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1.
Redox Biol ; 77: 103375, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39369582

RESUMEN

BACKGROUND: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have poor 5-year survival. Pharmacological ascorbate (P-AscH-, high dose, intravenous, vitamin C) has shown promise as an adjunct to chemotherapy. We hypothesized adding P-AscH- to gemcitabine and nab-paclitaxel would increase survival in patients with metastatic PDAC. METHODS: Patients diagnosed with stage IV pancreatic cancer randomized 1:1 to gemcitabine and nab-paclitaxel only (SOC, control) or to SOC with concomitant P-AscH-, 75 g three times weekly (ASC, investigational). The primary outcome was overall survival with secondary objectives of determining progression-free survival and adverse event incidence. Quality of life and patient reported outcomes for common oncologic symptoms were captured as an exploratory objective. Thirty-six participants were randomized; of this 34 received their assigned study treatment. All analyses were based on data frozen on December 11, 2023. RESULTS: Intravenous P-AscH- increased serum ascorbate levels from micromolar to millimolar levels. P-AscH- added to the gemcitabine + nab-paclitaxel (ASC) increased overall survival to 16 months compared to 8.3 months with gemcitabine + nab-paclitaxel (SOC) (HR = 0.46; 90 % CI 0.23, 0.92; p = 0.030). Median progression free survival was 6.2 (ASC) vs. 3.9 months (SOC) (HR = 0.43; 90 % CI 0.20, 0.92; p = 0.029). Adding P-AscH- did not negatively impact quality of life or increase the frequency or severity of adverse events. CONCLUSIONS: P-AscH- infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without detriment to quality of life or added toxicity (ClinicalTrials.gov number NCT02905578).

2.
Health Econ ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39238072

RESUMEN

Over the past decade, single mothers have experienced increasing work requirements both in the UK and in other developed countries. Our aim was to examine if increasing job hours are associated with mental health of single mothers compared to partnered mothers. Using 13 waves of the Understanding Society Survey (2009-2023), we estimated the relationship between changing job hours and mental health using difference-in-difference event study design, accounting for differential treatment effects across time and individuals. We also investigated the role of potential mechanisms, including role strain and additional income. Our findings suggest that increasing job hours from part-time to full-time is associated with an instantaneous decrease in mental health of 0.19 standard deviations for single mothers [95% CI: -0.37;-0.01], with no effect for partnered mothers. Further analyses suggest increased role strain for single mothers as a mechanism helping explain these differences. The negative effects of increasing job hours and increased role strain should be considered when developing future welfare policies for single mothers, to ensure that greater work requirements do not undermine the mental health of the already vulnerable population group.

3.
BMC Health Serv Res ; 24(1): 1062, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39272081

RESUMEN

BACKGROUND: One of the key functions and ultimate goals of health systems is to provide financial protection for individuals when using health services. This study sought to evaluate the level of financial protection and its inequality among individuals covered by the Social Security Organization (SSO) health insurance between September and December 2023 in Iran. METHODS: We collected data on 1691 households in five provinces using multistage sampling to examine the prevalence of catastrophic healthcare expenditure (CHE) at four different thresholds (10%, 20%, 30%, and 40%) of the household's capacity to pay (CTP). Additionally, we explored the prevalence of impoverishment due to health costs and assessed socioeconomic-related inequality in OOP payments for healthcare using the concentration index and concentration curve. To measure equity in out-of-pocket (OOP) payments for healthcare, we utilized the Kakwani progressivity index (KPI). Furthermore, we employed multiple logistic regression to identify the main factors contributing to households experiencing CHE. FINDINGS: The study revealed that households in our sample allocated approximately 11% of their budgets to healthcare services. The prevalence of CHE at the thresholds of 10%, 20%, 30%, and 40% was found to be 47.1%, 30.1%, 20.1%, and 15.7%, respectively. Additionally, we observed that about 7.9% of the households experienced impoverishment due to health costs. Multiple logistic regression analysis indicated that the age of the head of the household, place of residence, socioeconomic status, utilization of dental services, utilization of medicine, and province of residence were the main factors influencing CHE. Furthermore, the study demonstrated that while wealthy households spend more money on healthcare, poorer households spend a larger proportion of their total income to healthcare costs. The KPI showed that households with lower total expenditures had higher OOP payments relative to their CTP. CONCLUSION: The study findings underscore the need for targeted interventions to improve financial protection in healthcare and mitigate inequalities among individuals covered by SSO. It is recommended that these interventions prioritize the expansion of coverage for dental services and medication expenses, particularly for lower socioeconomic status household.


