Reporting quality of published reviews of commercial and publicly available mobile health apps (mHealth app reviews): a scoping review protocol.

INTRODUCTION: Reviews of commercial and publicly available smartphone (mobile) health applications (mHealth app reviews) are being undertaken and published. However, there is variation in the conduct and reporting of mHealth app reviews, with no existing reporting guidelines. Building on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we aim to develop the Consensus for APP Review Reporting Items (CAPPRRI) guidance, to support the conduct and reporting of mHealth app reviews. This scoping review of published mHealth app reviews will explore their alignment, deviation, and modification to the PRISMA 2020 items for systematic reviews and identify a list of possible items to include in CAPPRRI. METHOD AND ANALYSIS: We are following the Joanna Briggs Institute approach and Arksey and O'Malley's five-step process. Patient and public contributors, mHealth app review, digital health research and evidence synthesis experts, healthcare professionals and a specialist librarian gave feedback on the methods. We will search SCOPUS, CINAHL Plus, AMED, EMBASE, Medline, APA PsycINFO and the ACM Digital Library for articles reporting mHealth app reviews and use a two-step screening process to identify eligible articles. Information on whether the authors have reported, or how they have modified the PRISMA 2020 items in their reporting, will be extracted. Data extraction will also include the article characteristics, protocol and registration information, review question frameworks used, information about the search and screening process, how apps have been evaluated and evidence of stakeholder engagement. This will be analysed using a content synthesis approach and presented using descriptive statistics and summaries. This protocol is registered on OSF (https://osf.io/5ahjx). ETHICS AND DISSEMINATION: Ethical approval is not required. The findings will be disseminated through peer-reviewed journal publications (shared on our project website and on the EQUATOR Network website where the CAPPRRI guidance has been registered as under development), conference presentations and blog and social media posts in lay language.

Type IV-A3 CRISPR-Cas systems drive inter-plasmid conflicts by acquiring spacers in trans.

Plasmid-encoded type IV-A CRISPR-Cas systems lack an acquisition module, feature a DinG helicase instead of a nuclease, and form ribonucleoprotein complexes of unknown biological functions. Type IV-A3 systems are carried by conjugative plasmids that often harbor antibiotic-resistance genes and their CRISPR array contents suggest a role in mediating inter-plasmid conflicts, but this function remains unexplored. Here, we demonstrate that a plasmid-encoded type IV-A3 system co-opts the type I-E adaptation machinery from its host, Klebsiella pneumoniae (K. pneumoniae), to update its CRISPR array. Furthermore, we reveal that robust interference of conjugative plasmids and phages is elicited through CRISPR RNA-dependent transcriptional repression. By silencing plasmid core functions, type IV-A3 impacts the horizontal transfer and stability of targeted plasmids, supporting its role in plasmid competition. Our findings shed light on the mechanisms and ecological function of type IV-A3 systems and demonstrate their practical efficacy for countering antibiotic resistance in clinically relevant strains.

California's 2023 snow deluge: Contextualizing an extreme snow year against future climate change.

The increasing prevalence of low snow conditions in a warming climate has attracted substantial attention in recent years, but a focus exclusively on low snow leaves high snow years relatively underexplored. However, these large snow years are hydrologically and economically important in regions where snow is critical for water resources. Here, we introduce the term "snow deluge" and use anomalously high snowpack in California's Sierra Nevada during the 2023 water year as a case study. Snow monitoring sites across the state had a median 41 y return interval for April 1 snow water equivalent (SWE). Similarly, a process-based snow model showed a 54 y return interval for statewide April 1 SWE (90% CI: 38 to 109 y). While snow droughts can result from either warm or dry conditions, snow deluges require both cool and wet conditions. Relative to the last century, cool-season temperature and precipitation during California's 2023 snow deluge were both moderately anomalous, while temperature was highly anomalous relative to recent climatology. Downscaled climate models in the Shared Socioeconomic Pathway-370 scenario indicate that California snow deluges-which we define as the 20 y April 1 SWE event-are projected to decline with climate change (58% decline by late century), although less so than median snow years (73% decline by late century). This pattern occurs across the western United States. Changes to snow deluge, and discrepancies between snow deluge and median snow year changes, could impact water resources and ecosystems. Understanding these changes is therefore critical to appropriate climate adaptation.

Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

What works to support carers of older people and older carers? an international evidence map of interventions and outcomes.

BACKGROUND: Unpaid carers of older people, and older unpaid carers, experience a range of adverse outcomes. Supporting carers should therefore be a public health priority. Our understanding of what works to support carers could be enhanced if future evaluations prioritise under-researched interventions and outcomes. To support this, we aimed to: map evidence about interventions to support carers, and the outcomes evaluated; and identify key gaps in current evidence. METHODS: Evidence gap map review methods were used. Searches were carried out in three bibliographic databases for quantitative evaluations of carer interventions published in OECD high-income countries between 2013 and 2023. Interventions were eligible if they supported older carers (50 + years) of any aged recipient, or any aged carers of older people (50 + years). FINDINGS: 205 studies reported across 208 publications were included in the evidence map. The majority evaluated the impact of therapeutic and educational interventions on carer burden and carers' mental health. Some studies reported evidence about physical exercise interventions and befriending and peer support for carers, but these considered a limited range of outcomes. Few studies evaluated interventions that focused on delivering financial information and advice, pain management, and physical skills training for carers. Evaluations rarely considered the impact of interventions on carers' physical health, quality of life, and social and financial wellbeing. Very few studies considered whether interventions delivered equitable outcomes. CONCLUSION: Evidence on what works best to support carers is extensive but limited in scope. A disproportionate focus on mental health and burden outcomes neglects other important areas where carers may need support. Given the impact of caring on carers' physical health, financial and social wellbeing, future research could evaluate interventions that aim to support these outcomes. Appraisal of whether interventions deliver equitable outcomes across diverse carer populations is critical.

Barriers to and Facilitators of Older People's Engagement With Web-Based Services: Qualitative Study of Adults Aged >75 Years.

BACKGROUND: The COVID-19 pandemic has accelerated the shift toward the digital provision of many public services, including health and social care, public administration, and financial and leisure services. COVID-19 services including test appointments, results, vaccination appointments and more were primarily delivered through digital channels to the public. Many social, cultural, and economic activities (appointments, ticket bookings, tax and utility payments, shopping, etc) have transitioned to web-based platforms. To use web-based public services, individuals must be digitally included. This is influenced by 3 main factors: access (whether individuals have access to the internet), ability (having the requisite skills and confidence to participate over the web), and affordability (ability to pay for infrastructure [equipment] and data packages). Many older adults, especially those aged >75 years, are still digitally excluded. OBJECTIVE: This study aims to explore the views of adults aged >75 years on accessing public services digitally. METHODS: We conducted semistructured qualitative interviews with a variety of adults aged ≥75 years residing in Greater Manchester, United Kingdom. We also interviewed community support workers. Thematic analysis was used to identify the key themes from the data. RESULTS: Overall, 24 older adults (mean age 81, SD 4.54 y; 14/24, 58% female; 23/24, 96% White British; and 18/24, 75% digitally engaged to some extent) and 2 support workers participated. A total of five themes were identified as key in understanding issues around motivation, engagement, and participation: (1) "initial motivation to participate digitally"-for example, maintaining social connections and gaining skills to be able to connect with family and friends; (2) "narrow use and restricted activity on the web"-undertaking limited tasks on the web and in a modified manner, for example, limited use of web-based public services and selected use of specific services, such as checking but never transferring funds during web-based banking; (3) "impact of digital participation on well-being"-choosing to go to the shops or general practitioner's surgery to get out of the house and get some exercise; (4) "the last generation?"-respondents feeling that there were generational barriers to adapting to new technology and change; and (5) "making digital accessible"-understanding the support needed to keep those engaged on the web. CONCLUSIONS: As we transition toward greater digitalization of public services, it is crucial to incorporate the perspectives of older people. Failing to do so risks excluding them from accessing services they greatly rely on and need.

