupuytren's contractures are widely used within the National Health Service (NHS) in the UK: removal of the contractures via surgery (limited fasciectomy) and division of the contractures via a needle inserted through the skin (needle fasciotomy). This study aims to establish the clinical and cost-effectiveness of needle fasciotomy (NF) versus limited fasciectomy (LF) for the treatment of DC in the NHS, in terms of patient-reported hand function and resource utilisation. METHODS/DESIGN: Hand-2 is a national multi-centre, two-arm, parallel-group randomised, non-inferiority trial. Patients will be eligible to join the trial if they are aged 18 years or older, have at least one previously untreated finger with a well-defined Dupuytren's contracture of 30° or greater that causes functional problems and is suitable for treatment with either LF or NF. Patients with a contracture of the distal interphalangeal joint only are ineligible. Eligible consenting patients will be randomised 1:1 to receive either NF or LF and will be followed up for 24 months post-treatment. A QuinteT Recruitment Intervention will be used to optimise recruitment. The primary outcome measure is the participant-reported assessment of hand function, assessed by the Hand Health Profile of the Patient Evaluation Measure (PEM) questionnaire at 12 months post-treatment. Secondary outcomes include other patient-reported measures, loss of finger movement, and cost-effectiveness, reported over the 24-month post-treatment. Embedded qualitative research will explore patient experiences and acceptability of treatment at 2 years post-surgery. DISCUSSION: This study will determine whether treatment with needle fasciotomy is non-inferior to limited fasciectomy in terms of patient-reported hand function at 12 months post-treatment. TRIAL REGISTRATION: International Standard Registered Clinical/soCial sTudy ISRCTN12525655. Registered on 18th September 2020.
Subject(s)
Cost-Benefit Analysis , Dupuytren Contracture , Fasciotomy , Multicenter Studies as Topic , Needles , Dupuytren Contracture/surgery , Dupuytren Contracture/physiopathology , Humans , Treatment Outcome , Equivalence Trials as Topic , Recovery of Function , Fingers/surgery , United Kingdom , Time Factors , Patient Reported Outcome MeasuresABSTRACT
BACKGROUND: Patients newly initiated on opioids (OP), benzodiazepines (BZD), and antipsychotics (AP) during hospitalization are often prescribed these on discharge. Implications of this practice on outcomes remains unexplored. OBJECTIVE: To explore the prevalence and risk factors of new initiation of select OP, BZD and AP among patients requiring in-patient stays. Test the hypothesis that new prescriptions are associated with higher odds of readmission or death within 28 days of discharge. DESIGN: Single center retrospective cohort study. SETTING AND PARTICIPANTS: Patients admitted to a tertiary-level medical center with either a primary diagnosis of RT-PCR positive for COVID-19 or high index of clinical suspicion thereof. INTERVENTION: None. MAIN OUTCOME AND MEASURES: Exposure was the new initiation of select common OP, BZD, and AP which were continued on hospital discharge. Outcome was a composite of 28-day readmission or death following index admission. Multivariable logistic regression was used to assess patient mortality or readmission within 28 days of discharge associated with new prescriptions at discharge. RESULTS: One thousand three hundred and nineteen patients were included in the analysis. 11.3% (149/1319) were discharged with a new prescription of select OP, BZD, or AP either alone or in combination. OP (110/149) were most prescribed followed by BZD (41/149) and AP (22/149). After adjusting for unbalanced confounders, new prescriptions (adjusted odds ratio: 2.44, 95% confidence interval: 1.42-4.12; p = .001) were associated with readmission or death within 28 days of discharge. One in nine patients admitted with a diagnosis of COVID-19 or high clinical suspicion thereof were discharged with a new prescription of either OP, BZD or AP. New prescriptions were associated with higher odds of 28-day readmission or death. Strengthening medication reconciliation processes focused on these classes may reduce avoidable harm.