Risultati per: Passo 12. Ripulire in modo mirato le cartelle cliniche degli assisiti

Annals of Internal Medicine, Ahead of Print.

Objectives
Telehealth may offer a cost-effective, accessible and convenient healthcare service model; however, the acceptability, safety and perceptions of telehealth delivered lifestyle interventions in those with non-alcoholic fatty liver disease (NAFLD) is unknown.

Design
This was a mixed-methods evaluation of a telehealth delivered 12-week exercise, dietary support and behavioural change programme (Tele-ProEx).

Setting and participants
12 adults receiving the intervention (47–77 years) with NAFLD living in Australia.

Outcome measures
Participants were assessed postintervention via questionnaires to evaluate acceptability and satisfaction with the programme, usability (exercise app) and perceptions of safety. Semistructured interviews were also conducted, and qualitative thematic analysis was used to identify themes.

Results
Participants reported moderate to high acceptability (overall mean±SD scores out of 5: exercise programme 3.9±0.5; dietary support to increase plant protein intake 4.0±0.7; behavioural modification 3.6±0.4). Satisfaction was high (overall mean score 3.7±0.3 out of 4), the programme was perceived as safe (overall mean score, 4.4±0.5 out of 5) and app usability was above average (mean score 75.6±5.2 out of 100). Thematic analysis revealed participants perceived telehealth as being comparable to face-to-face interactions with health professionals. Common exercise barriers were alleviated by the personalised programme, while participants with low previous exposure to plant protein foods found the dietary recommendations challenging. Social support and engagement were deemed important for supporting motivation and adherence.

Conclusions
In adults with NAFLD, a telehealth delivered multifaceted lifestyle programme was well accepted and perceived as safe, indicating telehealth offers a viable delivery model in this population. Key features important to participants were the personalised and flexible approach utilising engaging delivery methods that featured social support.

Trial registration number
ACTRN12621001706864.

Stroke, Ahead of Print. Neuroinflammation significantly contributes to stroke pathophysiology, leading to tissue damage and neurological deficits. Baicalein, a potent 12/15-LOX (12/15-lipoxygenase) inhibitor, demonstrates neuroprotective effects by reducing inflammatory lipid mediators, modulating key inflammatory pathways, and attenuating oxidative stress. Experimental studies indicate that baicalein can diminish infarct size and neurological deficits while improving safety and tolerability. Combination therapies with baicalein show promise in enhancing stroke outcomes. Overall, targeting 12/15-LOX and employing baicalein represents a promising approach to modulating neuroinflammation and improving recovery in stroke patients. This review highlights the therapeutic potential of inhibiting the 12/15-LOX pathway and utilizing the natural compound baicalein to mitigate poststroke neuroinflammation.

A causa delle infezioni da antibioticoresistenza occupati quasi 3 milioni di posti letto nel Paese

Per mutazioni genetiche ‘prevenzione e medicina di precisione’

Objectives
To conduct a cost-utility analysis of an implementation package that has been developed aiming to embed the referral of people with type 2 diabetes mellitus (T2DM) to structured self-management education (SSME) from primary care into routine practice compared with usual care.

Design
Model-based cost-effectiveness analysis using the School for Public Health Research type 2 diabetes treatment model. With costs and effectiveness parameters coming from analyses of data from a cluster randomised control trial.

Setting
English National Health Service.

Participants
People with T2DM from 64 GP practices in England.

Interventions
Embedding SSME implementation package Usual care.

Primary and secondary outcome measures
The primary outcome measure was the incremental cost-effectiveness ratio. Secondary outcome measures included the probability of Embedding implementation package being cost-effective and value of information.

Results
The estimated cost of the intervention was £40 316 across the study sites, which equates to £0.521 per patient across all practices. For the base case, the estimated mean discounted incremental lifetime cost of the intervention per patient is £48.19. This is associated with a mean per patient incremental quality-adjusted life-year (QALY) estimate of 0.006, producing an incremental cost-effectiveness ratio of £8311 per QALY gained. This has a 73.1% probability of the intervention being cost-effective at a funding threshold of £20 000 per QALY gained. Scenario analyses indicate that alternative parameterisations can lead to this finding being overturned.

Conclusions
The effectiveness of the Embedding packages was hampered by the COVID-19 pandemic. However, our base case analysis shows that Embedding could be cost-effective for this patient population, but this was subject to significant structural uncertainty. This suggests that while implementation initiatives can be highly cost-effective in this population, more robust evidence or further incentivisation will be required before widespread adoption can be recommended.

Trial registration number
ISRCTN23474120, registered 05/04/2018.