Digital technologies to prevent falls in people living with dementia or mild cognitive impairment: a rapid systematic overview of systematic reviews.

OBJECTIVE: Falls are a common cause of potentially preventable death, disability and loss of independence with an annual estimated cost of £4.4bn. People living with dementia (PlwD) or mild cognitive impairment (MCI) have an increased fall risk. This overview evaluates evidence for technologies aiming to reduce falls and fall risk for PlwD or MCI. METHODS: In October 2022, we searched five databases for evidence syntheses. We used standard methods to rapidly screen, extract data, assess risk of bias and overlap, and synthesise the evidence for each technology type. RESULTS: We included seven systematic reviews, incorporating 22 relevant primary studies with 1,412 unique participants. All reviews had critical flaws on AMSTAR-2: constituent primary studies were small, heterogeneous, mostly non-randomised and assessed as low or moderate quality. Technologies assessed were: wearable sensors, environmental sensor-based systems, exergaming, virtual reality systems. We found no evidence relating to apps. Review evidence for the direct impact on falls was available only from environmental sensors, and this was inconclusive. For wearables and virtual reality technologies there was evidence that technologies may differentiate PlwD who fell from those who did not; and for exergaming that balance may be improved. CONCLUSIONS: The evidence for technology to reduce falls and falls risk for PlwD and MCI is methodologically weak, based on small numbers of participants and often indirect. There is a need for higher-quality RCTs to provide robust evidence for effectiveness of fall prevention technologies. Such technologies should be designed with input from users and consideration of the wider implementation context.

Identifying Obstructive Sleep Apnea Risk Using the STOP-BANG Questionnaire in a Cardiology Clinic.

ABSTRACT: Untreated obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality, warranting enhanced awareness, screening, and action among healthcare providers to optimize patient outcomes. Attempting to address the potential under detection of OSA, this quality improvement project implemented the STOP-Bang Sleep Apnea Questionnaire at a cardiology clinic, with the goals to stratify risk for OSA in 100% of patients and increase provider referral of high risk patients for sleep studies. The setting was an outpatient cardiology clinic in Pensacola, Florida. The sample included new and existing patients 18 years or older who had one or more of the following diagnoses: hypertension, heart failure, coronary artery disease, atrial fibrillation, or arrhythmia. Methods involved collecting and comparing preintervention sleep study referral rate data with 6-week STOP-Bang questionnaire implementation data. Results demonstrated a 65% (279 of 428 patients seen) screening implementation rate and a modest but statistically significant increase in the overall referral rate from 2.6% preintervention to 5.1% postintervention ( p = .040). Overall, standard use of the STOP-Bang questionnaire may enable higher detection and referral of OSA.

Transitional Care Interventions From Hospital to Community to Reduce Health Care Use and Improve Patient Outcomes: A Systematic Review and Network Meta-Analysis.