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) increases fall risk, but consensus is lacking on suitable balance measures for fall risk screening in this group. We aimed to evaluate the reliability and validity of balance measures for fall risk screening in community-dwelling older adults with COPD. METHODS: In a secondary analysis of two studies, participants, aged ≥60 years with COPD and 12-month fall history or balance issues were tracked for 12-month prospective falls. Baseline balance measures - Brief Balance Evaluation Systems Test (Brief BESTest), single leg stance (SLS), Timed Up and Go (TUG), and TUG Dual-Task (TUG-DT) test - were assessed using intra-class correlation (ICC2,1) for reliability, Pearson/Spearman correlation with balance-related factors for convergent validity, t-tests/Wilcoxon rank-sum tests with fall-related and disease-related factors for known-groups validity, and area under the receiver operator characteristic curve (AUC) for predictive validity. RESULTS: Among 174 participants (73 ± 8 years; 86 females) with COPD, all balance measures showed excellent inter-rater and test-retest reliability (ICC2,1 = 0.88-0.97) and moderate convergent validity (r = 0.34-0.77) with related measures. Brief BESTest and SLS test had acceptable known-groups validity (p < 0.05) for 12-month fall history, self-reported balance problems, and gait aid use. TUG test and TUG-DT test discriminated between groups based on COPD severity, supplemental oxygen use, and gait aid use. All measures displayed insufficient predictive validity (AUC<0.70) for 12-month prospective falls. CONCLUSION: Though all four balance measures demonstrated excellent reliability, they lack accuracy in prospectively predicting falls in community-dwelling older adults with COPD. These measures are best utilized within multi-factorial fall risk assessments for this population.
Subject(s)
Accidental Falls , Independent Living , Postural Balance , Pulmonary Disease, Chronic Obstructive , Humans , Accidental Falls/prevention & control , Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Female , Postural Balance/physiology , Male , Reproducibility of Results , Longitudinal Studies , Risk Assessment/methods , Aged, 80 and over , Middle Aged , Mass Screening/methods , Prospective Studies , Risk FactorsABSTRACT
Assessment of self-conscious emotions is important to develop tailored interventions for people with chronic obstructive pulmonary disease (COPD). Previous instruments have largely been developed for mental health populations. The Self-Conscious Emotions in COPD Questionnaire was the first instrument to assess self-conscious emotions in people with COPD, but it was only available in English. The aim was to translate the Self-Conscious Emotions in COPD Questionnaire into Swedish and to evaluate its psychometric properties and internal structure in a Swedish context. The translation process included forward and backward translation, a multidisciplinary meeting, assessment of content validity, and cognitive interviews. The translated instrument was tested in a sample of 173 people with COPD between September 2021 and September 2022. Parallel analysis (PA), exploratory factor analysis (EFA), and test-retest reliability was performed. The content validity index (CVI) for the instrument was 0.88. Based on the PA, an EFA with a two-factor solution was conducted, with a high Cronbach's alpha (0.786-0.821), and one item about self-blame was excluded. The two factors were labelled: The burden of living with a disability and The desire to hide vulnerability. Test-retest reliability showed no difference between scale scores on factor or item level, except for one item. The Swedish Self-Conscious Emotions in COPD showed good validity and reliability. One item was excluded from the two subscales, indicating that the instrument needs to be further developed to cover the concept of self-blame. The instrument is expected to be a valuable tool for assessing self-conscious emotions in people with COPD.