Oncologi,ma meno del 50% cittadini riceve consigli su stili vita

Stroke, Volume 56, Issue Suppl_1, Page A26-A26, February 1, 2025. Introduction:Except for vagal nerve stimulation, no treatment exists to restore function in chronic stroke patients. Several prior intracerebral stem cell trials were promising, but are not being further developed.Objective:NR1 is a human embryonic derived neural stem cell that improved motor-sensory function in rodent stroke models, and was expanded to produce GMP cryopreserved cell lots. The safety&efficacy of NR1 intracerebral transplantation in chronic stroke patients was assessed over 12 months.Methods:Inclusion Criteria: 18-75 yo; 6-60 mos post-ischemic subcortical MCA stroke; mRS 3-4. Subjects were transplanted with 2.5M, 5M, 10M or 20M. Primary Outcomes: Adverse events 0-12 mos; Change in total Fugl-Meyer motor score (FMMS, max 100) compared to baseline at 12 months (≥10 points improvement considered “clinically meaningful”). Other outcomes: UE FMMS, LE FMMS, Gait Speed test, Barthel Index (BI), NIHSS, MR FLAIR, Resting State fMRI and [18F]FDG PET.Results:18 patients were transplanted. Adverse events included headache, worsened baseline expressive aphasia and asymptomatic chronic subdural hygroma, all resolving spontaneously. All 17 pts with f/u ≥3 mos demonstrated improved total FMMS and 11 of these 17 subjects showed clinically meaningful recovery in total FMMS. At 12 mos subjects increased 12.1 (+/- 1.8) points for total FMMS (p=0.00002), 7.4 (+/-1.6) points for UE FMMS (p=0.00057), 4.7 (+/-0.5) points for LE FMMS (p =0.0000009), 7.7 (+/-2.5) points for BI, while NIHSS improved by 1.77 (+/-0.47) and gait speed improved substantially. 14/18 pts demonstrated new transient FLAIR signal in premotor cortex at d7, that resolved by 2 mos, which was highly correlated with sustained neurologic recovery. Resting state fMRI showed improved functional brain connectivity in sensorimotor network, both ipsilesionally&contralesionally. FDG PET showed increased activity in the ipsilesional motor cortex&contralesional cerebellum.Conclusions:Intraparenchymal transplantation of NR1 cells in chronic stroke patients appears safe and well tolerated. Results suggest improved motor function starting at 1 mos and increasing to clinically meaningful recovery in most patients at 12 mos post-implant. UE FMMS improvement surpassed vagal nerve stimulation outcomes.

Stroke, Volume 56, Issue Suppl_1, Page A12-A12, February 1, 2025. Introduction:Animal research suggests that HDL cholesterol (HDL-C) ameliorates reperfusion injury, a phenomenon that worsens clinical outcome following recanalization therapy for ischemic stroke.Hypothesis:We hypothesized that higher HDL-C levels have a guarding effect against cerebral reperfusion injury in human stroke survivors treated with thrombectomy.Methods:We included patients with anterior circulation large vessel occlusion (acLVO) stroke who underwent thrombectomy from 01/2017 to 01/2023 at a tertiary stroke center in Germany into a prospective registry study with retrospective analysis. We assessed the association of HDL-C serum levels and imaging indices of post interventional reperfusion injury (any intracerebral or subarachnoid bleeding involving the ischemic brain region on CT or MRT), functional outcome quantified via modified Rankin scale (mRS) at 90 days and neurological outcome via National Institutes of Health Stroke Scale (NIHSS) score at discharge using multivariable lasso logistic and linear regression adjusted for demographic, clinical and imaging characteristics. We performed sensitivity analysis applying propensity score matching and shift analysis using ordered logistic regression.Results:In our study population of 811 acLVO patients treated with thrombectomy (420 females, median age 77 years [66-84, interquartile range]) reperfusion injury was associated with detrimental functional outcome (adjusted OR 2.87; 95% CI [1.86;4.41]; p=0.000). Higher HDL-C was associated with lower odds of reperfusion injury (adjusted OR 0.57; 95% CI [0.35;0.95]; p=0.03) and emerged as predictor of favorable functional outcome defined as 90-day mRS 0-2 (adjusted OR 0.57; 95% CI [0.34;0.99]; p=0.04) and alleviated neurological deficits with lower NIHSS score at discharge (ß=-2.51; 95CI% [-4.88; -1.30]; p=0.04). On propensity score analysis an HDL-C level exceeding the median (1.15 mmol/L) was associated with a 13.8 % decrease in the probability of reperfusion injury (ß=-0.14; 95CI% [-0.23; -0.05]; p=0.003). A significant shift of 90-day mRS distribution favoring high HDL is shown in the figure.Conclusions:In patients undergoing thrombectomy for acLVO a higher level of HDL-C reduced the odds of reperfusion injury, which translated into improved functional and neurological outcome, hence constituting a possible target of adjunctive neuroprotective treatment.

