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Background: In an era of increasing antimicrobial resistance, appropriate antimicrobials are essential to optimise patient outcomes. In 2017, antimicrobial use prevalence (AMU) on the two neurosurgical wards in our tertiary teaching hospital varied from 23% on ward A to 33% on ward B with 67% and 100% ‘appropriate’ prescriptions, respectively. In July 2018, a weekly antimicrobial stewardship multidisciplinary round led by a senior neurosurgery registrar commenced, attended by the antimicrobial stewardship team (AST). Research question: This report evaluates whether a multi-disciplinary approach on neurosurgical prescribing was beneficial, specifically in reducing AMU. Materials and methods: The following data was collected on AST rounds for 30 weeks in total from August 2018 to July 2019: number of patients on antimicrobials, appropriateness and stewardship actions. A questionnaire was distributed to neurosurgical doctors on two occasions to canvass opinions and attitudes on antimicrobial prescribing. Results: 1716 prescriptions were reviewed (mean 57.2 per week). Of these 321 (18.7%) included antimicrobial prescriptions; 200 on ward A (19.8%), and 121 on ward B (17%), representing a decrease in AMU from 2017. The majority of antimicrobial prescriptions, 271 (84.4%) were deemed appropriate. Stewardship actions were taken in 215 (67%) prescriptions.Fifteen questionnaires were completed by neurosurgical doctors. The majority, 87%, stated the AST round was helpful overall. 93% indicated that informal training on the AST round was a source of education in antibiotic prescribing. Discussion and conclusion: The weekly AST round provided a timely opportunity for multidisciplinary discussion, implementation of antimicrobial stewardship actions and opportunistic antimicrobial stewardship education.

Abstract Virulence and metabolism are often interlinked to control the expression of essential colonisation factors in response to host-associated signals. Here, we identified an uncharacterised transporter of the dietary monosaccharide ʟ-arabinose that is widely encoded by the zoonotic pathogen enterohaemorrhagic Escherichia coli (EHEC), required for full competitive fitness in the mouse gut and highly expressed during human infection. Discovery of this transporter suggested that EHEC strains have an enhanced ability to scavenge ʟ-arabinose and therefore prompted us to investigate the impact of this nutrient on pathogenesis. Accordingly, we discovered that ʟ-arabinose enhances expression of the EHEC type 3 secretion system, increasing its ability to colonise host cells, and that the underlying mechanism is dependent on products of its catabolism rather than the sensing of ʟ-arabinose as a signal. Furthermore, using the murine pathogen Citrobacter rodentium, we show that ʟ-arabinose metabolism provides a fitness benefit during infection via virulence factor regulation, as opposed to supporting pathogen growth. Finally, we show that this mechanism is not restricted to ʟ-arabinose and extends to other pentose sugars with a similar metabolic fate. This work highlights the importance integrating central metabolism with virulence regulation in order to maximise competitive fitness of enteric pathogens within the host-niche.

Abstract Sustainably managing fisheries requires regular and reliable evaluation of stock status. However, most multispecies reef fisheries around the globe tend to lack research and monitoring capacity, preventing the estimation of sustainable reference points against which stocks can be assessed. Here, combining fish biomass data for >2000 coral reefs, we estimate site-specific sustainable reference points for coral reef fisheries and use these and available catch estimates to assess the status of global coral reef fish stocks. We reveal that >50% of sites and jurisdictions with available information have stocks of conservation concern, having failed at least one fisheries sustainability benchmark. We quantify the trade-offs between biodiversity, fish length, and ecosystem functions relative to key benchmarks and highlight the ecological benefits of increasing sustainability. Our approach yields multispecies sustainable reference points for coral reef fisheries using environmental conditions, a promising means for enhancing the sustainability of the world’s coral reef fisheries.

Topological insulator (TI) nanoribbons with proximity-induced superconductivity are a promising platform for Majorana bound states (MBSs). In this work, we consider a detailed modeling approach for a TI nanoribbon in contact with a superconductor via its top surface, which induces a superconducting gap in its surface-state spectrum. The system displays a rich phase diagram with different numbers of end-localized MBSs as a function of chemical potential and magnetic flux piercing the cross section of the ribbon. These MBSs can be robust or fragile upon consideration of electrostatic disorder. We simulate a tunneling spectroscopy setup to probe the different topological phases of top-proximitized TI nanoribbons. Our simulation results indicate that a top-proximitized TI nanoribbon is ideally suited for realizing fully gapped topological superconductivity, in particular when the Fermi level is pinned near the Dirac point. In this regime, the setup yields a single pair of MBSs, well separated at opposite ends of the proximitized ribbon, which gives rise to a robust quantized zero-bias conductance peak.

We use a superconducting microresonator as a cavity to sense absorption of microwaves by a superconducting quantum point contact defined by surface gates over a proximitized two-dimensional electron gas. Renormalization of the cavity frequency with phase difference across the point contact is consistent with coupling to Andreev bound states. Near π phase difference, we observe random fluctuations in absorption with gate voltage, related to quantum interference-induced modulations in the electron transmission. Close to pinch-off, we identify features consistent with the presence of a single Andreev bound state and describe the Andreev-cavity interaction using a Jaynes-Cummings model. By fitting the weak Andreev-cavity coupling, we extract ∼GHz decoherence consistent with charge noise and the transmission dispersion associated with a localized state.

Competitive bacteria-bacteriophage interactions have resulted in the evolution of a plethora of bacterial defense systems preventing phage propagation. In recent years, computational and bioinformatic approaches have underpinned the discovery of numerous novel bacterial defense systems. Anti-phage systems are frequently encoded together in genomic loci termed defense islands. Here we report the identification and characterisation of a novel anti-phage system, that we have termed Shield, which forms part of the Pseudomonas defensive arsenal. The Shield system comprises the core component ShdA, a membrane-bound protein harboring an RmuC domain. Heterologous production of ShdA alone is sufficient to mediate bacterial immunity against several phages. We demonstrate that Shield and ShdA confer population-level immunity and that they can also decrease transformation efficiency. We further show that ShdA homologues can degrade DNA in vitro and, when expressed in a heterologous host, can alter the organisation of the host chromosomal DNA. Use of comparative genomic approaches identified how Shield can be divided into four subtypes, three of which contain additional components that in some cases can negatively affect the activity of ShdA and/or provide additional lines of phage defense. Collectively, our results identify a new player within the Pseudomonas bacterial immunity arsenal that displays a novel mechanism of protection, and reveals a role for RmuC domains in phage defense.