Subject(s)
Emotions , Psychometrics , Pulmonary Disease, Chronic Obstructive , Translations , Humans , Pulmonary Disease, Chronic Obstructive/psychology , Pulmonary Disease, Chronic Obstructive/physiopathology , Psychometrics/methods , Sweden , Surveys and Questionnaires , Male , Female , Aged , Reproducibility of Results , Middle Aged , Factor Analysis, StatisticalABSTRACT
Successful social interactions between mothers and children are hypothesised to play a significant role in a child's social, cognitive and language development. Earlier research has confirmed, through structured experimental paradigms, that these interactions could be underpinned by coordinated neural activity. Nevertheless, the extent of neural synchrony during real-life, ecologically valid interactions between mothers and their children remains largely unexplored. In this study, we investigated mother-child inter-brain synchrony using a naturalistic free-play paradigm. We also examined the relationship between neural synchrony, verbal communication patterns and personality traits to further understand the underpinnings of brain synchrony. Twelve children aged between 3 and 5 years old and their mothers participated in this study. Neural synchrony in mother-child dyads were measured bilaterally over frontal and temporal areas using functional Near Infra-red Spectroscopy (fNIRS) whilst the dyads were asked to play with child-friendly toys together (interactive condition) and separately (independent condition). Communication patterns were captured via video recordings and conversational turns were coded. Compared to the independent condition, mother-child dyads showed increased neural synchrony in the interactive condition across the prefrontal cortex and temporo-parietal junction. There was no significant relationship found between neural synchrony and turn-taking and between neural synchrony and the personality traits of each member of the dyad. Overall, we demonstrate the feasibility of measuring inter-brain synchrony between mothers and children in a naturalistic environment. These findings can inform future study designs to assess inter-brain synchrony between parents and pre-lingual children and/or children with communication needs.
Subject(s)
Brain , Spectroscopy, Near-Infrared , Humans , Child, Preschool , Spectroscopy, Near-Infrared/methods , Prefrontal Cortex , Brain Mapping/methods , Mother-Child Relations/psychologyABSTRACT
Repeat spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into new hosts has highlighted the critical role of cross-species transmission of coronaviruses and establishment of new reservoirs of virus in pandemic and epizootic spread of coronaviruses. Species particularly susceptible to SARS-CoV-2 spillover include Mustelidae (mink, ferrets and related animals), cricetid rodents (hamsters and related animals), felids (domestic cats and related animals) and white-tailed deer. These predispositions led us to screen British wildlife with sarbecovirus-specific quantitative PCR and pan coronavirus PCR assays for SARS-CoV-2 using samples collected during the human pandemic to establish if widespread spillover was occurring. Fourteen wildlife species (n=402) were tested, including: two red foxes (Vulpes vulpes), 101 badgers (Meles meles), two wild American mink (Neogale vison), 41 pine marten (Martes martes), two weasels (Mustela nivalis), seven stoats (Mustela erminea), 108 water voles (Arvicola amphibius), 39 bank voles (Myodes glareolous), 10 field voles (Microtus agrestis), 15 wood mice (Apodemus sylvaticus), one common shrew (Sorex aranaeus), two pygmy shrews (Sorex minutus), two hedgehogs (Erinaceus europaeus) and 75 Eurasian otters (Lutra lutra). No cases of SARS-CoV-2 were detected in any animals, but a novel minacovirus related to mink and ferret alphacoronaviruses was detected in stoats recently introduced to the Orkney Islands. This group of viruses is of interest due to pathogenicity in ferrets. The impact of this virus on the health of stoat populations remains to be established.
Subject(s)
Alphacoronavirus , COVID-19 , Deer , Otters , Viruses , Animals , Humans , Cats , Mice , Animals, Wild , Ferrets , Mink , SARS-CoV-2/genetics , COVID-19/veterinary , ArvicolinaeABSTRACT
Background: Higher education institutions (HEIs) developed and implemented a mandatory COVID-19 vaccination policy to facilitate vaccine acceptance and vaccination among universities' staff and students. However, little is known about influences of the mandatory vaccination policy on health science students at a university and they tend to result in vaccine hesitancy. Aim: To explore the influences of the mandatory COVID-19 vaccine policy on health sciences students' vaccine acceptance at HEIs in South Africa. Setting: The study was conducted in one of the universities in the Western Cape Province, South Africa. Methods: An interpretive qualitative exploratory-descriptive research was conducted with 10 participants who were selected using the purposive sampling method to participate in semi-structured interviews. Data were audio-recorded, transcribed verbatim and thematically analysed. Results: Two themes and 12 sub-themes were identified during the data analysis, namely individual and group influencing factors, as well as contextual influencing factors. Conclusion: This study revealed that the COVID-19 vaccination mandatory policy influenced the students' quality of life, academic performance and well-being. The findings from this study indicate that there were perceived barriers related to personal and contextual influencing factors than benefits of COVID-19 vaccination. Contribution: The understanding of and insight into the influences of the mandatory vaccination policy provided a basis for further strategies that may be developed to address COVID-19 vaccine infodemic, vaccine hesitancy and its risk effects. This can be done through collaboration with different stakeholders to educate health science students about the perceived benefits of COVID-19 vaccination.
