Increase in invasive Streptococcus pyogenes M1 infections with close evolutionary genetic relationship, Iceland and Scotland, 2022 to 2023.

Group A Streptococcus isolates of the recently described M1UK clade have emerged to cause human infections in several European countries and elsewhere. Full-genome sequence analysis of M1 isolates discovered a close genomic relationship between some isolates from Scotland and the majority of isolates from Iceland causing serious infections in 2022 and 2023. Phylogenetic analysis strongly suggests that an isolate from or related to Scotland was the precursor to an M1UK variant responsible for almost all recent M1 infections in Iceland.

Once daily combined inhaled steroid and ultra long-acting bronchodilator prescribing in pediatric asthma: a dual Center retrospective cohort study.

OBJECTIVE: A high proportion of children and adolescents who have "difficult" or therapy-resistant asthma, are found to have poor adherence to maintenance therapies. Such individuals are thus difficult asthmatics (for reasons of poor adherence) rather than being young people with true difficult asthma. In our centers, once daily ICS/ULABA (Relvar™) is considered if there is an increase in reported interval symptoms, asthma attacks requiring hospital attendance or rescue oral prednisolone, or persistently low lung function despite reported regular use of a twice daily ICS/LABA preparation. In the majority of these young people, a clinical history of overt non-adherence or a clinical suspicion of covert non-adherence will be noted. METHODS: The aim of our retrospective cohort study was to assess the clinical effectiveness of Relvar™ in a selected adolescent asthma population. RESULTS: In a pre-selected group of adolescents with likely poor prior adherence to inhaled therapies, a change to Relvar™ (once daily combined ICS/ULABA) led to improvements in asthma control, as assessed by ED attendances and oral steroid burden. CONCLUSIONS: A prospective study to verify these findings and also explore the effects on quality of life, asthma control, and adherence is warranted.

The presumed central nervous system effects of rocuronium in a neonate and its reversal with sugammadex.

We describe a 2-day-old male infant who received rocuronium as part of general anesthesia for a tracheal esophageal fistula repair. Postoperatively, he had prolonged central and peripheral neuromuscular blockade despite cessation of the rocuronium infusion several hours previously. This case discusses the presumed central nervous system effects of rocuronium in a neonate and its effective reversal with sugammadex.

Paediatric sleep diagnostics in the 21st century: the era of "sleep-omics"?

Paediatric sleep diagnostics is performed using complex multichannel tests in specialised centres, limiting access and availability and resulting in delayed diagnosis and management. Such investigations are often challenging due to patient size (prematurity), tolerability, and compliance with "gold standard" equipment. Children with sensory/behavioural issues, at increased risk of sleep disordered breathing (SDB), often find standard diagnostic equipment difficult.SDB can have implications for a child both in terms of physical health and neurocognitive development. Potential sequelae of untreated SDB includes failure to thrive, cardiopulmonary disease, impaired learning and behavioural issues. Prompt and accurate diagnosis of SDB is important to facilitate early intervention and improve outcomes.The current gold-standard diagnostic test for SDB is polysomnography (PSG), which is expensive, requiring the interpretation of a highly specialised physiologist. PSG is not feasible in low-income countries or outwith specialist sleep centres. During the coronavirus disease 2019 pandemic, efforts were made to improve remote monitoring and diagnostics in paediatric sleep medicine, resulting in a paradigm shift in SDB technology with a focus on automated diagnosis harnessing artificial intelligence (AI). AI enables interrogation of large datasets, setting the scene for an era of "sleep-omics", characterising the endotypic and phenotypic bedrock of SDB by drawing on genetic, lifestyle and demographic information. The National Institute for Health and Care Excellence recently announced a programme for the development of automated home-testing devices for SDB. Scorer-independent scalable diagnostic approaches for paediatric SDB have potential to improve diagnostic accuracy, accessibility and patient tolerability; reduce health inequalities; and yield downstream economic and environmental benefits.

Preferences for virtual versus in-person mental and physical healthcare in Canada: a descriptive study from a cohort of youth and their parents enriched for severe mental illness.

