Risultati per: Gestione dei sintomi del tratto urinario inferiore femminili (LUTS - Lower Urinary Tract Symptoms)

Background
The KEYNOTE-966 study demonstrated that pembrolizumab combined with chemotherapy is more effective than chemotherapy alone as first-line treatment for patients with advanced biliary tract cancer (BTC). However, the cost-effectiveness of pembrolizumab combined with chemotherapy in the USA and China remains uncertain.

Objective
This study aimed to evaluate the cost-effectiveness of pembrolizumab plus chemotherapy compared with placebo plus chemotherapy from the perspective of US and Chinese payers.

Design
Markov models with three health states were developed to simulate the process of advanced BTC. Cost data were obtained from available databases and published literature in the US scenario, and from local institutions from the China scenario. Utility values were derived from previous studies.

Outcome measures
Primary outcomes included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs).

Results
In the US scenario, pembrolizumab plus chemotherapy increased costs by US$97,222.13, compared with chemotherapy alone, with a gain of 0.12 QALYs, resulting in an ICER of US$810 184.42 per QALY. In the China scenario, the ICER was $360 933.50 per QALY. Sensitivity analyses indicated the costs of pembrolizumab had the greatest impact on the model in both scenarios. Further analyses suggested that the optimal price of pembrolizumab in the USA would be nearly US$10.33 /mg, while a price reduction of over 90% would be required for the combined therapy to be cost-effective for patients in China.

Conclusion
Based on the willingness-to-pay threshold set at three times the gross domestic product per capita, pembrolizumab plus chemotherapy is not a cost-effective option for patients with advanced BTC in either the USA or China. Significant price reduction for pembrolizumab may be necessary to achieve an acceptable ICER.

Trial registration number
NCT04003636; postresults.

Individuals with type 2 diabetes (T2D) face an elevated risk of chronic obstructive pulmonary disease (COPD), and although research suggests glucose-lowering medications may help manage COPD exacerbations, the association is unclear.

Introduction
Increasing awareness of the high frequency, wide spectrum and disabling nature of symptoms that can persist following COVID-19 infection has prompted the investigation of management strategies. Our study aims to determine the effectiveness of atorvastatin on cognitive function, physical activity, mood, health-related quality of life and features of neurovascular impairment and neuroinflammation in adults with ongoing neurological symptoms after COVID-19 infection.

Methods and analysis
The STatin TReatment for COVID-19 to Optimise NeuroloGical recovERy study is an ongoing international, investigator-initiated and conducted, multicentre, prospective, randomised, open label, blinded endpoint trial with fixed time points for outcome assessments. A total of 410 participants with long covid neurological symptoms were planned to be randomly assigned to either the intervention group to receive 40 mg atorvastatin for 12 months or to a control group of no treatment, on top of usual care.

Ethics and dissemination
This study protocol was designed, implemented and reported, in accordance with the International Conference on Harmonisation guidelines for Good Clinical Practice, the National Health and Medical Research Council of Australia, the National Statement on Ethical Conduct in Human Research and with the ethical principles laid down in the World Medical Association Declaration of Helsinki. Central ethics committee approval was obtained from Sydney Local Health District Royal Prince Alfred Hospital Ethics (No: X21-0113 and 2021/ETH00777 10) in Australia. Site-specific ethics committee approvals were obtained elsewhere before any local study activities. All participants provided written informed consent.

Trial registration number
The study protocol is registered at Clinicaltrials.gov (NCT04904536).

I delegati si riuniranno martedì a Ginevra per perfezionare il testo e dare la loro approvazione definitiva

Objective
This study aimed to explore the predictive value of severe burnout complaints, symptom dimension of burnout and depressive symptoms for subsequent all-cause medically certified sickness absence (ACMCSA) during the pandemic among physicians in Sweden.

Design
A 1 year follow-up panel cohort observational study—the Longitudinal Occupational Health Survey for HealthCare in Sweden. At baseline (February–May 2021), a representative sample of 6699 physicians was drawn from the Swedish occupational register and invited to participate in the study. At follow-up (March–May 2022), the full sample (excluding those who died, retired, stopped working as a physician or migrated, n=94) was invited to answer the survey.

Setting
Swedish primary and specialist healthcare.

Participants
At baseline, the response rate was 41.3% (n=2761) of which 1575 also answered at follow-up.