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BACKGROUND: The increasing burden of cancer has economic implications for the healthcare system in England. However, there is limited evidence on the cost of cancer treatment. We calculated the costs of initial cancer treatment (resection, radiotherapy, systemic anti-cancer therapy [SACT]) based on stage at diagnosis. METHODS: Data from England's National Cancer Registration Dataset were matched to English Hospital, Radiotherapy and SACT data for breast, lung, prostate, colon and rectal cancers diagnosed between 2016 and 2018. Treatment data were matched to National Schedule of Reference Costs data to calculate the cost of each treatment event. RESULTS: Breast, colon and rectal cancers treated with resection, radiotherapy or SACT had increasing costs with later stage at diagnosis; costs for lung and prostate cancers were lower at stages 1 and 4 compared to stages 2 and 3. In general, surgery and SACT were the most expensive treatments. Radiotherapy and SACT costs showed little change across stages 1-3; radiotherapy costs decreased in stage 4, while SACT costs increased. CONCLUSIONS: This analysis estimates initial treatment costs by stage based on observed data. Future research can build on this to provide more comprehensive costings associated with cancer; this is important for future planning of cancer services.
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OBJECTIVE: Sport participation may have quality-of-life benefits for people with chronic breathlessness; however, its feasibility and impact on health are unknown. We aimed to synthesise the scientific literature concerning the impact of sport for people with chronic breathlessness. DATA SOURCES: Searches of MEDLINE, CINAHL, PsycINFO, Embase, SPORTDiscus and Google Scholar were conducted (May 2023). REVIEW METHODS: Studies were included if they assessed the impact of sport with participants who were likely to suffer from chronic breathlessness due to an underlying condition (e.g. severe asthma, heart failure). A convergent-segregated approach to synthesis in accordance with the JBI methodology for mixed-methods reviews was utilised, including meta-analytic and meta-aggregation analyses. RESULTS: A total of 22 studies met the inclusion criteria. Studies sampled 1017 participants from 13 different countries, with sample sizes ranging from 5 to 185. Causes of breathlessness consisted of chronic respiratory diseases (9 studies) and coronary heart disease (13 studies). Design-wise, 18 reported quantitative methods, 3 qualitative, and 1 mixed-methods. CONCLUSIONS: Sports were well-adhered to with only minor/unrelated adverse events reported. Improvements in exercise capacity were observed although there was no impact on health-related quality of life. Other quantitative outcomes extracted varied widely across studies, making it difficult to draw firm conclusions. Participation in sports was reliably recorded at intensity consistent with moderate-to-vigorous activity despite being self-paced. Qualitative themes emphasised the positive elements of sport participation, namely, social cohesion, the capacity to incorporate culture, and the idea that participation is enjoyable rather than a necessary chore to maintain one's health.
Subject(s)
Quality of Life , Respiration Disorders , Humans , Dyspnea/etiology , Exercise , Activities of Daily LivingABSTRACT
People with chronic obstructive pulmonary disease (COPD) have a higher prevalence of pain and a greater risk of falls than their healthy peers. As pain has been associated with an increased risk of falls in older adults, this study investigated the association between pain and falls in people with COPD compared to healthy controls. Data from the English Longitudinal Study of Ageing were used to establish an association between pain and falls when modelled with a generalised ordinal logistic regression and adjusted for sex, age, wealth, and education (complete case analysis only; n = 806 COPD, n = 3898 healthy controls). The odds were then converted to the predicted probabilities of falling. The predicted probability of falling for people with COPD was greater across all pain categories than for healthy controls; for COPD with (predicted probability % [95%CI]), no pain was 20% [17 to 25], with mild pain was 28% [18 to 38], with moderate pain was 28% [22 to 34] with severe pain was 39% [30 to 47] and for healthy controls with no pain was 17% [16 to 18], mild pain 22% [18 to 27], moderate pain 25% [20 to 29] and severe pain 27% [20 to 35]. The probability of falling increased across pain categories in individuals with COPD, with the most severe pain category at a nearly 40% probability of falling, indicating a potential interaction between COPD and pain.