Importance: Discharge from the hospital to the community has been associated with serious patient risks and excess service costs. Objective: To evaluate the comparative effectiveness associated with transitional care interventions with different complexity levels at improving health care utilization and patient outcomes in the transition from the hospital to the community. Data Sources: CENTRAL, Embase, MEDLINE, and PsycINFO were searched from inception until August 2022. Study Selection: Randomized clinical trials evaluating transitional care interventions from hospitals to the community were identified. Data Extraction and Synthesis: At least 2 reviewers were involved in all data screening and extraction. Random-effects network meta-analyses and meta-regressions were applied. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Main Outcomes and Measures: The primary outcomes were readmission at 30, 90, and 180 days after discharge. Secondary outcomes included emergency department visits, mortality, quality of life, patient satisfaction, medication adherence, length of stay, primary care and outpatient visits, and intervention uptake. Results: Overall, 126 trials with 97 408 participants were included, 86 (68%) of which were of low risk of bias. Low-complexity interventions were associated with the most efficacy for reducing hospital readmissions at 30 days (odds ratio [OR], 0.78; 95% CI, 0.66 to 0.92) and 180 days (OR, 0.45; 95% CI, 0.30 to 0.66) and emergency department visits (OR, 0.68; 95% CI, 0.48 to 0.96). Medium-complexity interventions were associated with the most efficacy at reducing hospital readmissions at 90 days (OR, 0.64; 95% CI, 0.45 to 0.92), reducing adverse events (OR, 0.42; 95% CI, 0.24 to 0.75), and improving medication adherence (standardized mean difference [SMD], 0.49; 95% CI, 0.30 to 0.67) but were associated with less efficacy than low-complexity interventions for reducing readmissions at 30 and 180 days. High-complexity interventions were most effective for reducing length of hospital stay (SMD, -0.20; 95% CI, -0.38 to -0.03) and increasing patient satisfaction (SMD, 0.52; 95% CI, 0.22 to 0.82) but were least effective for reducing readmissions at all time periods. None of the interventions were associated with improved uptake, quality of life (general, mental, or physical), or primary care and outpatient visits. Conclusions and Relevance: These findings suggest that low- and medium-complexity transitional care interventions were associated with reducing health care utilization for patients transitioning from hospitals to the community. Comprehensive and consistent outcome measures are needed to capture the patient benefits of transitional care interventions.

Clinical antibiotic-resistance plasmids have small effects on biofilm formation and population growth in Escherichia coli in vitro.

Antimicrobial resistance (AR) mechanisms encoded on plasmids can affect other phenotypic traits in bacteria, including biofilm formation. These effects may be important contributors to the spread of AR and the evolutionary success of plasmids, but it is not yet clear how common such effects are for clinical plasmids/bacteria, and how they vary among different plasmids and host strains. Here, we used a combinatorial approach to test the effects of clinical AR plasmids on biofilm formation and population growth in clinical and laboratory Escherichia coli strains. In most of the 25 plasmid-bacterium combinations tested, we observed no significant change in biofilm formation upon plasmid introduction, contrary to the notion that plasmids frequently alter biofilm formation. In a few cases we detected altered biofilm formation, and these effects were specific to particular plasmid-bacterium combinations. By contrast, we found a relatively strong effect of a chromosomal streptomycin-resistance mutation (in rpsL) on biofilm formation. Further supporting weak and host-strain-dependent effects of clinical plasmids on bacterial phenotypes in the combinations we tested, we found growth costs associated with plasmid carriage (measured in the absence of antibiotics) were moderate and varied among bacterial strains. These findings suggest some key clinical resistance plasmids cause only mild phenotypic disruption to their host bacteria, which may contribute to the persistence of plasmids in the absence of antibiotics.

Integrated Fluorescence Microscopy (iFLM) for Cryo-FIB-milling and In-situ Cryo-ET.

Correlative cryo-FLM-FIB milling is a powerful sample preparation technique for in situ cryo-ET. However, correlative workflows that incorporate precise targeting remain challenging. Here, we demonstrate the development and use of an integrated Fluorescence Light Microscope (iFLM) module within a cryo-FIB-SEM to enable a coordinate-based two-point 3D correlative workflow. The iFLM guided targeting of regions of interest coupled with an automated milling process of the cryo-FIB-SEM instrument allows for the efficient preparation of 9-12 ∼200 nm thick lamellae within 24 hours. Using regular and montage-cryo-ET data collection schemes, we acquired data from FIB-milled lamellae of HeLa cells to examine cellular ultrastructure. Overall, this workflow facilitates on-the-fly targeting and automated FIB-milling of cryo-preserved cells, bacteria, and possibly high pressure frozen tissue, to produce lamellae for downstream cryo-ET data collection.

Promoting sexual health in older adults: Findings from two rapid reviews.