Asunto(s)
Composición Familiar , Financiación Personal , Gastos en Salud , Humanos , Irán , Estudios Transversales , Gastos en Salud/estadística & datos numéricos , Masculino , Femenino , Adulto , Financiación Personal/estadística & datos numéricos , Persona de Mediana Edad , Factores Socioeconómicos , Enfermedad Catastrófica/economía , Seguro de Salud/estadística & datos numéricos , Seguro de Salud/economía
4.
Front Endocrinol (Lausanne) ; 15: 1373919, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39301322

RESUMEN

Background: The association between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) has been explored in various studies, revealing inconsistent correlations that impact therapeutic effectiveness. This heterogeneity in findings requires further exploration to understand what may be driving this. Therefore, this study focuses on systematically reviewing the data, classification of variables, and analytical approach to understand if and how this may be contributing to the mixed findings. This review aims to provide insights that can enhance the generalisability of future research findings. Methods: A comprehensive electronic search was conducted, including EMBASE, MEDLINE, PsycINFO, CINAHL, Web of Science Core Collection, Scopus and specialised sleep journals. The included studies were observational studies published in English from 2011 onwards, involving adults above 18 years with OSA and T2DM or prediabetes, and included a control group. Exclusions were pregnant women, interventional studies, randomised trials, systematic reviews, conference abstracts, case studies and studies without a control group or only with descriptive analysis. Results: We reviewed 23 studies that met the inclusion criteria. Among cohort studies, 54% did not report attrition rates, and 52% did not detail methods for handling missing data in all studies. Nine studies (39%) predominantly included male participants. Objective measures were prevalent in assessing OSA, with 11 using home portable sleep monitors and four employing clinic polysomnography, though only three validated home sleep monitors. The apnea-hypopnea index was commonly used to define OSA severity, with six studies adapting the American Academy of Sleep Medicine criteria. Two studies utilised validated self-report questionnaires for OSA symptoms. T2DM diagnosis methods varied, with 17 studies using blood samples, two relying only on self-reporting, and four confirmed diagnosis via medical records. Conclusions: The variability in sample characteristics, data quality, and variable coding may contribute to the mixed finding. This review identifies gaps in using the standardised measures, reporting attrition rates, handling missing data, and including both sexes. Addressing these issues is crucial to enhancing future research generalisability. Standardising diagnostic criteria, considering clinical and sociodemographic factors, and ensuring inclusivity in study populations are essential for advancing understanding and treatment strategies for OSA and T2DM. Protocol registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023397547.


Asunto(s)
Diabetes Mellitus Tipo 2 , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Diabetes Mellitus Tipo 2/complicaciones
5.
Appetite ; 203: 107651, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39216823

RESUMEN

Out-of-home eating (takeaway, take-out and fast-foods) is associated with intakes of higher energy and fat, and lower intakes of micronutrients, and is associated with excess weight gain. In 2017, a unique opportunity arose to measure the association between the opening of a new multi-national fast-food restaurant (McDonald's) and consumption of fast-food on young people aged 11-16. This study uses a repeated cross-sectional design to explore group level change over time with respect to out-of-home eating behaviours of young people. Two secondary schools in Redcar and Cleveland agreed to participate and facilitated the completion of a questionnaire on their pupils eating behaviours at three timepoints a) prior to the new restaurant opening, b) three months post-opening and c) nine months post opening. Reported frequency of visits to McDonald's showed a statistically significant increase in visits between 3 and 9 months of the restaurant opening. This research asks and explores the question of whether the introduction of a new multi-national fast-food restaurant influences eating habits of young people attending schools near the new outlet.