Subject(s)
Accidental Falls , Pulmonary Disease, Chronic Obstructive , Aged , Humans , Aging , Longitudinal Studies , Pain/epidemiology , Pain/complications , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/epidemiology , Male , FemaleABSTRACT
Cortical spreading depolarization (CSD) is a key pathophysiological event that underlies visual and sensory auras in migraine. CSD is also thought to drive the headache phase in migraine by promoting the activation and mechanical sensitization of trigeminal primary afferent nociceptive neurons that innervate the cranial meninges. The factors underlying meningeal nociception in the wake of CSD remain poorly understood but potentially involve the parenchymal release of algesic mediators and damage-associated molecular patterns, particularly ATP. Here, we explored the role of ATP-P2X purinergic receptor signaling in mediating CSD-evoked meningeal afferent activation and mechanical sensitization. Male rats were subjected to a single CSD episode. In vivo, extracellular single-unit recording was used to measure meningeal afferent ongoing activity changes. Quantitative mechanical stimuli using a servomotor force-controlled stimulator assessed changes in the afferent's mechanosensitivity. Manipulation of meningeal P2X receptors was achieved via local administration of pharmacological agents. Broad-spectrum P2X receptor inhibition, selective blockade of the P2X7 receptor, and its related Pannexin 1 channel suppressed CSD-evoked afferent mechanical sensitization but did not affect the accompanying afferent activation response. Surprisingly, inhibition of the pronociceptive P2X2/3 receptor did not affect the activation or sensitization of meningeal afferents post-CSD. P2X7 signaling underlying afferent mechanosensitization was localized to the meninges and did not affect CSD susceptibility. We propose that meningeal P2X7 and Pannexin 1 signaling, potentially in meningeal macrophages or neutrophils, mediates the mechanical sensitization of meningeal afferents, which contributes to migraine pain by exacerbating the headache during normally innocuous physical activities.SIGNIFICANCE STATEMENT Activation and sensitization of meningeal afferents play a key role in migraine headache, but the underlying mechanisms remain unclear. Here, using a rat model of migraine with aura involving cortical spreading depolarization (CSD), we demonstrate that meningeal purinergic P2X7 signaling and its related Pannexin 1 pore, but not nociceptive P2X2/3 receptors, mediate prolonged meningeal afferent sensitization. Additionally, we show that meningeal P2X signaling does not contribute to the increased afferent ongoing activity in the wake of CSD. Our finding points to meningeal P2X7 signaling as a critical mechanism underlying meningeal nociception in migraine, the presence of distinct mechanisms underlying the activation and sensitization of meningeal afferents in migraine, and highlight the need to target both processes for effective migraine therapy.
Subject(s)
Migraine Disorders , Nociceptors , Rats , Male , Animals , Meninges , Headache , Adenosine Triphosphate/pharmacologyABSTRACT
Horseshoe bats are the natural hosts of the Sarbecovirus subgenus that includes SARS-CoV and SARS-CoV- 2. Despite the devastating impact of the COVID-19 pandemic, there is still little known about the underlying epidemiology and virology of sarbecoviruses in their natural hosts, leaving large gaps in our pandemic preparedness. Here we describe the results of PCR testing for sarbecoviruses in the two horseshoe bat species (Rhinolophus hipposideros and R. ferrumequinum) present in Great Britain, collected in 2021-22 during the peak of COVID-19 pandemic. One hundred and ninety seven R. hipposideros samples from 33 roost sites and 277 R. ferrumequinum samples from 20 roost sites were tested. No coronaviruses were detected in any samples from R. ferrumequinum whereas 44 and 56â% of individual and pooled (respectively) faecal samples from R. hipposideros across multiple roost sites tested positive in a sarbecovirus-specific qPCR. Full genome sequences were generated from three of the positive samples (and partial genomes from two more) using Illumina RNAseq on unenriched samples. Phylogenetic analyses showed that the obtained sequences belong to the same monophyletic clade, with >95â% similarity to previously-reported European isolates from R. hipposideros. The sequences differed in the presence or absence of accessory genes ORF 7b, 9b and 10. All lacked the furin cleavage site of SARS-CoV-2 spike gene and are therefore unlikely to be infective for humans. These results demonstrate a lack, or at least low incidence, of SARS-CoV-2 spill over from humans to susceptible GB bats, and confirm that sarbecovirus infection is widespread in R. hipposideros. Despite frequently sharing roost sites with R. ferrumequinum, no evidence of cross-species transmission was found.