Background: Self-management support (SMS) is a recommended component of cancer survivorship care that improves health-related quality of life and reduces healthcare utilisation. However, widespread implementation has been difficult to achieve, with a gap in the literature on system-wide implementation efforts. This study examines contextual factors perceived to influence SMS adoption and sustainment in cancer centres in the Republic of Ireland., Method: Semistructured interviews were conducted with 47 key informants from 20 cancer organisations across community and hospital settings. Participants were asked to report the level of adoption and sustainment of SMS at their organisation. This information was used to categorise organisations as low, medium or high implementers. We conducted cross-case analysis following the principles of Framework Analysis. Using the Consolidated Framework for Implementation Research as a menu of constructs, we examined factors influencing adoption and sustainment and variation in levels of implementation., Results: National policy, external accreditation, external financing opportunities and the presence of champions in organisations are influential early in the implementation process driving adoption. Healthcare provider-led programmes and evidence of SMS improving patient outcomes and aligning with an organisation's priorities are necessary to secure buy-in, particularly among senior leadership. An organisational culture of entrepreneurship enables adoption and sustainment, with resources and a culture supporting staff well-being enabling sustainment., Conclusion: While national policy is a driver, additional factors related to programme attributes and local contextual features such as the presence of champions, organisational readiness and culture influence implementation. The results may be used for future evaluations of SMS implementation in cancer survivorship care and to inform the development of tailored implementation strategies., Competing Interests: Competing interests: RC has received salary support from Breakthrough Cancer Research via her institution. RC has received an unrestricted educational grant from Pfizer, and research funding for clinical trials from MSD Ireland, Pfizer, Daichii Sankyo and AstraZeneca; all to her institution. RC has consulted for AstraZeneca/Daichii, Gilead and Seagen. She has received travel/conference support from Novartis, Roche and Gilead. JH has received institutional research grant funding from Pfizer Ireland in the past., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Self-harm is a major health issue resulting in high societal costs. Few psychological and psychosocial interventions have shown effectiveness in reducing repeat self-harm., Objective: To assess the cost-effectiveness of psychological and psychosocial interventions that have shown evidence of effectiveness in adults and CYP (children and young people) who have self-harmed., Methods: Using effectiveness data from Cochrane reviews, we developed two decision-analytical models to compare costs and quality-adjusted life years (QALYs) of cognitive behavioural therapy (CBT)-informed psychological therapy added to treatment as usual (TAU) versus TAU alone for adults who have self-harmed, and of dialectical behavioural therapy for adolescents (DBT-A) versus enhanced TAU for CYP who have self-harmed, respectively, from a National Health Service and personal social services perspective in England. Other model input parameters were obtained from published sources, supplemented by expert opinion., Findings: The incremental cost-effectiveness ratio (ICER) of CBT-informed psychological therapy added to TAU versus TAU alone for adults who have self-harmed was £9088/QALY. The ICER of DBT-A versus enhanced TAU for CYP who have self-harmed was £268 601/QALY. Results were overall robust to the alternative scenarios tested., Conclusions and Clinical Implications: CBT-informed psychological therapy appears to be cost-effective for adults who have self-harmed, which contributes to evidence for its implementation in services. Currently, DBT-A does not seem to be cost-effective for CYP who have self-harmed. The economic analyses were informed by clinical evidence of moderate-to-low (CBT) and low (DBT-A) quality. Further clinical and economic evidence for DBT-A and other psychological and psychosocial interventions for people who have self-harmed is required., Competing Interests: Competing interests: IM, FP, RC and SP received support from the National Institute for Health and Care Excellence (NICE) for the submitted work. AW, AC, FM, KL and NK declared the following interests based on NICE’s policy on conflicts of interests:https://www.nice.org.uk/guidance/ng225/documents/register-of-interests. KH is a member of the National Suicide Prevention Strategy for England Advisory Group. The authors report no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

Background: Racially minoritized populations experience higher rates of adverse birth outcomes than White populations in the U.S. We estimated the mediating effect of neighborhood social and physical environments on disparities in adverse birth outcomes in California., Method: We used birthing parent's residential address for California live birth records from 2019 to estimate census block group Area Deprivation Index and census tract level measures of ambient fine particulate matter (PM2.5), drinking water contamination, tree canopy coverage, as a measure of greenspace, potential heat vulnerability, and noise. We performed mediation analysis to assess whether neighborhood factors explain racial/ethnic disparities in preterm birth (PTB) and term-birth low birth weight (TLBW) comparing Black, Latinx, and Asian with White births after controlling for individual-level factors., Results: Black, Latinx, and Asian parents had PTB rates that were 67%, 36%, and 11% higher, and TLBW rates that were 150%, 38%, and 81% higher than Whites. Neighborhood deprivation contributed 7% (95% CI: 3%, 11%) to the Black-White and 9% (95% CI: 6%, 12%) to the Latinx-White disparity in PTB, and 8% (95% CI: 3%, 12%) of the Black-White and 9% (95% CI: 5%, 15%) of the Latinx-White disparity in TLBW. Drinking water contamination contributed 2% (95% CI: 1%, 4%) to the Latinx-White disparity in PTB. Lack of greenspace accounted for 7% (95% CI: 2%, 10%) of the Latinx-White PTB disparity and 7% (95% CI: 3%, 12%) of the Asian-White PTB disparity. PM2.5 contributed 11% (95% CI: 5%, 18%), drinking water contamination contributed 3% (95% CI: 1%, 7%), and potential heat vulnerability contributed 2% (95% CI: 1%, 3%) to the Latinx-White TLBW disparity. Lack of green space contributed 3% (95% CI: 1%, 6%) to the Asian-White TLBW disparity., Conclusions: Our study suggests social environments explain portions of Black/Latinx-White disparities while physical environments explain Latinx/Asian-White disparities in PTB and TLBW., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

California faces several serious direct and indirect climate exposures that can adversely affect public health, some of which are already occurring. The public health burden now and in the future will depend on atmospheric greenhouse gas concentrations, underlying population vulnerabilities, and adaptation efforts. Here, we present a structured review of recent literature to examine the leading climate risks to public health in California, including extreme heat, extreme precipitation, wildfires, air pollution, and infectious diseases. Comparisons among different climate-health pathways are difficult due to inconsistencies in study design regarding spatial and temporal scales and health outcomes examined. We find, however, that the current public health burden likely affects thousands of Californians each year, depending on the exposure pathway and health outcome. Further, while more evidence exists for direct and indirect proximal health effects that are the focus of this review, distal pathways (e.g., impacts of drought on nutrition) are more uncertain but could add to this burden. We find that climate adaptation measures can provide significant health benefits, particularly in disadvantaged communities. We conclude with priority recommendations for future analyses and solution-driven policy actions., Competing Interests: Competing interests statement:The authors declare no competing interest.