BACKGROUND: Virtual care may improve access to healthcare and may be well suited to digitally connected youth, but experts caution that privacy and technology barriers could perpetuate access inequities. Success of virtual care will depend on its alignment with patient preferences. However, information on preferences for virtual and in-person healthcare is missing, especially for youth. We sought to quantify preferences for and barriers to virtual versus in-person mental and physical healthcare in youth and their parents, including in vulnerable segments of the population such as families with a parent with severe mental illness (SMI). METHODS: Participants were 219 youth and 326 parents from the Families Overcoming Risks and Building Opportunities for Wellbeing cohort from Canada, of which 61% of youth had at least one parent with SMI. Participants were interviewed about healthcare preferences and access to privacy/technology between October 2021 and December 2022. RESULTS: Overall, youth reported a preference for in-person mental (66.6%) and physical healthcare (74.7%) versus virtual care or no preference, and to a somewhat lesser degree, so did their parents (48.0% and 53.9%). Half of participants reported privacy/technology barriers to virtual care, with privacy being the most common barrier. Preferences and barriers varied as a function of parent SMI status, socioeconomic status and rural residence. CONCLUSIONS: The majority of youth and parents in this study prefer in-person healthcare, and the preference is stronger in youth and in vulnerable segments of the population. Lack of privacy may be a greater barrier to virtual care than access to technology.

Role of overnight oximetry in assessing the severity of obstructive sleep apnoea in typically developing children: a multicentre study.

BACKGROUND AND OBJECTIVE: Cardiorespiratory polygraphy (CRP) is the predominant technology used to diagnose obstructive sleep apnoea (OSA) in tertiary centres in the UK. Nocturnal pulse oximetry (NPO) is, however, cheaper and more accessible. This study evaluated the ability of NPO indices to predict OSA in typically developing (TD) children. METHODS: Indices from simultaneous NPO and CRP recordings were compared in TD children (aged 1-16 years) referred to evaluate OSA in three tertiary centres. OSA was defined as an obstructive apnoea-hypopnoea index (OAHI) ≥1 event/hour. Receiver operating characteristic curves assessed the diagnostic accuracy of NPO indices including ODI3 (3% Oxygen Desaturation Index, ODI4 (4% Oxygen Desaturation Index), delta 12 s index and minimum oxygen saturation. Two-by-two tables were generated to determine the sensitivities and specificities of whole number cut-off values for predicting OAHIs ≥1, 5 and 10 events/hour. RESULTS: Recordings from 322 TD children, 197 male (61.2%), median age 4.9 years (range 1.1-15.6), were reviewed. OAHI was ≥1/hour in 144 (44.7%), ≥5/hour in 61 (18.9%) and ≥10/hour in 28 (8.7%) cases. ODI3 and ODI4 had the best diagnostic accuracy. ODI3 ≥7/hour and ODI4 ≥4/hour predicted OSA in TD children with sensitivities/specificities of 57.6%/85.4% and 46.2%/91.6%, respectively. ODI3 ≥8/hour was the best predictor of OAHI ≥5/hour (sensitivity 82.0%, specificity 84.3%). CONCLUSION: Raised ODI3 and ODI4 predict OSA in TD children with high specificity but variable sensitivity. NPO may be an alternative to diagnose moderate-severe OSA if access to CRP is limited. Low sensitivities to detect mild OSA mean that confirmatory CRP is needed if NPO is normal.

Standards for the care of people with cystic fibrosis; establishing and maintaining health.

This is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy.

Repeated Measurement of Microglia-Dendritic Spine Interactions Using Multi-Photon Imaging.

In recent decades, mounting evidence has shown that microglia play a vital role in maintaining synapses throughout life. This maintenance is done via numerous microglial processes, which are long, thin, and highly motile protrusions from the cell body that monitor their environment. However, due to the brevity of the contacts and the potentially transient nature of synaptic structures, establishing the underlying dynamics of this relationship has proven difficult. This article describes a method of using rapidly acquired multiphoton microscopy images to track microglial dynamics and microglia:synapse interactions and the fate of the synaptic structures following those interactions. First, we detail a method for capturing multiphoton images at 1-min intervals for approximately 1 hr and how that process can be done at multiple time points. We then discuss how best to prevent and account for any drifting of the region of interest that can occur during the imaging session and how to remove excessive background noise from those images. Finally, we detail the annotation process for dendritic spines and microglial processes using plugins in MATLAB and Fiji, respectively. These semi-automated plugins allow tracking of individual cell structures, even if both microglia and neurons are imaged in the same fluorescent channel. This protocol presents a method of tracking both microglial dynamics and synaptic structures, in the same animal, at multiple time points, giving the user information on process speed, branching, tip size, location, and dwell time, as well as any dendritic spine gains, losses, and size changes. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Rapid multiphoton image capture Basic Protocol 2: Image preparation using MATLAB and Fiji Basic Protocol 3: Dendritic spine and microglial processes annotation using ScanImage and TrackMate.

