Risultati per: World Alzheimer Report 2015

Worldwide, the rate of deaths from drowning decreased by 38% over the past 2 decades, from 6.1 to 3.8 per 100 000 people. The first-ever status report on drowning prevention from the World Health Organization (WHO) estimated that 300 000 people died from drowning in 2021, down from 375 000 in 2000.

To the Editor In their excellent research, Dr Palmqvist and colleagues report high diagnostic accuracy of blood biomarkers in the diagnosis of Alzheimer disease. The authors used the STROBE checklist for observational studies, but this is a prospective diagnostic accuracy study, for which the STARD checklist is more appropriate.

Objectives
This study aimed to (1) gauge patients understanding and expectations of real-world data and evidence (RWDE) research and (2) use this understanding and patients lived experience to co-create resources and a framework for embedding meaningful patient and public involvement and engagement (PPIE) in RWDE research within the pharmaceutical industry setting.

Setting and participants
An academic organisation, a pharmaceutical company and a PPIE panel of 12 patients or carers partnered to form the project team. The PPIE panel was purposively selected to maximise diversity.

Design
Participatory and co-design methods were used to engender an understanding of the PPIE perspective on RWDE research and the PPIE role within that. Interactive workshops explored understanding and expectations of RWDE research as well as perceived barriers and facilitators of PPIE within each stage of the RWDE research cycle. Workshops were audio and video recorded, with notes captured. Summaries were analysed thematically and shared back with the PPIE panel for validation and further reflection.

Results
We identified a lack of trust and understanding of real-world data, its collection and use and the need to educate the public and researchers. Four themes were identified for meaningful PPIE in RWDE research; equality, diversity and inclusion; feeling valued; ownership and understanding and evaluating impact. We co-created learning resources (video, infographic) and a novel PPIE framework, incorporating potential PPIE activities, resources and support needs for use by researchers conducting RWDE research.

Conclusions
To our knowledge, this is the first project to explore the practicalities of PPIE in RWDE research from the perspective of patients and carers. Some findings confirm PPIE experience and guidance derived from other areas, with some specific insights into the pharmaceutical industry. These underpin the PPIE framework to enable robust and meaningful PPIE in RWDE research. This article includes a plain language summary in the supplement.

‘Ministero continuerà a sostenere la ricerca in questo settore’

Background
Traditionally, intramuscular vitamin B12 injections were considered by patients and clinicians the most effective treatment option for B12 deficiency. The improving understanding of the condition paired with the restricted National Health Service (NHS) resources, resulted in a shift from injections towards tablets. The COVID-19 pandemic accelerated this change, while healthcare services were adapted to reduce COVID-19 transmission. This included new guidelines on vitamin B12 prescribing where injections were substituted by tablets.

Objective
We investigated changes between 2015 and 2024 in prescribing B12 injections and tablets including the effect of the COVID-19 pandemic.

Design, population and setting
This was an observational study of general practice in England covering 100% of the population.

Methods
We used prescribing data published by the NHS Business Service Authority. Monthly prescription counts and rates per 100 000 patients were visualised in longitudinal plots from 1 January 2015 to 30 September 2024. We stratified the analysis by regions in England. Changes in yearly counts and rates were summarised using descriptive statistics. Linear regression and data from before the COVID-19 pandemic were used to model trends from 2020 to 2024 as if the pandemic had not occurred. The predicted values and their 95% CI were used to assess the effect of the pandemic.

Results
The number of prescriptions for B12 formulations doubled in the last 10 years from 2.5 million to 5 million per year. The prescriptions for tablets increased from half a million in 2015 to 2 million in 2024. While the prescriptions for injections increased from 2 million to 3 million. In 2020, there was a sharp drop in prescriptions for injections and a simultaneous rapid increase in prescriptions for tablets coinciding with the onset of the pandemic. There were 806 031 (27%) less than expected prescriptions for injections (2 171 924 observed vs 2 977 956 predicted, 95% CI 2 905 348 to 3 050 565) and 299 834 (27%) more prescriptions for tablets (1 415 315 observed vs 1 115 481 predicted, 95% CI 1 094 350 to 1 136 612). After the 2020 drop, by 2024, injections returned to the prepandemic levels of 3 million prescriptions per year and tablets doubled from 1 million in 2019 to 2 million prescriptions in 2024.

Conclusions
In this study, we document important changes to vitamin B12 prescribing in England over the last 10 years. Before the pandemic, injections were the medication of choice for B12 deficiency but there had been an ongoing debate about the benefits and cost of injections over tablets. The pandemic accelerated the switch from injections to tablets. However, these changes in the pandemic were driven by the availability of resources and not necessarily clinical evidence or patient preference. To establish best practices, more evidence is needed comparing the safety and effectiveness of injections and tablets specific to the condition being treated.

This Viewpoint provides recommendations for health care organizations (HCOs) and clinicians to facilitate the use of artificial intelligence (AI)–enabled systems, including electronic health records with AI features, in routine clinical care and provides pragmatic guidance for HCOs and clinicians at all stages of AI implementation.

This Viewpoint discusses changes needed at local, state, and national levels to improve child health care.