In California, wildfire risk and severity have grown substantially in the last several decades. Research has characterized extensive adverse health impacts from exposure to wildfire-attributable fine particulate matter (PM 2.5 ), but few studies have quantified long-term outcomes, and none have used a wildfire-specific chronic dose-response mortality coefficient. Here, we quantified the mortality burden for PM 2.5 exposure from California fires from 2008 to 2018 using Community Multiscale Air Quality modeling system wildland fire PM 2.5 estimates. We used a concentration-response function for PM 2.5 , applying ZIP code-level mortality data and an estimated wildfire-specific dose-response coefficient accounting for the likely toxicity of wildfire smoke. We estimate a total of 52,480 to 55,710 premature deaths are attributable to wildland fire PM 2.5 over the 11-year period with respect to two exposure scenarios, equating to an economic impact of $432 to $456 billion. These findings extend evidence on climate-related health impacts, suggesting that wildfires account for a greater mortality and economic burden than indicated by earlier studies.

An out-of-season increase in cases of invasive Group A streptococcus (iGAS) was observed in Ireland between October 2022 and August 2023. We describe the management of an iGAS outbreak involving three nursing home residents in Ireland in early 2023. A regional Department of Public Health was notified of an iGAS case in a nursing home resident in January 2023. When two further cases among residents were notified 7 days later, an outbreak was declared. Surveillance for GAS/iGAS infection in residents and staff was undertaken. The site was visited to provide infection prevention and control (IPC) support. Isolates were emm typed. A total of 38 residents and 29 staff in contact with resident cases were provided with antibiotic chemoprophylaxis. Seven additional staff with no direct resident contact also received chemoprophylaxis after finding one probable localised GAS infection among them. No more iGAS cases subsequently occurred.Site visit recommendations included advice on terminal cleaning and cleaning of shared equipment, as well as strengthening staff education on hand hygiene and masking. All isolates were of emm subtype 18.12, a subtype not previously detected in Ireland. Key outbreak control measures were rapid delivery of IPC support and chemoprophylaxis. Emm 18 is infrequently associated with GAS infections.

Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood-brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog., (© 2024. The Author(s).)

An important consideration for biopharmaceutical processes is the cost of goods (CoGs) of biotherapeutics manufacturing. CoGs can be reduced by dramatically increasing the productivity of the bioreactor process. In this study, we demonstrate that an intensified process which couples a perfused N-1 seed reactor and a fully automated high inoculation density (HID) N stage reactor substantially increases the bioreactor productivity as compared to a low inoculation density (LID) control fed-batch process. A panel of six CHOK1SV GS-KO® CHO cell lines expressing three different monoclonal antibodies was evaluated in this intensified process, achieving an average 85% titer increase and 132% space-time yield (STY) increase was demonstrated when comparing the 12-day HID process to a 15-day LID control process. These productivity increases were enabled by automated nutrient feeding in both the N-1 and N stage bioreactors using in-line process analytical technologies (PAT) and feedback control. The N-1 bioreactor utilized in-line capacitance to automatically feed the bioreactor based on a capacitance-specific perfusion rate (CapSPR). The N-stage bioreactor utilized in-line Raman spectroscopy to estimate real-time concentrations of glucose, phenylalanine, and methionine, which are held to target set points using automatic feed additions. These automated feeding methodologies were shown to be generalizable across six cell lines with diverse feed requirements. We show this new process can accommodate clonal diversity and reproducibly achieve substantial titer uplifts compared to traditional cell culture processes, thereby establishing a baseline technology platform upon which further increases bioreactor productivity and CoGs reduction can be achieved., (© 2023 Lonza. Biotechnology Progress published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Background: Most government efforts to control the COVID-19 pandemic revolved around non-pharmaceutical interventions (NPIs) and vaccination. However, many respiratory diseases show distinctive seasonal trends. In this manuscript, we examined the contribution of these three factors to the progression of the COVID-19 pandemic., Methods: Pearson correlation coefficients and time-lagged analysis were used to examine the relationship between NPIs, vaccinations and seasonality (using the average incidence of endemic human beta-coronaviruses in Sweden over a 10-year period as a proxy) and the progression of the COVID-19 pandemic as tracked by deaths; cases; hospitalisations; intensive care unit occupancy and testing positivity rates in six Northern European countries (population 99.12 million) using a population-based, observational, ecological study method., Findings: The waves of the pandemic correlated well with the seasonality of human beta-coronaviruses (HCoV-OC43 and HCoV-HKU1). In contrast, we could not find clear or consistent evidence that the stringency of NPIs or vaccination reduced the progression of the pandemic. However, these results are correlations and not causations., Implications: We hypothesise that the apparent influence of NPIs and vaccines might instead be an effect of coronavirus seasonality. We suggest that policymakers consider these results when assessing policy options for future pandemics., Limitations: The study is limited to six temperate Northern European countries with spatial and temporal variations in metrics used to track the progression of the COVID-19 pandemic. Caution should be exercised when extrapolating these findings.