6.
Dementia (London) ; : 14713012241273837, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148243

RESUMEN

Background and Aims: Music-based interventions have been found to benefit people living with dementia and have positive impacts on cognition and well-being. Most people with dementia live in the community and compared to people with dementia in residential care often have less access to music-based interventions. There are many forms of music interventions and singing has shown particular promise; in the realm of music interventions. It is important to determine what aspects of music interventions yield the most benefits for people with dementia. This review aimed to synthesise evidence on the impacts of singing interventions on quality of life, mood and neuropsychiatric symptoms for community-dwelling people with dementia. Methods: We systematically searched three electronic databases (PsycINFO, MEDLINE and Web of Science) for studies reporting on singing interventions with community-dwelling people with dementia. Studies were eligible for inclusion if they reported on a singing intervention with people living with dementia that included an outcome measure of quality of life, mood or agitation. Fourteen publications were identified and included in this review, with a total of n = 361 people with dementia. Results: Despite some inconsistencies across the literature, evidence suggests that singing interventions led to an improvement in mood and a reduction in agitation levels in people living with dementia. There was no strong evidence to suggest that singing interventions led to significant improvements in quality of life. Conclusions: This review highlights the potential of singing interventions as an effective psychosocial intervention for community-dwelling people with dementia. For key developments in this area, we urge that future studies include a control group where possible which will allow for more robust examinations of singing interventions and allow intervention effects to be distinguished from general deterioration in dementia symptoms over time.

7.
Sci Rep ; 14(1): 16453, 2024 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013932

RESUMEN

This study aimed to assess the impact of the COVID-19 pandemic on general practitioner (GP), specialist, and dentist visits among 40 million Iranians covered by the Social Security Organization (SSO). A monthly interrupted time series analysis was conducted over a period of 72 months, including-47 months before the pandemic and 25 months after its onset. The outcomes variables were monthly number of GP, specialist, and dentist visits per 1000 SSO-insured individuals. The analysis was performed by total visits, visits to the SSO direct sector, and visits to the indirect sectors. The study found that in the first month of the pandemic, the number of visits per 1000 insured individuals significantly decreased for visits to GPs (by 51.12, 95% CI -64.42 to -37.88), visits to specialists (by 39.11, 95% CI -51.61 to -26.62), and visits to dentists (by 6.67, 95% CI -8.55 to -4.78). However, during the subsequent months of the pandemic, there was a significant increase in the number of monthly visits for all three categories, with GPs experiencing the highest increase (1.78 visits per 1000 insured), followed by specialists (1.32 visits per 1000 insured), and dentists (0.05 visits per 1000 insured). Furthermore, prior to the pandemic, the number of monthly GP visits per 1000 insured individuals was statistically significantly lower in the indirect sector compared to the direct sector (45.79, 95% CI -52.69 to -38.89). Conversely, the direct sector exhibited lower rates of specialist visits (25.84 visits per 1000 insured individuals, 95% CI 22.87 to 28.82) and dentist visits (0.75 visits per 1000 insured individuals, 95% CI 0.12 to 1.36) compared to the indirect sector. Additionally, the study found that in the first month of the pandemic, the monthly number of GP visits in the indirect sector significantly increased by 34.44 times (95% CI 24.81 to 44.08) compared to the direct sector. For specialist visits and dentist visits, the increase was 3.41 (95% CI -5.87 to 12.69) and 5.01 (95% CI 3.48 to 6.53) per 1000 insured individuals, respectively. Overall, the findings of this study demonstrate statistically significant disruptions in GP, specialist, and dentist visits during the COVID-19 pandemic, although some recovery was observed. Both the direct and indirect sectors experienced decreased visits.


Asunto(s)
COVID-19 , Odontólogos , Humanos , COVID-19/epidemiología , Irán/epidemiología , Odontólogos/estadística & datos numéricos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Pandemias , SARS-CoV-2/aislamiento & purificación , Visita a Consultorio Médico/estadística & datos numéricos , Médicos Generales/estadística & datos numéricos , Análisis de Series de Tiempo Interrumpido , Médicos/estadística & datos numéricos , Adulto Joven , Adolescente , Anciano , Niño
8.
Soc Sci Med ; 353: 117068, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38954859