BACKGROUND: Sexual health throughout the life course is increasingly recognised as important to maintaining one's overall health, wellbeing, and relationships. We aimed to provide an overview of the evidence on sexual health needs and sexual health promotion in later life. METHODS: We undertook two rapid reviews, drawing on systematic review evidence. Searches were conducted in Epistemonikos. Studies were eligible if they reported evidence about the sexual health needs of, or sexual health promotion interventions for, people aged 50+ years. Evidence was quality assessed and summarised in a narrative synthesis. RESULTS: Fifteen systematic reviews were included in Review 1 (sexual health needs) and 12 in Review 2 (interventions). Key concerns and needs of older adults included the impacts of cultural stigma/misperceptions, barriers to sexual expression, and a need for tailored support in a welcoming environment. Key concerns and needs of health and social care professionals included mixed attitudes towards and knowledge of later-life sexuality and a need for more training and education. Approaches to promoting sexual health in later life included training and workshops for care home professionals, education for older people at risk of/living with HIV, and interventions to address sexual health-related symptoms of menopause. Gaps in the evidence from current reviews and methodological issues in primary studies were identified. CONCLUSION: Older people have specific needs relating to their sexual health. Health and social care professionals working with older people may benefit from education/training around sexuality in later life. Evidence on effective interventions and strategies is limited.

Antibiotic-degrading resistance changes bacterial community structure via species-specific responses.

Some bacterial resistance mechanisms degrade antibiotics, potentially protecting neighbouring susceptible cells from antibiotic exposure. We do not yet understand how such effects influence bacterial communities of more than two species, which are typical in nature. Here, we used experimental multispecies communities to test the effects of clinically important pOXA-48-plasmid-encoded resistance on community-level responses to antibiotics. We found that resistance in one community member reduced antibiotic inhibition of other species, but some benefitted more than others. Further experiments with supernatants and pure-culture growth assays showed the susceptible species profiting most from detoxification were those that grew best at degraded antibiotic concentrations (greater than zero, but lower than the starting concentration). This pattern was also observed on agar surfaces, and the same species also showed relatively high survival compared to most other species during the initial high-antibiotic phase. By contrast, we found no evidence of a role for higher-order interactions or horizontal plasmid transfer in community-level responses to detoxification in our experimental communities. Our findings suggest carriage of an antibiotic-degrading resistance mechanism by one species can drastically alter community-level responses to antibiotics, and the identities of the species that profit most from antibiotic detoxification are predicted by their intrinsic ability to survive and grow at changing antibiotic concentrations.

First-in-human clinical trial of allogeneic, platelet-derived extracellular vesicles as a potential therapeutic for delayed wound healing.

The release of growth factors, cytokines and extracellular matrix modifiers by activated platelets is an important step in the process of healthy wound healing. Extracellular vesicles (EVs) released by activated platelets carry this bioactive cargo in an enriched form, and may therefore represent a potential therapeutic for the treatment of delayed wound healing, such as chronic wounds. While EVs show great promise in regenerative medicine, their production at clinical scale remains a critical challenge and their tolerability in humans is still to be fully established. In this work, we demonstrate that Ligand-based Exosome Affinity Purification (LEAP) chromatography can successfully isolate platelet EVs (pEVs) of clinical grade from activated platelets, which retain the regenerative properties of the parent cell. LEAP-isolated pEVs display the expected biophysical features of EV populations and transport essential proteins in wound healing processes, including insulin growth factor (IGF) and transforming growth factor beta (TGF-ß). In vitro studies show that pEVs induce proliferation and migration of dermal fibroblasts and increase dermal endothelial cells' angiogenic potential, demonstrating their wound healing potential. pEV treatment activates the ERK and Akt signalling pathways within recipient cells. In a first-in-human, double-blind, placebo-controlled, phase I clinical trial of healthy volunteer adults, designed primarily to assess safety in the context of wound healing, we demonstrate that injections of LEAP-purified pEVs in formulation buffer are safe and well tolerated (Plexoval II study, ACTRN12620000944932). As a secondary objective, biological activity in the context of wound healing rate was assessed. In this cohort of healthy participants, in which the wound bed would not be expected to be deficient in the bioactive cargo that pEVs carry, all wounds healed rapidly and completely and no difference in time to wound closure of the treated and untreated wounds was observed at the single dose tested. The outcomes of this study evidence that pEVs manufactured through the LEAP process can be injected safely in humans as a potential wound healing treatment, and warrant further study in clinical trials designed expressly to assess therapeutic efficacy in patients with delayed or disrupted wound healing.