Background: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. Although most episodes of OME in children resolve spontaneously within a few months, when persistent it may lead to behavioural problems and a delay in expressive language skills. Management of OME includes watchful waiting, medical, surgical and other treatments, such as autoinflation. Oral or topical steroids are sometimes used to reduce inflammation in the middle ear., Objectives: To assess the effects (benefits and harms) of topical and oral steroids for OME in children., Search Methods: We searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished studies on 20 January 2023., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared topical or oral steroids with either placebo or watchful waiting (no treatment)., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes, determined by a multi-stakeholder prioritisation exercise, were: 1) hearing, 2) OME-specific quality of life and 3) systemic corticosteroid side effects. Secondary outcomes were: 1) presence/persistence of OME, 2) other adverse effects (including local nasal effects), 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial outcomes, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function and 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds., Main Results: We included 26 studies in this review (2770 children). Most studies of oral steroids used prednisolone for 7 to 14 days. Studies of topical (nasal) steroids used various preparations (beclomethasone, fluticasone and mometasone) for between two weeks and three months. All studies had at least some concerns regarding risk of bias. Here we report our primary outcomes and main secondary outcome, at the longest reported follow-up. Oral steroids compared to placebo Oral steroids probably result in little or no difference in the proportion of children with normal hearing after 12 months (69.7% of children with steroids, compared to 61.1% of children receiving placebo, risk ratio (RR) 1.14, 95% confidence interval (CI) 0.97 to 1.33; 1 study, 332 participants; moderate-certainty evidence). There is probably little or no difference in OME-related quality of life (mean difference (MD) in OM8-30 score 0.07, 95% CI -0.2 to 0.34; 1 study, 304 participants; moderate-certainty evidence). Oral steroids may reduce the number of children with persistent OME at 6 to 12 months, but the size of the effect was uncertain (absolute risk reduction ranging from 13.3% to 45%, number needed to treat (NNT) of between 3 and 8; low-certainty evidence). The evidence was very uncertain regarding the risk of systemic corticosteroid side effects, and we were unable to conduct any meta-analysis for this outcome. Oral steroids compared to no treatment Oral steroids may result in little or no difference in the persistence of OME after three to nine months (74.5% children receiving steroids versus 73% of those receiving placebo; RR 1.02, 95% CI 0.89 to 1.17; 2 studies, 258 participants; low-certainty evidence). The evidence on adverse effects was very uncertain. We did not identify any evidence on hearing or disease-related quality of life. Topical (intranasal) steroids compared to placebo We did not identify data on the proportion of children who returned to normal hearing. However, the mean change in hearing threshold after two months was -0.3 dB lower (95% CI -6.05 to 5.45; 1 study, 78 participants; very low-certainty evidence). The evidence suggests that nasal steroids make little or no difference to disease-specific quality of life after nine months (OM8-30 score, MD 0.05 higher, 95% CI -0.36 to 0.46; 1 study, 82 participants; low-certainty evidence). The evidence is very uncertain regarding the effect of nasal steroids on persistence of OME at up to one year. Two studies reported this: one showed a potential benefit for nasal steroids, the other showed a benefit with placebo (2 studies, 206 participants). The evidence was also very uncertain regarding the risk of corticosteroid-related side effects, as we were unable to provide a pooled effect estimate. Topical (intranasal) steroids compared to no treatment We did not identify data on the proportion of children who returned to normal hearing. However, the mean difference in final hearing threshold after four weeks was 1.95 dB lower (95% CI -3.85 to -0.05; 1 study, 168 participants; low-certainty evidence). Nasal steroids may reduce the persistence of OME after eight weeks, but the evidence was very uncertain (58.5% of children receiving steroids, compared to 81.3% of children without treatment, RR 0.72, 95% CI 0.57 to 0.91; 2 studies, 134 participants). We did not identify any evidence on disease-related quality of life or adverse effects., Authors' Conclusions: Overall, oral steroids may have little effect in the treatment of OME, with little improvement in the number of children with normal hearing and no effect on quality of life. There may be a reduction in the proportion of children with persistent disease after 12 months. However, this benefit may be small and must be weighed against the potential for adverse effects associated with oral steroid use. The evidence for nasal steroids was all low- or very low-certainty. It is therefore less clear if nasal steroids have any impact on hearing, quality of life or persistence of OME. Evidence on adverse effects was very limited. OME is likely to resolve spontaneously for most children. The potential benefit of treatment may therefore be small and should be balanced with the risk of adverse effects. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. It may cause hearing loss which, when persistent, may lead to developmental delay, social difficulty and poor quality of life. Management includes watchful waiting, autoinflation, medical and surgical treatment. Insertion of ventilation tubes has often been used as the preferred treatment., Objectives: To evaluate the effects (benefits and harms) of ventilation tubes (grommets) for OME in children., Search Methods: We searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished trials on 20 January 2023., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs in children (6 months to 12 years) with OME for ≥ 3 months. We included studies that compared ventilation tube (VT) insertion with five comparators: no treatment, watchful waiting (ventilation tubes inserted later, if required), myringotomy, hearing aids and other non-surgical treatments., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were determined following a multi-stakeholder prioritisation exercise and were: 1) hearing; 2) OME-specific quality of life; 3) persistent tympanic membrane perforation (as a severe adverse effect of the surgery). Secondary outcomes were: 1) persistence of OME; 2) other adverse effects (including tympanosclerosis, VT blockage and pain); 3) receptive language skills; 4) speech development; 5) cognitive development; 6) psychosocial skills; 7) listening skills; 8) generic health-related quality of life; 9) parental stress; 10) vestibular function; 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for key outcomes. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method, due to challenges in interpreting the results of mean hearing thresholds., Main Results: We included 19 RCTs (2888 children). We considered most of the evidence to be very uncertain, due to wide confidence intervals for the effect estimates, few participants, and a risk of performance and detection bias. Here we report our key outcomes at the longest reported follow-up. There were some limitations to the evidence. No studies investigated the comparison of ventilation tubes versus hearing aids. We did not identify any data on disease-specific quality of life; however, many studies were conducted before the development of specific tools to assess this in otitis media. Short-acting ventilation tubes were used in most studies and thus specific data on the use of long-acting VTs is limited. Finally, we did not identify specific data on the effects of VTs in children at increased risk of OME (e.g. with craniofacial syndromes). Ventilation tubes versus no treatment (four studies) The odds ratio (OR) for a return to normal hearing after 12 months was 1.13 with VTs (95% confidence interval (CI) 0.46 to 2.74; 54% versus 51%; 1 study, 72 participants; very low-certainty evidence). At six months, VTs may lead to a large reduction in persistent OME (risk ratio (RR) 0.30, 95% CI 0.14 to 0.65; 20.4% versus 68.0%; 1 study, 54 participants; low-certainty evidence). The evidence is very uncertain about the chance of persistent tympanic membrane perforation with VTs at 12 months (OR 0.85, 95% CI 0.38 to 1.91; 8.3% versus 9.7%; 1 RCT, 144 participants). Early ventilation tubes versus watchful waiting (six studies) There was little to no difference in the proportion of children whose hearing returned to normal after 8 to 10 years (i.e. by the age of 9 to 13 years) (RR for VTs 0.98, 95% CI 0.94 to 1.03; 93% versus 95%; 1 study, 391 participants; very low-certainty evidence). VTs may also result in little to no difference in the risk of persistent OME after 18 months to 6 years (RR 1.21, 95% CI 0.84 to 1.74; 15% versus 12%; 3 studies, 584 participants; very low-certainty evidence). We were unable to pool data on persistent perforation. One study showed that VTs may increase the risk of perforation after a follow-up duration of 3.75 years (RR 3.65, 95% CI 0.41 to 32.38; 1 study, 391 participants; very low-certainty evidence) but the actual number of children who develop persistent perforation may be low, as demonstrated by another study (1.26%; 1 study, 635 ears; very low-certainty evidence). Ventilation tubes versus non-surgical treatment (one study) One study compared VTs to six months of antibiotics (sulphisoxazole). No data were available on return to normal hearing, but final hearing thresholds were reported. At four months, the mean difference was -5.98 dB HL lower (better) for those receiving VTs, but the evidence is very uncertain (95% CI -9.21 to -2.75; 1 study, 125 participants; very low-certainty evidence). No evidence was identified regarding persistent OME. VTs may result in a low risk of persistent perforation at 18 months of follow-up (no events reported; narrative synthesis of 1 study, 60 participants; low-certainty evidence). Ventilation tubes versus myringotomy (nine studies) We are uncertain whether VTs may slightly increase the likelihood of returning to normal hearing at 6 to 12 months, since the confidence intervals were wide and included the possibility of no effect (RR 1.22, 95% CI 0.59 to 2.53; 74% versus 64%; 2 studies, 132 participants; very low-certainty evidence). After six months, persistent OME may be reduced for those who receive VTs compared to laser myringotomy, but the evidence is very uncertain (OR 0.27, 95% CI 0.19 to 0.38; 1 study, 272 participants; very low-certainty evidence). At six months, the risk of persistent perforation is probably similar with the use of VTs or laser myringotomy (narrative synthesis of 6 studies, 581 participants; moderate-certainty evidence)., Authors' Conclusions: There may be small short- and medium-term improvements in hearing and persistence of OME with VTs, but it is unclear whether these persist after longer follow-up. The RCTs included do not allow us to say when (or how much) VTs improve hearing in any specific child. However, interpretation of the evidence is difficult: many children in the control groups recover spontaneously or receive VTs during follow-up, VTs may block or extrude, and OME may recur. The limited evidence in this review also affects the generalisability/applicability of our findings to situations involving children with underlying conditions (e.g. craniofacial syndromes) or the use of long-acting tubes. Consequently, RCTs may not be the best way to determine whether an intervention is likely to be effective in any individual child. Instead, we must better understand the different OME phenotypes to target interventions to children who will benefit most, and avoid over-treating when spontaneous resolution is likely., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Competing Interests: Competing interests: We declared the following interests based on NICE’s policy on conflicts of interests (https://www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/declaration-of-interests-policy.pdf): Jennifer Royds is a trustee and founder of a charity called Glue Ear Together. The guideline authors’ full statements can be viewed at https://www.nice.org.uk/guidance/indevelopment/gid-ng10193/documents