Primary and secondary outcome measures
ACMCSA data came from the Swedish Social Insurance Agency. The Burnout Assessment Tool (BAT-23) was used to measure burnout, including a burnout total score and scores for the four symptom dimensions of exhaustion, mental distance, emotional impairment and cognitive impairment. Depressive symptoms were assessed using the Symptom Checklist-core depression (SCL-CD6). Associations between baseline burnout and depressive symptoms and subsequent ACMCSA were estimated with logistic regression analyses.

Results
ACMCSA was found in 9% of the participating physicians. In the sample, 4.7% had severe burnout complaints, and 3.7% had depressive symptoms. Burnout (OR=2.57; 95% CI=1.27 to 5.23) and the burnout symptom dimensions emotional impairment (OR=1.80; 95% CI=1.03 to 3.15) and cognitive impairment (OR=2.52; 95% CI=1.12 to 5.50) were associated with a higher likelihood of subsequent ACMCSA. Depressive symptoms were not associated with ACMCSA when adjusted for severe burnout complaints and other covariates.

Conclusion
This study demonstrates the distinction between burnout and depressive symptoms, particularly in predicting future ACMCSA. Early intervention targeting exhaustion and burnout may mitigate symptom development and reduce the risk of ACMCSA.

Stroke, Ahead of Print. BACKGROUND:Urinary incontinence after a stroke significantly affects patient outcomes and quality of life. It is commonly associated with uninhibited detrusor contractions, but the underlying neural mechanisms remain poorly understood. This study aimed to explore the brain activity patterns associated with volitional and involuntary bladder contractions in stroke survivors.METHODS:This cohort study enrolled 15 stroke survivors with documented urinary incontinence and 9 healthy controls. Participants underwent simultaneous blood oxygen level–dependent functional magnetic resonance imaging of the brain and urodynamics, capturing 25 involuntary and 23 volitional bladder emptying events in patients with stroke and 35 volitional voiding events in healthy individuals. We used general linear modeling in functional magnetic resonance imaging analysis to discern neural activity patterns during these events and in the phases leading up to them, aiming to identify neural mechanisms underlying involuntary versus volitional urinary control. Statistical significance for neuroimaging analyses was set atP

Background
Respiratory viral infections (RVIs) are a significant cause of morbidity and hospital admission worldwide. However, the management of most viral infection-associated diseases remains primarily supportive. The recent COVID-19 pandemic has underscored the urgent need for a deeper understanding of RVIs to improve patient outcomes and develop effective treatment strategies. The Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal Study is an observational study which addresses this need by investigating the heterogeneity of RVIs in hospitalised adults, aiming to identify clinical and biological predictors of adverse outcomes. This study aims to bridge critical knowledge gaps in the clinical course and the economic impact of RVIs by characterising the phenotypic diversity of these infections and their recovery patterns following hospital admission and thus assisting with the optimal design of future interventional studies.

Methods and analysis
This prospective longitudinal observational study (V.6, 20 September 2023) will be conducted across multiple UK secondary care sites from August 2022 onwards, with an aim to enrol 1000 participants testing positive for RVI. Adults admitted with respiratory symptoms who test positive for RVIs via the BioFire® FilmArray® System or other validated diagnostic PCR tests will be enrolled. The data collected include patient demographics, clinical history, comorbidities and symptoms experienced prior to, during and after hospitalisation with follow-up after discharge at weeks 1, 2, 4, 8, 12 and 26. In addition, biological samples are collected at multiple time points during the hospital stay. The primary endpoints are to study the impact of different RVIs and identify predictors of disease progression and length of stay. Secondary endpoints include time to recovery and healthcare cost. Exploratory endpoints focus on biomarker profiles associated with virus type and clinical outcomes.

Ethics and dissemination
The study protocol received ethical approval from the relevant committees (English Ethics Reference Number: 22/WM/0119; Scottish Ethics Reference Number: 22-SS-0101, 20/09/2023). For patients who lack the capacity to consent, the study complies with the Mental Capacity Act 2005, using a consultee process where a family member, carer or an independent clinician may provide assent on behalf of the patient. Data from all the study centres will be analysed together and disseminated through peer-reviewed journals, conference presentations and workshops. The study group will ensure that participants and their families are informed of the study findings promptly and in an accessible format.

Trial registration number
ISRCTN49183956.