Stakeholder perspectives on navigating the pediatric concussion experience: Exploring the needs for improved communication across the care continuum.

BACKGROUND: For children, the post-concussion return to school process is a critical step towards achieving positive health outcomes. The process requires integration between healthcare professionals, parents, and school personnel. OBJECTIVE: This research team conducted focus groups with stakeholders including parents, education personnel, school nurses, external healthcare providers (nurses) and athletic trainers to identify communication patterns between healthcare providers outside of the school setting and school personnel. METHODS: Data from focus groups were analyzed using a Thematic Analysis approach. Researchers used an inductive (bottom-up) coding process to describe semantic themes and utilized a critical realist epistemology. RESULTS: We identified four key themes within focus group data: (1) lack of effective communication between hospital and outpatient healthcare providers to school personnel; (2) parents who were strong advocates had improved communication with healthcare professionals and garnered more accommodations for their children; (3) non-school professionals and families were often confused about who the point of contact was at a given school; and (4) differing experiences for athletes vs. non-athletes. CONCLUSION: This study suggests gaps in communication between healthcare and school professionals when children return to school following a concussion. Improving communication between healthcare providers and school staff will require a multi-faceted approach.

Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH): Study protocol for a multi-centered two-arm randomized adaptive trial.

Background: Intracerebral hemorrhage (ICH) is a potentially devastating condition with elevated early mortality rates, poor functional outcomes, and high costs of care. Standard of care involves intensive supportive therapy to prevent secondary injury. To date, there is no randomized control study demonstrating benefit of early evacuation of supratentorial ICH. Methods: The Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) Trial was designed to evaluate the minimally invasive trans-sulcal parafascicular surgery (MIPS) approach, a technique for safe access to deep brain structures and ICH removal using the BrainPath® and Myriad® devices (NICO Corporation, Indianapolis, IN). ENRICH is a multi-centered, two-arm, randomized, adaptive comparative-effectiveness study, where patients are block randomized by ICH location and Glasgow Coma Score (GCS) to early ICH evacuation using MIPS plus standard guideline-based management vs. standard management alone to determine if MIPS results in improved outcomes defined by the utility-weighted modified Rankin score (UWmRS) at 180 days as the primary endpoint. Secondary endpoints include clinical and economic outcomes of MIPS using cost per quality-adjusted life years (QALYs). The inclusion and exclusion criteria aim to capture a broad group of patients with high risk of significant morbidity and mortality to determine optimal treatment strategy. Discussion: ENRICH will result in improved understanding of the benefit of MIPS for both lobar and deep ICH affecting the basal ganglia. The ongoing study will lead to Level-I evidence to guide clinicians treatment options in the management of acute treatment of ICH. Trial registration: This study is registered with clinicaltrials.gov (Identifier: NCT02880878).

Host-specific plasmid evolution explains the variable spread of clinical antibiotic-resistance plasmids.

Antibiotic resistance encoded on plasmids is a pressing global health problem. Predicting which plasmids spread in the long term remains very challenging, even though some key parameters influencing plasmid stability have been identified, such as plasmid growth costs and horizontal transfer rates. Here, we show these parameters evolve in a strain-specific way among clinical plasmids and bacteria, and this occurs rapidly enough to alter the relative likelihoods of different bacterium-plasmid combinations spreading. We used experiments with Escherichia coli and antibiotic-resistance plasmids isolated from patients, paired with a mathematical model, to track long-term plasmid stability (beyond antibiotic exposure). Explaining variable stability across six bacterium-plasmid combinations required accounting for evolutionary changes in plasmid stability traits, whereas initial variation of these parameters was a relatively poor predictor of long-term outcomes. Evolutionary trajectories were specific to particular bacterium-plasmid combinations, as evidenced by genome sequencing and genetic manipulation. This revealed epistatic (here, strain-dependent) effects of key genetic changes affecting horizontal plasmid transfer. Several genetic changes involved mobile elements and pathogenicity islands. Rapid strain-specific evolution can thus outweigh ancestral phenotypes as a predictor of plasmid stability. Accounting for strain-specific plasmid evolution in natural populations could improve our ability to anticipate and manage successful bacterium-plasmid combinations.