Purpose: The purpose of this study was to evaluate whether the lung ultrasound (LUS) scores applied to an international cohort of patients presenting to the emergency department (ED) with suspected COVID-19, and subsequently admitted with proven disease, could prognosticate clinical outcomes., Methods: This was an international, multicentre, prospective, observational cohort study of patients who received LUS and were followed for the composite primary outcome of intubation, intensive care unit (ICU) admission or death. LUS scores were later applied including two 12-zone protocols ('de Alencar score' and 'CLUE score'), a 12-zone protocol with lung and pleural findings ('Ji score') and an 11-zone protocol ('Tung-Chen score'). The primary analysis comprised logistic regression modelling of the composite primary outcome, with the LUS scores analysed individually as predictor variables., Results: Between April 2020 to April 2022, 129 patients with COVID-19 had LUS performed according to the protocol and 24 (18.6%) met the composite primary endpoint. No association was seen between the LUS score and the composite primary end point for the de Alencar score [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97-1.11; P = 0.29], the CLUE score (OR = 1.03; 95% CI: 0.96-1.10; P = 0.40), the Ji score (OR = 1.02; 95% CI: 0.97-1.07; P = 0.40) or the Tung-Chen score (OR = 1.02; 95% CI: 0.97-1.08)., Discussion: Compared to these earlier studies performed at the start of the pandemic, the negative outcome of our study could reflect the changing scenario of the COVID-19 pandemic, including patient, disease, and system factors. The analysis suggests that the study may have been underpowered to detect a weaker association between a LUS score and the primary outcome., Conclusion: In an international cohort of adult patients presenting to the ED with suspected COVID-19 disease who had LUS performed and were subsequently admitted to hospital, LUS severity scores did not prognosticate the need for invasive ventilation, ICU admission or death., Competing Interests: None to declare., (© 2023 The Authors. Australasian Journal of Ultrasound in Medicine published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Ultrasound in Medicine.)