Introduction
Complexity leads to some dystonias being considered as rare diseases with scarce synthesised evidence. Despite the deficit of scientific evidence, deep brain stimulation (DBS) is currently an effective treatment for dystonias using different brain targets, providing significant improvement of dystonic symptoms regardless of their cause. However, there is considerable variability and non-response rate due to factors such as classification, semiology, duration, aetiology and genetic cause of the disease. This protocol presents the methodology of a planned systematic review to assess the efficacy of DBS as a treatment for monogenic dystonia symptoms, a broad spectrum of pathogenic dystonias due to variants in single genes not yet explored.

Methods and analysis
This protocol follows the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols guidelines. With the aim to test the efficacy of DBS in monogenic dystonias, the research question in population, intervention, comparator and outcomes format will cover patients with monogenic dystonia treated with DBS with a minimum of 3 months’ follow-up after surgery. The outcomes will be assessed using generic and specific scales to measure the efficacy and safety of the intervention. The search will be performed in generic and specific databases and bibliographic resources from 2000. We will include systematic reviews, randomised controlled trials and primary studies in English. In this protocol, the initial search strategy in MEDLINE is presented. Additionally, the protocol provides a description of the prospective assessment of the risk of bias in the selected studies. If studies appear homogeneous and the sample of patients is sufficiently large, a meta-analysis and a subgroup analysis are planned.

Ethics and dissemination
Ethics committee approval is not required. The results of the review will be published through an open access journal.

PROSPERO registration number

CRD42023448145

Background
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising effects on liver histology in phase 2 trials enrolling patients with metabolic dysfunction-associated steatotic liver disease. However, the impact of GLP-1RAs on the long-term risk of major adverse liver-related outcomes (MALOs) remains uncertain.

Objective
We performed a meta-analysis of observational cohort studies to quantify the magnitude and direction of the association between GLP-1RA use and MALOs in people with type 2 diabetes (T2D).

Design
We systematically searched eligible cohort studies comparing GLP-1RA new users versus users of other glucose-lowering medications. The primary outcome was the cumulative incidence rates of MALOs. Secondary outcomes included hepatic decompensation events, hepatocellular carcinoma (HCC) and liver-related mortality. Random-effects models were used to calculate incidence rate ratios (IRRs).

Results
11 retrospective cohort studies with aggregate data on 1 467 220 patients with T2D (647 903 GLP-1RA new users, 819 317 non-users) were included. GLP-1RA use was significantly associated with a lower risk of MALOs (IRR 0.71, 95% CI 0.57 to 0.88) and hepatic decompensation (IRR 0.70, 95% CI 0.52 to 0.94). Association with reduced risk of HCC was also observed (IRR 0.82, 95% CI 0.61 to 1.11). Compared with other antidiabetic medications, GLP-1RAs showed superior effectiveness versus SGLT2 inhibitors in preventing MALOs (IRR 0.93, 95% CI 0.87 to 0.99), versus DPP-4 inhibitors in preventing hepatic decompensation (IRR 0.74, 95% CI 0.66 to 0.83) and versus insulin therapy in preventing HCC (IRR 0.32, 95% CI 0.13 to 0.80).

Conclusions
GLP-1RA use is associated with a lower risk of liver-related complications and hepatic decompensation in people with T2D. These findings suggest a role of GLP-1RAs in preventing liver-related complications beyond their beneficial cardiometabolic effects.

Circulation, Volume 151, Issue 14, Page e918-e918, April 8, 2025.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Objective
Our study explored the association between depressive symptoms and non-fatal cardiovascular disease, as well as other significant risk factors for non-fatal cardiovascular disease, in middle-aged and elderly patients with hypertension in China.

Design
Prospective cohort study.

Setting
Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) database over a 9-year period (2011–2020).

Participants
Middle-aged and elderly patients with hypertension aged 45 and above in China.

Outcome measures
Non-fatal cardiovascular disease was ascertained based on self-reported, physician-diagnosed heart disease. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale-10.

Results
A total of 1755 participants were enrolled in the prospective cohort study. The incidence of non-fatal cardiovascular diseases among patients with hypertension was 5 per 1000 person-months. There was a positive linear correlation between depressive symptoms and the risk of non-fatal cardiovascular diseases (pnon-linear=0.625). Meanwhile, an inverted U-shaped relationship was identified between baseline duration of hypertension and risk of non-fatal cardiovascular diseases; those experiencing hypertension for 15 years had the highest risk, with the risk decreasing for durations above or below this value (pnon-linear

In a phase 2 manufacturer-funded trial, lepodisiran safely reduced Lp(a) levels in a dose-dependent manner.