Phage therapy: Awareness and demand among clinicians in the United Kingdom.

Bacterial resistance or tolerance to antibiotics is costly to patients and healthcare providers. With the impact of antibiotic resistance forecast to grow, alternative antimicrobial approaches are needed to help treat patients with antibiotic refractory infections and reduce reliance upon existing antibiotics. There is renewed interest in bacteriophage (phage) therapy as a promising antimicrobial strategy. We therefore performed the first multi-specialty survey about phage therapy and the first such survey among clinicians in the United Kingdom. An anonymous 10-question survey of clinicians from medical and surgical specialties in two Scottish Health Boards was performed. The 90 respondents spanned 26 specialties and were predominantly consultants (73.3%). The respondents were concerned about antibiotic resistance in their clinical practice; 83 respondents estimated having seen 711 patients in the last 12 months whose infections were refractory to antibiotics (delaying or preventing resolution). Over half (58.8%) of the respondents had previously heard of phage therapy. Staphylococci, Pseudomonas and E. coli were identified as the highest cross-specialty priorities for the development of phage therapy. Together, 77 respondents estimated seeing 300 patients in the last 12 months for whom phage therapy may have been appropriate (an average of 3.9 patients per clinician). Most respondents (71.1%, n = 90) were already willing to consider using phage therapy in appropriate cases. Additional comments from the respondents affirmed the potential utility of phage therapy and highlighted a need for more information. The results of this survey demonstrate substantial demand for and willingness to use phage therapy in appropriate cases, both from individual clinicians and across specialties. Demand from a wide range of specialties illustrates the broad clinical utility of phage therapy and potential scope of impact. Widening access to phage therapy could deliver substantial clinical and financial benefits for patients and health authorities alike.

Manifestation of depression in speech overlaps with characteristics used to represent and recognize speaker identity.

The sound of a person's voice is commonly used to identify the speaker. The sound of speech is also starting to be used to detect medical conditions, such as depression. It is not known whether the manifestations of depression in speech overlap with those used to identify the speaker. In this paper, we test the hypothesis that the representations of personal identity in speech, known as speaker embeddings, improve the detection of depression and estimation of depressive symptoms severity. We further examine whether changes in depression severity interfere with the recognition of speaker's identity. We extract speaker embeddings from models pre-trained on a large sample of speakers from the general population without information on depression diagnosis. We test these speaker embeddings for severity estimation in independent datasets consisting of clinical interviews (DAIC-WOZ), spontaneous speech (VocalMind), and longitudinal data (VocalMind). We also use the severity estimates to predict presence of depression. Speaker embeddings, combined with established acoustic features (OpenSMILE), predicted severity with root mean square error (RMSE) values of 6.01 and 6.28 in DAIC-WOZ and VocalMind datasets, respectively, lower than acoustic features alone or speaker embeddings alone. When used to detect depression, speaker embeddings showed higher balanced accuracy (BAc) and surpassed previous state-of-the-art performance in depression detection from speech, with BAc values of 66% and 64% in DAIC-WOZ and VocalMind datasets, respectively. Results from a subset of participants with repeated speech samples show that the speaker identification is affected by changes in depression severity. These results suggest that depression overlaps with personal identity in the acoustic space. While speaker embeddings improve depression detection and severity estimation, deterioration or improvement in mood may interfere with speaker verification.

Managing Patient and Clinician Expectations of Phage Therapy in the United Kingdom.

Bacteriophage (phage) therapy is a promising alternative antimicrobial approach which has the potential to transform the way we treat bacterial infections. Phage therapy is currently being used on a compassionate basis in multiple countries. Therefore, if a patient has an antibiotic refractory infection, they may expect their clinician to consider and access phage therapy with the hope of improvement. The expectations of clinicians may be similar and may also include expectations around data collection. However, there are multiple biological and practical barriers to fulfilling patient and clinician expectations. While it is possible to access phage therapy, the path to acquisition is not straightforward and expectations therefore need to be managed appropriately to avoid raising false hope and undermining confidence in phage therapy. Phage scientists have an important contribution to make in educating clinicians and the broader public about phage therapy. However, it is clinicians that are responsible for managing the expectations of their patients and this relies on clear communication about the barriers and limitations.

Treating nontuberculous mycobacteria in children with cystic fibrosis: a multicentre retrospective study.