Stroke, Volume 56, Issue Suppl_1, Page A55-A55, February 1, 2025. Introduction:Approved thrombolytic agents are currently only recommended for acute ischemic stroke (AIS) within 4.5 hours from the last known well (LKW). Hence, there remains an unmet need in the treatment of AIS for safer and more effective thrombolytics, which can also be administered to a broader population with an extended treatment window. JX10 is a novel thrombolytic that works by inducing conformational changes in plasminogen to increase downstream fibrin affinity and promote physiological fibrinolysis instead of direct plasminogen activation like that of tissue plasminogen activators (t-PA). JX10 also exerts anti-inflammatory activity through inhibition of soluble epoxide hydrolase, which may suppress hemorrhagic changes associated with cerebral infarction. In a randomized, double-blind, placebo-controlled, dose-escalation phase 2a study conducted in Japan, JX10 increased vessel recanalization and improved neurologic outcomes. This subgroup analysis evaluated the safety and efficacy of JX10 in participants who presented with acute lacunar infarct.Methods:JX10 or placebo was administered as a single intravenous infusion at a dose of 1, 3, or 6 mg/kg to AIS patients who were ineligible for tissue plasminogen activator or thrombectomy within 12 h of LKW. Safety and Efficacy outcomes were assessed at 90 days.Results:Among the 90 patients enrolled in the trial, a total of 25 patients with acute lacunar infarct were dosed (JX10 1 mg/kg group: 1 subject; 3 mg/kg group: 3 subjects; 6 mg/kg group: 7 subjects; and placebo group: 14 subjects). In the JX10 1, 3, 6 mg/kg, pooled groups, and the placebo group, the rates of mRS 0–1 were 0 subject out of 1 (0.0%), 1 subject out of 3 (33.3%), 3 subjects out of 7 (42.9%), 4 subjects out of 11 (36.4%), and 1 subject out of 14 (7.1%), respectively, and those of mRS 0–2 were 0 subjects out of 1 (0.0%), 3 subjects out of 3 (100.0%), 4 subject out of 7 (57.1%), 7 subjects out of 11 (63.6%), and 2 subjects out of 14 (14.3%), respectively. Despite small numbers, patients with acute lacunar infarct who were treated with JX10 showed trend of improved neurologic function at 90 days, as measured by mRS. Symptomatic intracranial hemorrhage was not observed in any JX10 treated patients.Conclusions:JX10 improved functional outcome in patients who presented with lacunar infarct, as measured by mRS at day 90 vs placebo. Findings support further testing of JX10 in larger and broader patient populations.

Stroke, Volume 56, Issue Suppl_1, Page A51-A51, February 1, 2025. Background:Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, its efficacy on cerebrovascular events is yet to be well established, with conflicting results to date.Objective:We sought to evaluate the efficacy of GLP-1 RAs on stroke risk among its different types in patients with T2DM, heart failure, or obesity.Methods:We performed a systematic literature search on PubMed, EMBASE, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) from inspection until June 30th, 2024, without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model, and a p-value of

Stroke, Volume 56, Issue Suppl_1, Page ADP56-ADP56, February 1, 2025. Introduction:We discovered a marked upregulation of MMP-12 levels in the brain following an ischemic stroke and demonstrated that reducing MMP-12 levels in otherwise healthy rodents decreases brain damage and facilitates functional recovery. This study aimed to assess the effectiveness of MMP-12 gene silencing in improving sensorimotor function recovery in aged mice and hypertensive rats.Methods:Both male and female C57BL/6 mice (≥16 months old) and male spontaneously hypertensive rats (SHRs) (2-3 months old) were subjected to 35-min and 1-h transient right middle cerebral artery occlusion (MCAO), respectively. Appropriate cohorts of animals (25 mice/group; 18 rats/group) received either control shRNA or MMP-12 shRNA plasmids (1 mg/kg) formulated as nanoparticles that were administered intravenously via tail vein 2 h after reperfusion. In mice, stroke symptoms were evaluated using the neurological deficit score at 2-4 hours and 1 day after reperfusion, while the modified neurological severity score was used in rats. Sensorimotor functions were assessed using the sticky tape test, pole test, and rotarod test at baseline (before MCAO) and at regular intervals post-MCAO (days 3, 5, and 7 in mice, and days 1, 3, 5, 7, and 14 in rats).Results:MMP-12 expression in the ischemic brain was significantly increased by 35-min MCAO in aged mice and 1-h MCAO in SHRs, as was previously observed in healthy young mice and rats that were subjected to 1-h and 2-h MCAO, respectively. In comparison to the control shRNA treatment, MMP-12 shRNA treatment facilitated a greater mean recovery of somatosensory function in aged mice (sticky tape latency was significant on day 3 and day 5; sticky tape interaction was significant on day 5) and in SHRs (sticky tape ratio was significant on day 14). Furthermore, MMP-12 shRNA treatment resulted in a greater mean recovery of motor function across all tested time points in aged mice (pole descent score was significant on day 7; rotarod latency was significant on day 7) and in SHRs (rotarod latency was significant on day 5 and day 14).Conclusions:Reducing MMP-12 expression in the ischemic brain facilitates the recovery of both somatosensory and motor function in aged mice and hypertensive rats after transient focal cerebral ischemia. Our findings further reinforce the potential benefits of MMP-12 gene silencing as a therapeutic approach for improving recovery outcomes in stroke patients.