Community composition of bacteria isolated from Swiss banknotes varies depending on collection environment.

Humans interact constantly with surfaces and associated microbial communities in the environment. The factors shaping the composition of these communities are poorly understood: some proposed explanations emphasize the influence of local habitat conditions (niche-based explanations), while others point to geographic structure and the distance among sampled locations (dispersal-based explanations). However, the relative roles of these different drivers for microbial community assembly on human-associated surfaces are not clear. Here, we used a combination of sampling, sequencing (16S rRNA) and culturing to show that the composition of banknote-associated bacterial communities varies depending on the local collection environment. Using banknotes collected from various locations and types of shops across Switzerland, we found taxonomic diversity dominated by families such as Pseudomonadaceae and Staphylococcaceae, but with banknote samples from particular types of shops (especially butcher shops) having distinct community structure. By contrast, we found no evidence of geographic structure: similarity of community composition did not decrease with increasing distance among sampled locations. These results show that microbial communities associated with banknotes, one of the most commonly encountered and exchanged human-associated surfaces, can reflect the local environmental conditions (in this case, the type of shop), and the signal for this type of variation was stronger than that for geographic structure among the locations sampled here.

Factors associated with unmet need for support to maintain independence in later life: a systematic review of quantitative and qualitative evidence.

BACKGROUND: populations are considered to have an 'unmet need' when they could benefit from, but do not get, the necessary support. Policy efforts to achieve equitable access to long-term care require an understanding of patterns of unmet need. A systematic review was conducted to identify factors associated with unmet need for support to maintain independence in later life. METHODS: seven bibliographic databases and four non-bibliographic evidence sources were searched. Quantitative observational studies and qualitative systematic reviews were included if they reported factors associated with unmet need for support to maintain independence in populations aged 50+, in high-income countries. No limits to publication date were imposed. Studies were quality assessed and a narrative synthesis used, supported by forest plots to visualise data. FINDINGS: forty-three quantitative studies and 10 qualitative systematic reviews were included. Evidence across multiple studies suggests that being male, younger age, living alone, having lower levels of income, poor self-rated health, more functional limitations and greater severity of depression were linked to unmet need. Other factors that were reported in single studies were also identified. In the qualitative reviews, care eligibility criteria, the quality, adequacy and absence of care, and cultural and language barriers were implicated in unmet need. CONCLUSIONS: this review identifies which groups of older people may be most at risk of not accessing the support they need to maintain independence. Ongoing monitoring of unmet need is critical to support policy efforts to achieve equal ageing and equitable access to care.

Bacteriophage-Based Detection of Staphylococcus aureus in Human Serum.

Bacteriophages have been investigated for clinical utility, both as diagnostic tools and as therapeutic interventions. In order to be applied successfully, a detailed understanding of the influence of the human matrix on the interaction between bacteriophage and the host bacterium is required. In this study, a cocktail of luciferase bacteriophage reporters was assessed for functionality in a matrix containing human serum and spiked with Staphylococcus aureus. The inhibition of signal and loss of sensitivity was evident with minimal amounts of serum. This phenotype was independent of bacterial growth and bacteriophage viability. Serum-mediated loss of signal was common, albeit not universal, among S. aureus strains. Immunoglobulin G was identified as an inhibitory component and partial inhibition was observed with both the f(ab')2 and Fc region. A modified bacteriophage cocktail containing recombinant protein A was developed, which substantially improved signal without the need for additional sample purification. This study highlights the importance of assessing bacteriophage activity in relevant host matrices. Furthermore, it identifies an effective solution, recombinant protein A, for promoting bacteriophage-based detection of S. aureus in matrices containing human serum.