BACKGROUND: Respiratory infection with nontuberculous mycobacteria (NTM) in children with cystic fibrosis (CF) has increased in prevalence. The condition is difficult to diagnose and treatments are complex with limited evidence to guide practice. This study describes the approaches to diagnosis, management and consequences of treatment in a multicentre cohort of children with CF in the UK. METHODS: Retrospective data were collected from 11 CF specialist centres from patients less than 17 years old, treated for NTM infection between 2006 and 2017. Descriptive statistics were used to describe the clinical characteristics of children treated. Treatment regimens, adverse events and success of treatment, with respect to lung function and culture conversion, were evaluated. RESULTS: Data from 70 patients treated for NTM pulmonary disease were collated (60 Mycobacterium abscessus complex (MABSC); 10 M. avium complex (MAC)). Older age and previous diagnosis of allergic bronchopulmonary aspergillosis were all significantly associated with NTM. There was a wide variance in drug choice and side effects were reported with all agents. NTM eradication occurred in 80% of patients with MAC and 48% with MABSC, with variable outcomes on lung function. CONCLUSIONS: Diagnosis and treatment of NTM infection in children with CF is challenging. Treatment success is not guaranteed, particularly for MABSC. Large clinical trials are urgently required to evaluate treatment regimes and their suitability and efficacy in children.

Feasibility and efficacy of active remote monitoring of home ventilation in pediatrics.

BACKGROUND: Non-invasive positive airway pressure (PAP) therapy is used to treat children with sleep-disordered breathing. Effective management requires good adherence. In response to the problem of reduced adherence over time, a pilot study using ventilators equipped with technology to remotely monitor home adherence was undertaken. METHODS: From July 2019, children requiring PAP therapy consented for remote monitoring. Data collected included ventilator usage, apnea-hypopnea index (AHI), and mask leak. Parents were contacted on Days 14, 42, and 90 post-establishment. A proforma was used to assess parental understanding and ways to improve therapy adherence. A parental feedback questionnaire was completed on Day 90 of the study. RESULTS: Median nightly PAP usage over 90-day post-establishment was 6.58 h (interquartile range: 2.47-8.62); 60% of patients met criteria for good adherence (>4 h for >70% of nights). There was a decrease in median nightly usage in Week 1 (6.92 h) versus Week 12 (6.15 h), p = 0.04. Mask leak was higher in Week 1 (17.7 L/min) versus Week 12 (14.7 L/min), p = 0.053. There was no significant difference in AHI between Week 1 (2.7/h) versus Week 12 (2.3/h), p = 0.75. 45% of questionnaire respondents felt active remote monitoring positively influenced PAP usage, whilst 84% reported overall satisfaction with PAP therapy. CONCLUSIONS: Remote monitoring technology has the potential to guide adjustments in PAP therapy, monitor and improve adherence in children, and reduce the burden of hospital-based review. Preliminary work shows high approval from parents.

Subthreshold repetitive transcranial magnetic stimulation drives structural synaptic plasticity in the young and aged motor cortex.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool commonly used to drive neural plasticity in the young adult and aged brain. Recent data from mouse models have shown that even at subthreshold intensities (0.12 T), rTMS can drive neuronal and glial plasticity in the motor cortex. However, the physiological mechanisms underlying subthreshold rTMS induced plasticity and whether these are altered with normal ageing are unclear. OBJECTIVE: To assess the effect of subthreshold rTMS, using the intermittent theta burst stimulation (iTBS) protocol on structural synaptic plasticity in the mouse motor cortex of young and aged mice. METHODS: Longitudinal in vivo 2-photon microscopy was used to measure changes to the structural plasticity of pyramidal neuron dendritic spines in the motor cortex following a single train of subthreshold rTMS (in young adult and aged animals) or the same rTMS train administered on 4 consecutive days (in young adult animals only). Data were analysed with Bayesian hierarchical generalized linear regression models and interpreted with the aid of Bayes Factors (BF). RESULTS: We found strong evidence (BF > 10) that subthreshold rTMS altered the rate of dendritic spine losses and gains, dependent on the number of stimulation sessions and that a single session of subthreshold rTMS was effective in driving structural synaptic plasticity in both young adult and aged mice. CONCLUSION: These findings provide further evidence that rTMS drives synaptic plasticity in the brain and uncovers structural synaptic plasticity as a key mechanism of subthreshold rTMS induced plasticity.