Subject(s)
COVID-19 , Chiroptera , Severe acute respiratory syndrome-related coronavirus , Animals , Humans , Phylogeny , Pandemics , COVID-19/epidemiology , SARS-CoV-2/geneticsABSTRACT
People with respiratory disease have increased risk of developing frailty, which is associated with worse health outcomes. There is growing evidence of the role of rehabilitation in managing frailty in people with respiratory disease. However, several challenges remain regarding optimal methods of identifying frailty and delivering rehabilitation for this population. The aims of this American Thoracic Society workshop were to outline key definitions and concepts around rehabilitation for people with respiratory disease and frailty, synthesize available evidence, and explore how programs may be adapted to align to the needs and experiences of this population. Across two half-day virtual workshops, 20 professionals from diverse disciplines, professions, and countries discussed key developments and identified opportunities for future research, with additional input via online correspondence. Participants highlighted a "frailty rehabilitation paradox" whereby pulmonary rehabilitation can effectively reduce frailty, but programs are challenging for some individuals with frailty to complete. Frailty should not limit access to rehabilitation; instead, the identification of frailty should prompt comprehensive assessment and tailored support, including onward referral for additional specialist input. Exercise prescriptions that explicitly consider symptom burden and comorbidities, integration of additional geriatric or palliative care expertise, and/or preemptive planning for disruptions to participation may support engagement and outcomes. To identify and measure frailty in people with respiratory disease, tools should be selected on the basis of sensitivity, specificity, responsiveness, and feasibility for their intended purpose. Research is required to expand understanding beyond the physical dimensions of frailty and to explore the merits and limitations of telerehabilitation or home-based pulmonary rehabilitation for people with chronic respiratory disease and frailty.
Subject(s)
Frailty , Respiration Disorders , Respiratory Tract Diseases , Telerehabilitation , Humans , United States , Aged , Telerehabilitation/methods , Palliative CareABSTRACT
OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) is complicated by chronic pain. People with COPD report higher pain prevalence than the general population. Despite this, chronic pain management is not reflected in current COPD clinical guidelines and pharmacological treatments are often ineffective. We conducted a systematic review that aimed to establish the efficacy of existing non-pharmacological and non-invasive interventions on pain and identify behaviour change techniques (BCTs) associated with effective pain management. METHODS: A systematic review was conducted with reference to Preferred Reporting Items for Systematic Review (PRISMA) [1], Systematic review without Meta analysis (SWIM) standards [2] and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines [3]. We searched 14 electronic databases for controlled trials of non-pharmacological and non-invasive interventions where the outcome measure assessed pain or contained a pain subscale. RESULTS: Twenty-nine studies were identified involving 3,228 participants. Seven interventions reported a minimally important clinical difference in pain outcomes, although only two of these reached statistical significance (p < 0.05). A third study reported statistically significant outcomes, but this was not clinically significant (p = 0.0273). Issues with intervention reporting prevented identification of active intervention ingredients (i.e., BCTs). CONCLUSIONS: Pain appears to be a meaningful issue for many individuals with COPD. However, intervention heterogeneity and issues with methodological quality limit certainty about the effectiveness of currently available non-pharmacological interventions. An improvement in reporting is required to enable identification of active intervention ingredients associated with effective pain management.