RESUMEN

Young people's mental health globally has been in decline. Because of their low perceived need, young people's services tend to be the first cut when budgets are reduced. There is a lack of evidence on how a reduction in services and opportunities for young people is associated with their mental health. Additionally, how this may be magnified by place and the assets and challenges of place. The aim of this study is to explore trends in young people's mental health measured by GHQ-12 over time in the twelve regions of the UK. We estimated an interrupted time series model using 2010 as a break point from which there was a shift in government policy to a prolonged period of large reductions in central government funding. Repeated cross-sectional data on young people aged 16-25 is used from the British Household Panel Survey and its successor survey UK Household Longitudinal Survey. Results showed a statistically significant reduction in mental health for young people living in the North East, Wales, and the East of England. The North East was the region with the largest reduction in funding and saw the greatest reduction in young people's mental health. Next, we look at how reductions in local government expenditure related to services for children and young people: children's social services, education, transportation, and culture; explain the observed decline in mental health. We employ a Blinder-Oaxaca Decomposition approach comparing young people's mental health between 2011 and 2017. Results show a marginally statistically significant decrease in young people's mental health over this time. Unobserved factors related to transport spending and children's social services explain some of this gap. Area level factors such as deprivation, infrastructure, and existing assets need to be considered when distributing funding for young people's services to avoid exacerbating regional inequalities in mental health.


Asunto(s)
Gobierno Local , Humanos , Estudios Transversales , Adolescente , Reino Unido , Masculino , Femenino , Estudios Longitudinales , Adulto Joven , Adulto , Salud Mental/estadística & datos numéricos , Servicios de Salud Mental/estadística & datos numéricos , Servicios de Salud Mental/tendencias , Servicios de Salud Mental/economía , Encuestas y Cuestionarios , Disparidades en el Estado de Salud , Financiación Gubernamental/tendencias , Financiación Gubernamental/estadística & datos numéricos , Gastos en Salud/tendencias , Gastos en Salud/estadística & datos numéricos
9.
Autism ; : 13623613241254432, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38757674

RESUMEN

LAY ABSTRACT: Autistic young adults with intellectual disabilities want to be autonomous but are less autonomous than other people. However, they can be autonomous with appropriate support. We wanted to learn how we can support autistic adults with intellectual disabilities to be more autonomous. We designed our study with help from five autistic community partners to make sure the research was relevant to autistic people and would improve their lives. We talked with eight autistic young adults with intellectual disabilities about autonomy. We defined "talk" as verbal language, as well as non-verbal cues such as body language, facial expressions, vocalizations, and laughter. We did art projects and played games while we talked. We met in small groups over multiple sessions. Our participants told us that being autonomous meant being able to be themselves. They told us three main ways to support their autonomy: (1) having choice and control, (2) being able to communicate in their own way, and (3) being in a safe environment. Families, support staff, and caregivers can use this information to help autistic young adults with intellectual disabilities to be autonomous.

10.
J Health Care Poor Underserved ; 35(1): 186-208, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38661866

RESUMEN

OBJECTIVES: This study evaluated how high versus low-intensity community wellness coaching and health behaviors were associated with changes in depression screen results over one year. METHODS: This was an analysis of secondary data collected in a 12-month obesity-related community health worker (CHW) program for 485 Utah women of color. Depression screen (Patient Health Questionnaire-2 score ³3) and self-reported fruit/vegetable consumption and physical activity (FV/PA) were recorded quarterly. Associations between FV/PA and changes in depression screen over time were evaluated in multivariable models. RESULTS: Positive depression screen prevalence declined over 12 months (21.7% to 9.5%) with no difference between study arms. Overall, FV ³5 times/day (AOR=1.5; 95% CI 1.0-2.2), any PA (AOR=3.1; 95% CI 1.5-6.4), and muscle strengthening activities (AOR=1.13; 95% CI 1.01-1.26) were associated with improved depression screen results over time. CONCLUSION: These results indicate value in addressing and evaluating depression in obesity-related interventions in underserved communities.


Asunto(s)
Agentes Comunitarios de Salud , Depresión , Ejercicio Físico , Conductas Relacionadas con la Salud , Obesidad , Humanos , Femenino , Utah/epidemiología , Obesidad/prevención & control , Obesidad/epidemiología , Adulto , Depresión/epidemiología , Depresión/prevención & control , Persona de Mediana Edad , Tutoría , Adulto Joven , Promoción de la Salud/métodos , Promoción de la Salud/organización & administración
11.
Artículo en Inglés | MEDLINE | ID: mdl-38628376

RESUMEN

Significant gaps exist in representation of diverse populations in central-line assessment education and tools. We review some of these gaps and provide some real-world guidance on how to assess central line sites in patients of all skin tones.

