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.).

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.

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.

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.

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).

Identifying older adults with frailty approaching end-of-life: A systematic review.

BACKGROUND: People with frailty may have specific needs for end-of-life care, but there is no consensus on how to identify these people in a timely way, or whether they will benefit from intervention. AIM: To synthesise evidence on identification of older people with frailty approaching end-of-life, and whether associated intervention improves outcomes. DESIGN: Systematic review (PROSPERO: CRD42020462624). DATA SOURCES: Six databases were searched, with no date restrictions, for articles reporting prognostic or intervention studies. Key inclusion criteria were adults aged 65 and over, identified as frail via an established measure. End-of-life was defined as the final 12 months. Key exclusion criteria were proxy definitions of frailty, or studies involving people with cancer, even if also frail. RESULTS: Three articles met the inclusion criteria. Strongest evidence came from one study in English primary care, which showed distinct trajectories in electronic Frailty Index scores in the last 12 months of life, associated with increased risk of death. We found no studies evaluating established clinical tools (e.g. Gold Standards Framework) with existing frail populations. We found no intervention studies; the literature on advance care planning with people with frailty has relied on proxy definitions of frailty. CONCLUSION: Clear implications for policy and practice are hindered by the lack of studies using an established approach to assessing frailty. Future end-of-life research needs to use explicit approaches to the measurement and reporting of frailty, and address the evidence gap on interventions. A focus on models of care that incorporate a palliative approach is essential.

Exploring the impacts of the 2012 Health and Social Care Act reforms to commissioning on clinical activity in the English NHS: a mixed methods study of cervical screening.

OBJECTIVES: Explore the impact of changes to commissioning introduced in England by the Health and Social Care Act 2012 (HSCA) on cervical screening activity in areas identified empirically as particularly affected organisationally by the reforms. METHODS: Qualitative followed by quantitative methods. Qualitative: semi-structured interviews (with NHS commissioners, managers, clinicians, senior administrative staff from Clinical Commissioning Groups (CCGs), local authorities, service providers), observations of commissioning meetings in two metropolitan areas of England. Quantitative: triple-difference analysis of national administrative data. Variability in the expected effects of HSCA on commissioning was measured by comparing CCGs working with one local authority with CCGs working with multiple local authorities. To control for unmeasured confounders, differential changes over time in cervical screening rates (among women, 25-64 years) between CCGs more and less likely to have been affected by HSCA commissioning organisational change were compared with another outcome-unassisted birth rates-largely unaffected by HSCA changes. RESULTS: Interviewees identified that cervical screening commissioning and provision was more complex and 'fragmented', with responsibilities less certain, following the HSCA. Interviewees predicted this would reduce cervical screening rates in some areas more than others. Quantitative findings supported these predictions. Areas where CCGs dealt with multiple local authorities experienced a larger decline in cervical screening rates (1.4%) than those dealing with one local authority (1.0%). Over the same period, unassisted deliveries decreased by 1.6% and 2.0%, respectively, in the two groups. CONCLUSIONS: Arrangements for commissioning and delivering cervical screening were disrupted and made more complex by the HSCA. Areas most affected saw a greater decline in screening rates than others. The fact that this was identified qualitatively and then confirmed quantitatively strengthens this finding. The study suggests large-scale health system reforms may have unintended consequences, and that complex commissioning arrangements may be problematic.

Beyond the parish pump: what next for public health?

BACKGROUND: Public health has had a history characterised by uncertainty of purpose, locus of control, and workforce identity. In many health systems, the public health function is fragmented, isolated and under-resourced. We use the most recent major reforms to the English National Health Service and local government, the Health and Social Care Act 2012 (HSCA12), as a lens through which to explore the changing nature of public health professionalism. METHODS: This paper is based upon a 3-year longitudinal study into the impacts of the HSCA12 upon the commissioning system in England, in which we conducted 141 interviews with 118 commissioners and senior staff from a variety of health service commissioner and provider organisations, local government, and the third sector. For the present paper, we developed a subset of data relevant to public health, and analysed it using a framework derived from the literature on public health professionalism, exploring themes identified from relevant policy documents and research. RESULTS: The move of public health responsibilities into local government introduced an element of politicisation which challenged public health professional autonomy. There were mixed feelings about the status of public health as a specialist profession. The creation of a national public health organisation helped raise the profile of profession, but there were concerns about clarity of responsibilities, accountability, and upholding 'pure' public health professional values. There was confusion about the remit of other organisations in relation to public health. CONCLUSIONS: Where public health professionals sit in a health system in absolute terms is less important than their ability to develop relationships, negotiate their roles, and provide expert public health influence across that system. A conflation between 'population health' and 'public health' fosters unrealistic expectations of the profession. Public health may be best placed to provide leadership for other stakeholders and professional groups working towards improving health outcomes of their defined populations, but there remains a need to clarify the role(s) that public health as a specialist profession has to play in helping to fulfil population health goals.