Background: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Adenoidectomy has often been used as a potential treatment for this condition., Objectives: To assess the benefits and harms of adenoidectomy, either alone or in combination with ventilation tubes (grommets), for OME in children., Search Methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 January 2023., Selection Criteria: Randomised controlled trials and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared adenoidectomy (alone, or in combination with ventilation tubes) with either no treatment or non-surgical treatment., Data Collection and Analysis: We used standard Cochrane methods. Primary outcomes (determined following a multi-stakeholder prioritisation exercise): 1) hearing, 2) otitis media-specific quality of life, 3) haemorrhage., Secondary Outcomes: 1) persistence of OME, 2) adverse effects, 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial skills, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function, 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds., Main Results: We included 10 studies (1785 children). Many of the studies used concomitant interventions for all participants, including insertion of ventilation tubes or myringotomy. All included studies had at least some concerns regarding the risk of bias. We report results for our main outcome measures at the longest available follow-up. We did not identify any data on disease-specific quality of life for any of the comparisons. Further details of additional outcomes and time points are reported in the review. 1) Adenoidectomy (with or without myringotomy) versus no treatment/watchful waiting (three studies) After 12 months there was little difference in the proportion of children whose hearing had returned to normal, but the evidence was very uncertain (adenoidectomy 68%, no treatment 70%; risk ratio (RR) 0.97, 95% confidence interval (CI) 0.65 to 1.46; number needed to treat to benefit (NNTB) 50; 1 study, 42 participants). There is a risk of haemorrhage from adenoidectomy, but the absolute risk appears small (1/251 receiving adenoidectomy compared to 0/229, Peto odds ratio (OR) 6.77, 95% CI 0.13 to 342.54; 1 study, 480 participants; moderate certainty evidence). The risk of persistent OME may be slightly lower after two years in those receiving adenoidectomy (65% versus 73%), but again the difference was small (RR 0.90, 95% CI 0.81 to 1.00; NNTB 13; 3 studies, 354 participants; very low-certainty evidence). 2) Adenoidectomy (with or without myringotomy) versus non-surgical treatment No studies were identified for this comparison. 3) Adenoidectomy and bilateral ventilation tubes versus bilateral ventilation tubes (four studies) There was a slight increase in the proportion of ears with a return to normal hearing after six to nine months (57% adenoidectomy versus 42% without, RR 1.36, 95% CI 0.98 to 1.89; NNTB 7; 1 study, 127 participants (213 ears); very low-certainty evidence). Adenoidectomy may give an increased risk of haemorrhage, but the absolute risk appears small, and the evidence was uncertain (2/416 with adenoidectomy compared to 0/375 in the control group, Peto OR 6.68, 95% CI 0.42 to 107.18; 2 studies, 791 participants). The risk of persistent OME was similar for both groups (82% adenoidectomy and ventilation tubes compared to 85% ventilation tubes alone, RR 0.96, 95% CI 0.86 to 1.07; very low-certainty evidence). 4) Adenoidectomy and unilateral ventilation tube versus unilateral ventilation tube (two studies) Slightly more children returned to normal hearing after adenoidectomy, but the confidence intervals were wide (57% versus 46%, RR 1.24, 95% CI 0.79 to 1.96; NNTB 9; 1 study, 72 participants; very low-certainty evidence). Fewer children may have persistent OME after 12 months, but again the confidence intervals were wide (27.2% compared to 40.5%, RR 0.67, 95% CI 0.35 to 1.29; NNTB 8; 1 study, 74 participants). We did not identify any data on haemorrhage. 5) Adenoidectomy and ventilation tubes versus no treatment/watchful waiting (two studies) We did not identify data on the proportion of children who returned to normal hearing. However, after two years, the mean difference in hearing threshold for those allocated to adenoidectomy was -3.40 dB (95% CI -5.54 to -1.26; 1 study, 211 participants; very low-certainty evidence). There may be a small reduction in the proportion of children with persistent OME after two years, but the evidence was very uncertain (82% compared to 90%, RR 0.91, 95% CI 0.82 to 1.01; NNTB 13; 1 study, 232 participants). We noted that many children in the watchful waiting group had also received surgery by this time point. 6) Adenoidectomy and ventilation tubes versus non-surgical treatment No studies were identified for this comparison., Authors' Conclusions: When assessed with the GRADE approach, the evidence for adenoidectomy in children with OME is very uncertain. Adenoidectomy may reduce the persistence of OME, although evidence about the effect of this on hearing is unclear. For patients and carers, a return to normal hearing is likely to be important, but few studies measured this outcome. We did not identify any evidence on disease-specific quality of life. There were few data on adverse effects, in particular postoperative bleeding. The risk of haemorrhage appears to be small, but should be considered when choosing a treatment strategy for children with OME. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Antibiotics are sometimes used to treat any bacteria present in the effusion, or associated biofilms., Objectives: To assess the effects (benefits and harms) of oral antibiotics for otitis media with effusion (OME) in children., Search Methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished studies to 20 January 2023., Selection Criteria: We included randomised controlled trials and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared oral antibiotics with either placebo or no treatment., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were determined following a multi-stakeholder prioritisation exercise and were: 1) hearing, 2) otitis media-specific quality of life and 3) anaphylaxis. Secondary outcomes were: 1) persistence of OME, 2) adverse effects, 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial skills, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function and 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds., Main Results: We identified 19 completed studies that met our inclusion criteria (2581 participants). They assessed a variety of oral antibiotics (including penicillins, cephalosporins, macrolides and trimethoprim), with most studies using a 10- to 14-day treatment course. We had some concerns about the risk of bias in all studies included in this review. Here we report our primary outcomes and main secondary outcome, at the longest reported follow-up time. Antibiotics versus placebo We included 11 studies for this comparison, but none reported all of our outcomes of interest and limited meta-analysis was possible. Hearing One study found that more children may return to normal hearing by two months (resolution of the air-bone gap) after receiving antibiotics as compared with placebo, but the evidence is very uncertain (Peto odds ratio (OR) 9.59, 95% confidence interval (CI) 3.51 to 26.18; 20/49 children who received antibiotics returned to normal hearing versus 0/37 who received placebo; 1 study, 86 participants; very low-certainty evidence). Disease-specific quality of life No studies assessed this outcome. Presence/persistence of OME At 6 to 12 months of follow-up, the use of antibiotics compared with placebo may slightly reduce the number of children with persistent OME, but the confidence intervals were wide, and the evidence is very uncertain (risk ratio (RR) 0.89, 95% CI 0.68 to 1.17; 48% versus 54%; number needed to treat (NNT) 17; 2 studies, 324 participants; very low-certainty evidence). Adverse event: anaphylaxis No studies provided specific data on anaphylaxis. Three of the included studies (448 children) did report adverse events in sufficient detail to assume that no anaphylactic reactions occurred, but the evidence is very uncertain (very low-certainty evidence). Antibiotics versus no treatment We included eight studies for this comparison, but very limited meta-analysis was possible. Hearing One study found that the use of antibiotics compared to no treatment may result in little to no difference in final hearing threshold at three months (mean difference (MD) -5.38 dB HL, 95% CI -9.12 to -1.64; 1 study, 73 participants; low-certainty evidence). The only data identified on the return to normal hearing were reported at 10 days of follow-up, which we considered to be too short to accurately reflect the efficacy of antibiotics. Disease-specific quality of life No studies assessed this outcome. Presence/persistence of OME Antibiotics may reduce the proportion of children who have persistent OME at up to three months of follow-up, when compared with no treatment (RR 0.64, 95% CI 0.50 to 0.80; 6 studies, 542 participants; low-certainty evidence). Adverse event: anaphylaxis No studies provided specific data on anaphylaxis. Two of the included studies (180 children) did report adverse events in sufficient detail to assume that no anaphylactic reactions occurred, but the evidence is very uncertain (very low-certainty evidence)., Authors' Conclusions: The evidence for the use of antibiotics for OME is of low to very low certainty. Although the use of antibiotics compared to no treatment may have a slight beneficial effect on the resolution of OME at up to three months, the overall impact on hearing is very uncertain. The long-term effects of antibiotics are unclear and few of the studies included in this review reported on potential harms. These important endpoints should be considered when weighing up the potential short- and long-term benefits and harms of antibiotic treatment in a condition with a high spontaneous resolution rate., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Social workers have been at the forefront of research and advocacy to improve nursing home care for several decades. However, United States (U.S.) regulations have not kept pace with professional standards, as nursing home social services workers are still not required to have a degree in social work and many are assigned caseloads that are untenable for providing quality psychosocial and behavioral health care. The National Academies of Sciences, Engineering, and Medicine (NASEM)'s recently published interdisciplinary consensus report, The National Imperative to Improve Nursing Home Quality: Honoring our Commitment to Residents, Families, and Staff (NASEM, 2022) makes recommendations for changing these regulations, reflecting years of social work scholarship and policy advocacy. In this commentary, we highlight the NASEM report recommendations for social work and chart a course for continuing scholarship and policy advocacy to improve resident outcomes.