12.
Mol Genet Metab ; 142(1): 108349, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38458124

RESUMEN

Metachromatic leukodystrophy (MLD) is a devastating rare neurodegenerative disease. Typically, loss of motor and cognitive skills precedes early death. The disease is characterised by deficient lysosomal arylsulphatase A (ARSA) activity and an accumulation of undegraded sulphatide due to pathogenic variants in the ARSA gene. Atidarsagene autotemcel (arsa-cel), an ex vivo haematopoietic stem cell gene therapy was approved for use in the UK in 2021 to treat early-onset forms of pre- or early-symptomatic MLD. Optimal outcomes require early diagnosis, but in the absence of family history this is difficult to achieve without newborn screening (NBS). A pre-pilot MLD NBS study was conducted as a feasibility study in Manchester UK using a two-tiered screening test algorithm. Pre-established cutoff values (COV) for the first-tier C16:0 sulphatide (C16:0-S) and the second-tier ARSA tests were evaluated. Before the pre-pilot study, initial test validation using non­neonatal diagnostic bloodspots demonstrated ARSA pseudodeficiency status was associated with normal C16:0-S results for age (n = 43) and hence not expected to cause false positive results in this first-tier test. Instability of ARSA in bloodspot required transfer of NBS bloodspots from ambient temperature to -20°C storage within 7-8 days after heel prick, the earliest possible in this UK pre-pilot study. Eleven of 3687 de-identified NBS samples in the pre-pilot were positive for C16:0-S based on the pre-established COV of ≥170 nmol/l or ≥ 1.8 multiples of median (MoM). All 11 samples were subsequently tested negative determined by the ARSA COV of <20% mean of negative controls. However, two of 20 NBS samples from MLD patients would be missed by this C16:0-S COV. A further suspected false negative case that displayed 4% mean ARSA activity by single ARSA analysis for the initial test validation was confirmed by genotyping of this NBS bloodspot, a severe late infantile MLD phenotype was predicted. This led to urgent assessment of this child by authority approval and timely commencement of arsa-cel gene therapy at 11 months old. Secondary C16:0-S analysis of this NBS bloodspot was 150 nmol/l or 1.67 MoM. This was the lowest result reported thus far, a new COV of 1.65 MoM is recommended for future pilot studies. Furthermore, preliminary data of this study showed C16:1-OH sulphatide is more specific for MLD than C16:0-S. In conclusion, this pre-pilot study adds to the international evidence that recommends newborn screening for MLD, making it possible for patients to benefit fully from treatment through early diagnosis.


Asunto(s)
Cerebrósido Sulfatasa , Leucodistrofia Metacromática , Tamizaje Neonatal , Humanos , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/terapia , Leucodistrofia Metacromática/genética , Tamizaje Neonatal/métodos , Recién Nacido , Proyectos Piloto , Cerebrósido Sulfatasa/genética , Femenino , Masculino , Sulfoglicoesfingolípidos , Lactante , Terapia Genética
13.
Mol Genet Metab ; 142(1): 108436, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552449

RESUMEN

Newborn screening (NBS) for metachromatic leukodystrophy (MLD) is based on first-tier measurement of sulfatides in dried blood spots (DBS) followed by second-tier measurement of arylsulfatase A in the same DBS. This approach is very precise with 0-1 false positives per ∼30,000 newborns tested. Recent data reported here shows that the sulfatide molecular species with an α-hydroxyl, 16­carbon, mono-unsaturated fatty acyl group (16:1-OH-sulfatide) is superior to the original biomarker 16:0-sulfatide in reducing the number of first-tier false positives. This result is consistent across 4 MLD NBS centers. By measuring 16:1-OH-sulfatide alone or together with 16:0-sulfatide, the estimated false positive rate is 0.048% and is reduced essentially to zero with second-tier arylsulfatase A activity assay. The false negative rate is predicted to be extremely low based on the demonstration that 40 out of 40 newborn DBS from clinically-confirmed MLD patients are detected with these methods. The work shows that NBS for MLD is extremely precise and ready for deployment. Furthermore, it can be multiplexed with several other inborn errors of metabolism already tested in NBS centers worldwide.