Airalzh Onlus comunica l’apertura di altri due bandi nel 2025

Purpose
To investigate the eligibility for faricimab in a real-world diabetic macular oedema (DMO) population to the YOSEMITE and RHINE trials, and to compare the eligible DMO populations to the trial populations.

Design, settings and participants
This retrospective cross-sectional analysis used data from the Swedish Macula Registry (SMR) between 1 January 2019 and 31 August 2023. Eligibility criteria mirrored the main criteria of the YOSEMITE and RHINE trials: (1) DMO diagnosis, (2) treatment-naïve, (3) 18 years or older, (4) central retinal thickness (CRT) 325 µm or higher and (5) best-corrected visual acuity (BCVA) ranging from 25 to 73 letters. Individuals with registered proliferative diabetic retinopathy (DR) at the start of treatment were excluded. A secondary selection of eligible individuals was conducted using the same criteria, except for BCVA, which ranged from 25 to 77 letters according to national guidelines (treatment practice).

Main outcome measures
Characteristics at the initial visit of the two eligible SMR populations were compared with baseline data from the clinical trials, respectively.

Results
In total, 3777 individuals with DMO were selected from SMR. Of these, 2357 (62.4%) individuals were treatment-naïve, all were 18 years or older, 1928 (51.0%) exhibited CRT≥325 µm, 1175 (31.1%) had 25–73 letters based on phase III studies, while 1528 (40.5%) had 25–77 letters according to treatment practice. After excluding individuals with registered proliferative DR 1171 (31.0%) individuals in the SMR met all criteria based on phase III studies, while 1522 (40.3%) individuals fulfilled the criteria according to treatment practice. The SMR and treatment practice populations were older (YOSEMITE 67.5±11.6 vs 62.8±10.0 years, p

Ministero Salute ha assegnato finanziamento di 1,2 milioni euro

Iniziativa presa dall’Unità operativa di Oncologia del profili

Objective
This study examined real-world treatment patterns and outcomes in patients with melanoma brain metastasis (MBM) treated with first-line immunotherapy consisting of nivolumab plus ipilimumab or anti-programmed death-1 (PD-1) monotherapy (nivolumab or pembrolizumab) or targeted therapy consisting of BRAF/MEK inhibitors.

Design
Retrospective chart review study.

Setting
Academic medical centres, community hospitals and private practice offices.

Participants
Included patients diagnosed with melanoma with brain metastasis in the USA.

Outcome measures
The statistical analysis was descriptive in nature. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared between treatments in a univariate Cox proportional hazards model.

Results
In total, 472 patients with MBM who received first-line nivolumab plus ipilimumab (n=246), anti-PD-1 monotherapy (n=112) or BRAF/MEK inhibitors (n=114) were identified. Patients receiving nivolumab plus ipilimumab, compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors, had favourable baseline prognostic factors, such as younger age, fewer or smaller brain metastases, better Eastern Cooperative Oncology Group performance status and less frequently elevated lactate dehydrogenase. Median follow-up times were 15.4 months (range 0.1 to 37.0), 13.3 months (range 0.3 to 36.6) and 13.9 months (range 1.9 to 36.5), respectively. Numerically longer OS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.47, 95% CI 0.34 to 0.67) or BRAF/MEK inhibitors (HR 0.72, 95% CI 0.50 to 1.04) and numerically longer PFS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.74, 95% CI 0.53 to 1.02) or BRAF/MEK inhibitors (HR 0.82, 95% CI 0.60 to 1.12). With nivolumab plus ipilimumab, anti-PD-1 monotherapy and BRAF/MEK inhibitors, 1-year OS rates were 79%, 60% and 72%, respectively; 1-year PFS rates were 68%, 58% and 59%.

Conclusions
In this real-world study, first-line nivolumab plus ipilimumab appeared to provide benefit versus anti-PD-1 monotherapy and BRAF/MEK inhibitors in patients with MBM, consistent with pivotal trial data. However, the observed benefit may have been due to confounding and selection bias, given that patients receiving nivolumab plus ipilimumab had favourable baseline prognostic factors compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors.

Stroke, Volume 56, Issue Suppl_1, Page ATMP38-ATMP38, February 1, 2025. Background:Randomized clinical trials have demonstrated that IV thrombolysis (IVT) can be administered safely in wake-up stroke (WUS) after MRI- or CT-based imaging selection to improve clinical outcomes. The objective of this study was to evaluate the utilization of IVT to treat WUS using a standardized WUS protocol across a healthcare system.Methods:A WUS protocol using MRI-based imaging selection was implemented across an academic healthcare system with 6 acute care hospitals in the state of Georgia. We prospectively identified all WUS patients who underwent the WUS protocol over a 12 month period through August 15, 2024. Patients were eligible for the WUS protocol if they presented with disabling symptoms identified on awakening, had a CT head without contrast showing no hypodensity to explain clinical symptoms and had CT angiography of the head and neck demonstrating no large vessel occlusion as a cause of symptoms. All patients underwent expedited brain MRI sequences (DWI, T2w FLAIR, GRE) without contrast and IVT was administered at the discretion of the treating neurologist.Results:During the study period, the WUS protocol was activated for 27 patients of which 6 (22%) received IVT (median NIHSS 10, IQR 5-15). Reasons for not receiving IVT included lack of DWI-FLAIR mismatch on MRI (n=11), DWI negative MRI (n=8), IVT declined by patient (n=1) and IVT contraindication (n=1). A modified Rankin scale of 0-1 at 90 days was achieved in 67% of WUS patients treated with IVT and no symptomatic intracerebral hemorrhages. Door-to-needle time within 60 minutes was significantly less likely in WUS compared with non-WUS cases (0% vs 69%, p=0.001). IVT administration in WUS patients made up 2% of all acute ischemic stroke patients receiving IVT.Conclusions:An MRI-based WUS protocol was able to identify a small subset of acute ischemic stroke patients who met eligibility criteria for IVT outside of the 4.5 hour time window. IVT was associated with good clinical outcomes and not associated with any complications.