Objective: Interstitial lung disease (ILD) is relatively common in patients with lung cancer with an incidence of 7.5%. Historically pre-existing ILD was a contraindication to radical radiotherapy owing to increased radiation pneumonitis rates, worsened fibrosis and poorer survival compared with non-ILD cohorts. Herein, the clinical and radiological toxicity outcomes of a contemporaneous cohort are described., Methods: Patients with ILD treated with radical radiotherapy for lung cancer at a regional cancer centre were collected prospectively. Radiotherapy planning, tumour characteristics, and pre- and post-treatment functional and radiological parameters were recorded. Cross-sectional images were independently assessed by two Consultant Thoracic Radiologists., Results: Twenty-seven patients with co-existing ILD received radical radiotherapy from February 2009 to April 2019, with predominance of usual interstitial pneumonia subtype (52%). According to ILD-GAP scores, most patients were Stage I. After radiotherapy, localised (41%) or extensive (41%) progressive interstitial changes were noted for most patients yet dyspnoea scores ( n = 15 available) and spirometry ( n = 10 available) were stable. One-third of patients with ILD went on to receive long-term oxygen therapy, which was significantly more than the non-ILD cohort. Median survival trended towards being worse compared with non-ILD cases (17.8 vs 24.0 months, p = 0.834)., Conclusion: Radiological progression of ILD and reduced survival were observed post-radiotherapy in this small cohort receiving lung cancer radiotherapy, although a matched functional decline was frequently absent. Although there is an excess of early deaths, long-term disease control is achievable., Advances in Knowledge: For selected patients with ILD, long-term lung cancer control without severely impacting respiratory function may be possible with radical radiotherapy, albeit with a slightly higher risk of death., (© 2023 The Authors. Published by the British Institute of Radiology.)

Since the start of the COVID-19 pandemic in early 2020, governments around the world have adopted an array of measures intended to control the transmission of the SARS-CoV-2 virus, using both pharmaceutical and non-pharmaceutical interventions (NPIs). NPIs are public health interventions that do not rely on vaccines or medicines and include policies such as lockdowns, stay-at-home orders, school closures, and travel restrictions. Although the intention was to slow viral transmission, emerging research indicates that these NPIs have also had unintended consequences for other aspects of public health. Hence, we conducted a narrative review of studies investigating these unintended consequences of NPIs, with a particular emphasis on mental health and on lifestyle risk factors for non-communicable diseases (NCD): physical activity (PA), overweight and obesity, alcohol consumption, and tobacco smoking. We reviewed the scientific literature using combinations of search terms such as 'COVID-19', 'pandemic', 'lockdowns', 'mental health', 'physical activity', and 'obesity'. NPIs were found to have considerable adverse consequences for mental health, physical activity, and overweight and obesity. The impacts on alcohol and tobacco consumption varied greatly within and between studies. The variability in consequences for different groups implies increased health inequalities by age, sex/gender, socioeconomic status, pre-existing lifestyle, and place of residence. In conclusion, a proper assessment of the use of NPIs in attempts to control the spread of the pandemic should be weighed against the potential adverse impacts on other aspects of public health. Our findings should also be of relevance for future pandemic preparedness and pandemic response teams.