Asunto(s)
Cerebrósido Sulfatasa , Pruebas con Sangre Seca , Leucodistrofia Metacromática , Tamizaje Neonatal , Sulfoglicoesfingolípidos , Humanos , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/sangre , Recién Nacido , Sulfoglicoesfingolípidos/sangre , Tamizaje Neonatal/métodos , Cerebrósido Sulfatasa/sangre , Cerebrósido Sulfatasa/genética , Pruebas con Sangre Seca/métodos , Reacciones Falso Positivas , Biomarcadores/sangre
14.
PLoS Genet ; 20(3): e1011179, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38437227

RESUMEN

Recent human genome-wide association studies have identified common missense variants in MARC1, p.Ala165Thr and p.Met187Lys, associated with lower hepatic fat, reduction in liver enzymes and protection from most causes of cirrhosis. Using an exome-wide association study we recapitulated earlier MARC1 p.Ala165Thr and p.Met187Lys findings in 540,000 individuals from five ancestry groups. We also discovered novel rare putative loss of function variants in MARC1 with a phenotype similar to MARC1 p.Ala165Thr/p.Met187Lys variants. In vitro studies of recombinant human MARC1 protein revealed Ala165Thr substitution causes protein instability and aberrant localization in hepatic cells, suggesting MARC1 inhibition or deletion may lead to hepatoprotection. Following this hypothesis, we generated Marc1 knockout mice and evaluated the effect of Marc1 deletion on liver phenotype. Unexpectedly, our study found that whole-body Marc1 deficiency in mouse is not protective against hepatic triglyceride accumulation, liver inflammation or fibrosis. In attempts to explain the lack of the observed phenotype, we discovered that Marc1 plays only a minor role in mouse liver while its paralogue Marc2 is the main Marc family enzyme in mice. Our findings highlight the major difference in MARC1 physiological function between human and mouse.


Asunto(s)
Estudio de Asociación del Genoma Completo , Oximas , Animales , Humanos , Ratones , Cirrosis Hepática
15.
Artículo en Inglés | MEDLINE | ID: mdl-38340894

RESUMEN

Pediatric neurodegenerative disorders (PNDs), such as juvenile neuronal ceroid lipofuscinosis (CLN3 disease, also called Batten disease) and juvenile Huntington disease, are devastating conditions that result in progressive neurological dysfunction and profound medical comorbidities leading to early mortality in children and young adults.1 There are more than 70 PNDs, with a combined estimated prevalence of ∼0.1 in 1,000 live births.2,3 Individuals with PNDs commonly experience complex neuropsychiatric manifestations such as neurocognitive symptoms (dementia), irritability, aggression and self-injury, mood disorders, sensory alterations, and psychosis. Symptoms are dynamic, changing with illness progression, and evolve over time. Effects on patients and families can be devastating, and caregiver burden is enormous.4 We are a group of colleagues with backgrounds in pediatric neuropsychiatry, pediatric neuropalliative care, and pediatric neurology who care for patients together in specialized clinics.

16.
Clin Cancer Res ; 30(2): 283-293, 2024 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-37773633

RESUMEN

PURPOSE: Pharmacologic ascorbate (P-AscH-) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans. PATIENTS AND METHODS: The single-arm phase II clinical trial (NCT02344355) enrolled 55 subjects, with analysis performed 12 months following the completion of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared across patient subgroups with log-rank tests. Forty-nine of 55 subjects were evaluated using T2*-based MRI to assess its utility as an Fe-dependent biomarker. RESULTS: Median OS was estimated to be 19.6 months [90% confidence interval (CI), 15.7-26.5 months], a statistically significant increase compared with historic control patients (14.6 months). Subjects with initial T2* relaxation < 50 ms were associated with a significant increase in PFS compared with T2*-high subjects (11.2 months vs. 5.7 months, P < 0.05) and a trend toward increased OS (26.5 months vs. 17.5 months). These results were validated in preclinical in vitro and in vivo model systems. CONCLUSIONS: P-AscH- combined with temozolomide and radiotherapy has the potential to significantly enhance GBM survival. T2*-based MRI assessment of tumor iron content is a prognostic biomarker for GBM clinical outcomes. See related commentary by Nabavizadeh and Bagley, p. 255.