Introduction
Inhalers are critical in asthma treatment, and inappropriate inhaler use leads to poor asthma outcomes. In adults and adolescents, dry powder inhalers (DPIs) are safe and effective alternatives to mainstay pressurised metered dose inhalers and could bridge the asthma care gap while also reducing the environmental burden of asthma care. Despite being licensed for use in ages 5 years old and older, the evidence for clinical effectiveness is less clear for patients between ages 5 and 12 years. This protocol describes a scoping review. The primary aim of the review is to identify and synthesise evidence on the clinical effectiveness of DPI use in children aged 5–12 years old with asthma and other wheezing conditions. The secondary aim of the review is to outline the implementation strategies and outcomes supporting the prescribing or switching to DPIs in children.

Methods and analysis
We will conduct a systematic and comprehensive literature search across four electronic databases (Medline, Embase, Cochrane Library and CINAHL) and grey literature. Screening and data extraction will be done independently by two review authors with discrepancies resolved through consensus. Data will be extracted and charted by two independent reviewers, then presented diagrammatically or tabulated with an accompanying narrative summary.

Ethics and dissemination
Ethical approval was not required for this study as it is a scoping review. The results of this scoping review will be submitted to a peer-reviewed scientific journal for publication.

Introduction
Patients with peripheral artery disease (PAD) can experience intermittent claudication, which limits walking capacity and the ability to undertake daily activities. While exercise therapy is an established way to improve walking capacity in people with PAD, it is not feasible in all patients. Neuromuscular electrical stimulation (NMES) provides a way to passively induce repeated muscle contractions and has been widely used as a therapy for chronic conditions that limit functional capacity. Preliminary trials in patients with PAD demonstrate that stimulation of the leg muscles using a footplate-NMES device can be performed without pain and may lead to significant gains in walking capacity. Studies, to date, have been small and have not been adequately controlled to account for any potential placebo effect. Therefore, the current trial will compare the effect of a 12-week programme of footplate-NMES with a placebo-control on walking capacity (6 min walking distance) and other secondary outcomes in patients with PAD.

Methods and analysis
The Foot-PAD trial is a double-blinded, randomised placebo-controlled trial to determine the effect of a 12-week home-based programme of footplate NMES on walking capacity in people with PAD. This is a single-centre trial with numerous recruitment locations. A total of 180 participants with stable PAD and intermittent claudication will be randomly assigned (1:1 ratio) to receive either footplate-NMES (intervention condition) or footplate-placebo (control condition) for two 30 min periods each day for 12 weeks. The footplate-NMES device will deliver stimulation sufficient to induce contraction of the leg muscles and repeated plantar and dorsiflexion at the ankles. The footplate-placebo device will deliver a momentary low-intensity transient stimulation that is insufficient to induce contraction of the leg muscles. Outcomes will be assessed at baseline (week 0), mid-intervention (week 6), postintervention (week 12) and 6 weeks after the completion of the intervention (week 18). The primary outcome is walking capacity at week 12, measured as maximum walking distance during the 6 min walk test. Secondary outcomes will include pain-free walking distance during the 6 min walk test; pain-free and maximum walking time during a graded treadmill walking test; disease-specific quality of life (Intermittent Claudication Questionnaire), self-reported walking impairment (Walking Impairment Questionnaire) and accelerometer-derived physical activity levels. Exploratory outcomes will include the Ankle-Brachial Index; leg vascular function; perception of device-use experience and symptom monitoring throughout the trial using the Claudication Symptom Instrument and a pain Visual Analogue Scale.

Ethics and dissemination
The Foot-PAD trial has received ethics approval from the Human Research Ethics Committees of Queensland Health Metro North Hospital and Health Service (78962) and the University of the Sunshine Coast (A21659). Regardless of the study outcomes, the study findings will be published in peer-reviewed scientific journals and presented at scientific meetings.

Trial registration number
ACTRN12621001383853.

Studio pubblicato nella rivista Nature Communications

Per alcuni casi di colangiocarcinoma e leucemia mieloide acuta