Substantial evidence suggests that access to urban green spaces and parks is associated with positive health outcomes, including decreased mortality. Few existing studies have investigated the association between green spaces and life expectancy (LE), and none have used small-area data in the U.S. Here we used the recently released U.S. Small-Area Life Expectancy Estimates Project data to quantify the relationship between LE and green space in Los Angeles County, a large diverse region with inequities in park access. We developed a model to quantify the association between green space and LE at the census tract level. We evaluated three green space metrics: normalized difference vegetation index (NDVI, 0.6-meter scale), percent tree canopy cover, and accessible park acres. We statistically adjusted for 15 other determinants of LE. We also developed conditional autoregressive models to account for spatial dependence. Tree canopy and NDVI were both significantly associated with higher LE. For an interquartile range (IQR) increase in each metric respectively, the spatial models demonstrated a 0.24 to 0.33-year increase in LE. Tree canopy and NDVI also modified the effect of park acreage on LE. ln areas with tree canopy levels below the county median, an IQR increase in park acreage was associated with an increase of 0.12 years. Although on an individual level these effects were modest, we predicted 155,300 years of LE gains across the population in LA County if all areas below median tree canopy were brought to the county median of park acres. If tree canopy or NDVI were brought to median levels, between 570,300 and 908,800 years of LE could be gained. The majority of potential gains are in areas with predominantly Hispanic/Latinx and Black populations. These findings suggest that equitable access to green spaces could result in substantial population health benefits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The increasing number and severity of wildfires is negatively impacting air quality for millions of California residents each year. Community exposure to PM 2.5 in two main population centers (San Francisco Bay area and Los Angeles County area) was assessed using the low-cost PurpleAir sensor network for the record-setting 2020 California wildfire season. Estimated PM 2.5 concentrations in each study area were compared to census tract-level environmental justice vulnerability indicators, including environmental, health, and demographic data. Higher PM 2.5 concentrations were positively correlated with poverty, cardiovascular emergency department visits, and housing inequities. Sensors within 30 km of actively burning wildfires showed statistically significant increases in indoor (~800 %) and outdoor (~540 %) PM 2.5 during the fires. Results indicate that wildfire emissions may exacerbate existing health disparities as well as the burden of pollution in disadvantaged communities, suggesting a need to improve monitoring and adaptive capacity among vulnerable populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced or appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Effective self-care is an important factor in the successful management of patients with heart failure (HF). Despite the importance of self-care, most patients with HF are not adequately taught the wide range of skills required to become proficient in self-care. Digital health technology (DHT) may provide a novel solution to support patients at home in effective self-care, with the view to enhancing the quality of life and ultimately improving patient outcomes. However, many of the solutions developed to date have failed to consider users' perspectives at the point of design, resulting in poor effectiveness. Leveraging a human-centered design (HCD) approach to the development of DHTs may lead to the successful promotion of self-care behaviors in patients with HF., Objective: This study aimed to outline the HCD, development, and evaluation process of a DHT designed to promote effective self-care in patients with HF., Methods: A design thinking approach within the HCD framework was undertaken, as described in the International Organization for Standardization 9241-210:2019 regulations, using a 5-step process: empathize, ideate, design, develop, and test. Patients with HF were involved throughout the design and evaluation of the system. The designed system was grounded in behavior change theory using the Theoretical Domains Framework and included behavior change techniques. Mixed methods were used to evaluate the DHT during the testing phase., Results: Steps 1 to 3 of the process resulted in a set of evidence- and user-informed design requirements that were carried forward into the iterative development of a version 1 system. A cross-platform (iOS and Android) mobile app integrated with Fitbit activity trackers and smart scales was developed. A 2-week user testing phase highlighted the ease of use of the system, with patients demonstrating excellent adherence. Qualitative analysis of semistructured interviews identified the early potential for the system to positively influence self-care. Specifically, users perceived that the system increased their confidence and motivation to engage in key self-care behaviors, provided them with skills and knowledge that made them more aware of the importance of self-care behaviors, and might facilitate timely help seeking., Conclusions: The use of an HCD methodology in this research has resulted in the development of a DHT that may engage patients with HF and potentially affect their self-care behaviors. This comprehensive work lays the groundwork for further development and evaluation of this solution before its implementation in health care systems. A detailed description of the HCD process used in this research will help guide the development and evaluation of future DHTs across a range of disease use cases., (©William Johnston, Alison Keogh, Jane Dickson, Stephen J Leslie, Peter Megyesi, Rachelle Connolly, David Burke, Brian Caulfield. Originally published in JMIR Formative Research (https://formative.jmir.org), 10.05.2022.)

Many patients discontinue endocrine therapy for breast cancer due to intolerance. Identification of patients at risk for discontinuation is challenging. The minimal important difference (MID) is the smallest change in a score on a patient-reported outcome (PRO) that is clinically significant. We evaluated the association between treatment-emergent symptoms detected by worsening PRO scores in units equal to the MID with discontinuation. We enrolled females with stage 0-III breast cancer initiating endocrine therapy in a prospective cohort. Participants completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance; Endocrine Subscale of the FACT-ES; and MOS-Sexual Problems (MOS-SP). We evaluated associations between continuous PRO scores in units corresponding to MIDs (PROMIS: 4-points; FACT-ES: 5-points; MOS-SP: 8-points) with time to endocrine therapy discontinuation using Cox proportional hazards models. Among 321 participants, 140 (43.6%) initiated tamoxifen and 181 (56.4%) initiated aromatase inhibitor (AI). The cumulative probability of discontinuation was 23% (95% CI 18-27%) at 48 months. For every 5- and 4-point worsening in endocrine symptoms and sleep disturbance respectively, participants were 13 and 14% more likely to discontinue endocrine therapy respectively (endocrine symptoms HR 1.13, 95% CI 1.02-1.25, p = 0.02; sleep disturbance HR 1.14, 95% CI 1.01-1.29, p = 0.03). AI treatment was associated with greater likelihood of discontinuation than tamoxifen. Treatment-emergent endocrine symptoms and sleep disturbance are associated with endocrine therapy discontinuation. Monitoring for worsening scores meeting or exceeding the MID on PROs may identify patients at risk for discontinuation., (© 2022. The Author(s).)

Blood-brain barrier (BBB) dysfunction is associated with worse epilepsy outcomes however the underlying molecular mechanisms of BBB dysfunction remain to be elucidated. Tight junction proteins are important regulators of BBB integrity and in particular, the tight junction protein claudin-5 is the most enriched in brain endothelial cells and regulates size-selectivity at the BBB. Additionally, disruption of claudin-5 expression has been implicated in numerous disorders including schizophrenia, depression and traumatic brain injury, yet its role in epilepsy has not been fully deciphered. Here we report that claudin-5 protein levels are significantly diminished in surgically resected brain tissue from patients with treatment-resistant epilepsy. Concomitantly, dynamic contrast-enhanced MRI in these patients showed widespread BBB disruption. We show that targeted disruption of claudin-5 in the hippocampus or genetic heterozygosity of claudin-5 in mice exacerbates kainic acid-induced seizures and BBB disruption. Additionally, inducible knockdown of claudin-5 in mice leads to spontaneous recurrent seizures, severe neuroinflammation, and mortality. Finally, we identify that RepSox, a regulator of claudin-5 expression, can prevent seizure activity in experimental epilepsy. Altogether, we propose that BBB stabilizing drugs could represent a new generation of agents to prevent seizure activity in epilepsy patients., (© 2022. The Author(s).)

Aim: This systematic review aims to evaluate the current body of research surrounding the efficacy of artificial intelligence (AI) in cardiac rehabilitation. Presently, AI can be incorporated into personal devices such as smart watches and smartphones, in diagnostic and home monitoring devices, as well as in certain inpatient care settings. Materials & methods: The PRISMA guidelines were followed in this review. Inclusion and exclusion criteria were set using the Population, Intervention, Comparison and Outcomes (PICO) tool. Results: Eight studies meeting the inclusion criteria were found. Conclusion: Incorporation of AI into healthcare, cardiac rehabilitation delivery, and monitoring holds great potential for early detection of cardiac events, allowing for home-based monitoring, and improved clinician decision making.