Stroke, Volume 56, Issue Suppl_1, Page ADP5-ADP5, February 1, 2025. Introduction:Outcomes after thrombolysis with alteplase (tPA) versus tenecteplase (TNK) prior to endovascular thrombectomy (EVT) have not been directly compared in real-world data (RWD). We leveraged systematic analysis for RWD from 2 major academic stroke centers that solely used tPA or TNK prior to EVT over a 4-year period to determine potential differences in recanalization, reperfusion and clinical outcomes.Methods:A retrospective, cohort, multicenter study was conducted to investigate outcomes for patients with large vessel occlusions receiving either tPA+EVT or TNK+EVT. tPA was used exclusively for thrombolysis at one center (n=74), while TNK was used exclusively for thrombolysis at another center (n=130). The primary outcome that was measured was functional independence (defined by a modified Rankin score of 0-1) at discharge. Secondary outcomes that were measured include good functional outcomes (defined by a modified Rankin score of 0-2) at discharge and early neurologic improvement (ENI; defined as an improvement in NIH scores by 8 or more in a 24 hour time period). Safety outcomes included symptomatic intracranial hemorrhage (sICH; defined as a worsening of NIH scores by 4 or more with concurrent PH-2 hemorrhagic transformation in a 24 hour time period), any hemorrhagic transformation (HT), and all-cause mortality by discharge.Results:The rate of functional independence was 25.7% for the tPA+EVT group and 33.8% for the TNK+EVT group (p-value 0.291; RR 1.32 [95% CI 0.55, 3.14]). The rate of good functional outcomes was 35.1% vs 37.7% (p-value 0.831; RR 1.07 [95% CI 0.57, 2.02]). The rate of ENI was 50.0% vs 47.7% (p-value 0.864; RR 0.95 [95% CI 0.63, 1.44]). The rate of sICH was 2.7% vs 0.8% (p-value 0.298; RR 3.51 [95% CI 0.32, 38.1]). The rate of any HT was 32.4% vs 38.4% (p-value 0.45; RR 0.84 [95% CI 0.57, 1.25]). The rate of all cause mortality was 6.8% vs 6.9% (p-value 1.0; RR 0.98 [95% CI 0.34, 2.80]).Conclusions:Real-world evidence on tPA versus TNK prior to EVT reveals potential equivalence in outcomes after acute ischemic stroke. Detailed analyses (site of arterial occlusion, recanalization and reperfusion effectiveness, and transfer times between hospitals) will be conducted to determine if there are practical advantages in utilizing one thrombolytic over another as an adjunct to EVT in patients with large vessel occlusions in real-world practice.

Stroke, Volume 56, Issue Suppl_1, Page ATP393-ATP393, February 1, 2025. Dysregulation of the immune system is a contributing factor in the progression of Alzheimer’s Disease (AD), likely by increased vascular inflammation triggered by brain or peripheral inflammation. Our research has demonstrated that neutrophils play a role in causing hypoperfusion by adhering to and obstructing blood vessels, as seen in both mouse models for and patients with AD. Notably, protein glycosylation of membrane proteins is essential for regulating the adhesion properties of neutrophils to immune cells and the vasculature.Here, we utilize lectin blots to show that sialic acid residues, which are the terminal caps of glycosylation chains, are increased on neutrophil membrane proteins from an amyloidosis Alzheimer’s mouse model. Furthermore, we evaluated the efficacy of the sialyltransferase inhibitor alpha 2,3 sialyltransferase-IN-1 by lectin blot analyses, identifying it to be an effective compound for removing sialic acid from neutrophil membrane proteins. Notably, we performedin vivomultiphoton imaging of cerebral blood flow and capillary stalling in AD mice injected with alpha 2,3 sialyltransferase-IN-1. Our findings demonstrated that reducing sialic acid residues on neutrophils improved cerebral blood flow and capillary stalling.This work suggests that the altered glycosylation pattern, specifically aberrant sialylation residues of neutrophil glycoproteins, are a significant contributing factor to the hypoperfusion observed in AD mouse models and patients. Modulating the glycosylation profile may present a potential therapeutic approach for improving the vascular dysfunction associated with AD pathogenesis.