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

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 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 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 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

Objective
Despite the Global Vaccine Action Plan’s goal of at least 90% vaccine coverage for all children, Uganda has made limited progress in vaccination over the past decade. The objective of this study was to examine the subnational trends in the prevalence and inequalities in under-immunisation and zero-dose among children aged 12–23 months in Uganda.

Study design
A retrospective national cross-sectional study.

Setting
Uganda

Participants
Uganda Demographic and Health Survey secondary data of only children aged 12–23 months. The samples selected for analyses were 1507 in 2006, 1409 in 2011 and 2650 children in 2016.

Outcome measure
The primary outcomes were under-immunisation and zero-dose vaccination.
Absolute and relative inequality measures were used in the analysis.

Results
From 2006 to 2016, the under-vaccination rate decreased by 21%, but remained high at 40.8%. The zero-dose vaccination rate dropped by 82%, affecting 1.2% of children in 2016. Subnational inequalities in under-vaccination increased over time with widening gaps between regions. While inequalities across wealth quintiles, maternal education levels and places of residence narrowed, children of mothers with lower education levels continued to have the highest under-vaccination rates. The rural–urban gap for zero-dose vaccination remained unchanged, with rural children disproportionately impacted.

Conclusion
While some progress was made in reducing under-vaccination rates in Uganda within the study period, no region achieved an under-vaccination rate below 20%. This indicates significant challenges in reaching the Sustainable Development Goal target of at least 80% immunisation coverage. Targeted interventions are necessary to improve healthcare access, enhance public health communication and strengthen the health system, particularly in underserved communities and among vulnerable populations.

Studio Gemelli-Cattolica su 35 pazienti in fase avanzata

Introduction
Iron deficiency anaemia (IDA) and dental caries are prevalent diseases among Pakistani children. Limited research has been done to explore their association with permanent teeth. Given the caries susceptibility of permanent first molars and their role in the development of ideal occlusion, this study aimed to estimate caries frequency in these molars and assess its association with IDA in 7–12 year-old children.

Methods and analysis
This analytical cross-sectional study will include 141 children aged 7–12 years visiting physicians in the paediatric OPD of Dr. Ruth K.M. Pfau, Civil Hospital Karachi. Using consecutive sampling, children who met initial screening criteria were further evaluated to determine eligibility for the study. Data collection will involve physical examinations (including weight and height), oral examinations (including the relevant oral hygiene and caries assessments) and laboratory examinations (including the prescribed tests). In addition, questions will be asked about sociodemographic characteristics, history of IDA, oral hygiene habits, smokeless tobacco use and the frequency of cariogenic dietary consumption. Exposure variable will include the presence of IDA, assessed using complete blood count, C-reactive protein and ferritin tests and treated as a dichotomous variable. Outcome variable will include dental caries in at least one permanent first molar, assessed using the Decayed, Missing, and Filled Teeth index and also treated as a dichotomous variable. Analysis will include Poisson regression with robust variance, reporting prevalence ratios with 95% CIs for the association of IDA and dental caries in the permanent first molars. Frequency of children with carious permanent first molars with 95% CIs will also be reported.

Ethics and dissemination
This research has been approved by ethical review committee of Aga Khan University (Reference number: 2024-9692-30593) and the institutional review board of Dow University of Health Sciences (IRB Reference: IRB-3556/DUHS/Approval/2024/196) before participant recruitment. Results will be disseminated through seminars and peer-reviewed publications.