A relevant in vitro human model for the study of Zika virus antibody-dependent enhancement.

Zika virus (ZIKV) is a mosquito-borne flavivirus that has recently been responsible for a serious outbreak of disease in South and Central America. Infection with ZIKV has been associated with severe neurological symptoms and the development of microcephaly in unborn fetuses. Many of the regions involved in the current outbreak are known to be endemic for another flavivirus, dengue virus (DENV), which indicates that a large percentage of the population may have pre-existing DENV immunity. Thus, it is vital to investigate what impact pre-existing DENV immunity has on ZIKV infection. Here, we use primary human myeloid cells as a model for ZIKV enhancement in the presence of DENV antibodies. We show that sera containing DENV antibodies from individuals living in a DENV-endemic area are able to enhance ZIKV infection in a human macrophage-derived cell line and primary human macrophages. We also demonstrate altered pro-inflammatory cytokine production in macrophages with enhanced ZIKV infection. Our study indicates an important role for pre-existing DENV immunity on ZIKV infection in primary human immune cells and establishes a relevant in vitro model to study ZIKV antibody-dependent enhancement.

Garlic Organosulfur Compounds Reduce Inflammation and Oxidative Stress during Dengue Virus Infection.

Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant global human disease and mortality. One approach to develop treatments for DENV infection and the prevention of severe disease is through investigation of natural medicines. Inflammation plays both beneficial and harmful roles during DENV infection. Studies have proposed that the oxidative stress response may be one mechanism responsible for triggering inflammation during DENV infection. Thus, blocking the oxidative stress response could reduce inflammation and the development of severe disease. Garlic has been shown to both reduce inflammation and affect the oxidative stress response. Here, we show that the garlic active compounds diallyl disulfide (DADS), diallyl sulfide (DAS) and alliin reduced inflammation during DENV infection and show that this reduction is due to the effects on the oxidative stress response. These results suggest that garlic could be used as an alternative treatment for DENV infection and for the prevention of severe disease development.

Screening and detection of human papillomavirus (HPV) high-risk strains HPV16 and HPV18 in saliva samples from subjects under 18 years old in Nevada: a pilot study.

BACKGROUND: Human papillomaviruses (HPV) are oncogenic and mainly associated with cervical cancers. Recent evidence has demonstrated HPV infection in other tissues, including oral epithelia and mucosa. Although a recent pilot study provided new information about oral HPV status in healthy adults from Nevada, no information was obtained about oral HPV prevalence among children or teenagers, therefore, the goal of this study is to provide more detailed information about oral prevalence of high-risk HPV among children and teenagers in Nevada. METHODS: This retrospective study utilized previously collected saliva samples, obtained from pediatric dental clinic patients (aged 2 - 11) and local school district teenagers (aged 12-17) for high-risk HPV screening (n=118) using qPCR for quantification and confirmation of analytical sensitivity and specificity. RESULTS: A small subset of saliva samples were found to harbor high-risk HPV16 (n=2) and HPV18 (n=1), representing a 2.5% of the total. All three were obtained from teenage males, and two of these three samples were from White participants. CONCLUSIONS: Although this retrospective study could not provide correlations with behavioral or socioeconomic data, this project successfully screened more than one hundred saliva samples for high-risk HPV, confirming both HPV16 and HPV18 strains were present in a small subset. With increasing evidence of oral HPV infection in children, this study provides critical information of significant value to other dental, medical, oral and public health professionals who seek to further an understanding of oral health and disease risk in pediatric populations.