Asunto(s)
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Humanos , Antineoplásicos/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Biomarcadores , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/diagnóstico por imagen , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Imagen por Resonancia Magnética , Temozolomida/uso terapéutico
17.
BMJ Case Rep ; 16(12)2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38086577

RESUMEN

Uterine rupture is a rare obstetric emergency that is typically associated with the presence of scar tissue such as in the case of previous caesarean section. In this case report, a primigravid patient presented to the hospital in cardiac arrest with massive haemoperitoneum secondary to a posterior uterine rupture. The histological specimen was found to have diffuse adenomyosis at the site of rupture. On review of the literature, there is insufficient evidence to suggest we as clinicians should alter the antenatal care for patients with known adenomyosis; however, this case highlights how we should have a high index of suspicion for those presenting with signs and symptoms of uterine rupture with known adenomyosis in the absence of other risk factors.


Asunto(s)
Adenomiosis , Rotura Uterina , Femenino , Humanos , Adenomiosis/complicaciones , Factores de Riesgo , Rotura Uterina/etiología , Rotura Uterina/cirugía , Rotura Uterina/diagnóstico , Útero/patología , Embarazo
18.
Lancet Child Adolesc Health ; 7(12): 897-908, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37973254

RESUMEN

Emerging evidence suggests that the higher prevalence of autism in individuals who are assigned male than assigned female at birth results from both biological factors and identification biases. Autistic individuals who are assigned female at birth (AFAB) and those who are gender diverse experience health disparities and clinical inequity, including late or missed diagnosis and inadequate support. In this Viewpoint, an international panel of clinicians, scientists, and community members with lived experiences of autism reviewed the challenges in identifying autism in individuals who are AFAB and proposed clinical and research directions to promote the health, development, and wellbeing of autistic AFAB individuals. The recognition challenges stem from the interplay between cognitive differences and nuanced or different presentations of autism in some AFAB individuals; expectancy, gender-related, and autism-related biases held by clinicians; and social determinants. We recommend that professional development for clinicians be supported by health-care systems, professional societies, and governing bodies to improve equitable access to assessment and earlier identification of autism in AFAB individuals. Autistic AFAB individuals should receive tailored support in education, identity development, health care, and social and professional sense of belonging.


Asunto(s)
Trastorno Autístico , Recién Nacido , Humanos , Masculino , Femenino , Trastorno Autístico/diagnóstico , Trastorno Autístico/epidemiología , Trastorno Autístico/psicología , Identidad de Género , Investigación , Relaciones Interpersonales , Prevalencia
19.
BMJ Open ; 13(11): e076168, 2023 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-37996231

RESUMEN

INTRODUCTION: Psychosocial interventions have been shown to improve mood, relieve stress and improve quality of life for people living with dementia (PwD). To date, most evaluations of singing interventions have focused on the benefits for PwD and not their carers. This research aims to evaluate the benefits of dementia singing groups for both PwD and their carers. METHODS AND ANALYSIS: This 2-year project will observe the impact of two different singing intervention services, one combining singing alongside dance and another that includes a sociable lunch. This project will aim to recruit a total of n=150 PwD and n=150 carers across the two singing interventions. Using a mixed-methods approach, the influence of both services will be analysed via the following outcome measures: quality of life, neuropsychiatric symptoms, social isolation, loneliness, cognition, carer burden and depressive symptoms in PwD and their carers using a prestudy/poststudy design. Regression models will be used to analyse the data with time (pre/post) as the exposure variable. Semistructured interviews will be conducted with a subset of people (n=40) to further investigate the impact of singing services with a specific focus on the acceptability of the interventions, barriers to access and prolonged engagement and potential for remote delivery. Interview data will be analysed using Braun and Clarke's reflexive thematic analysis, and public advisers will assist with coding the transcripts. A social return on investment analysis will be conducted to determine the social impact of the services. ETHICS AND DISSEMINATION: This project has received ethical approval from the University of Liverpool's Ethics Committee (App ref: 12374) and Lancaster University's Ethics Committee (App ref: 3442). All participants will provide informed consent to participate. Results will be presented at national and international conferences, published in scientific journals and publicly disseminated to key stakeholders.


Asunto(s)
Demencia , Canto , Humanos , Cuidadores/psicología , Calidad de Vida , Demencia/terapia , Demencia/psicología , Carga del Cuidador
20.
NIHR Open Res ; 3: 1, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37881458

RESUMEN

Background: Social prescribing (SP) is part of universal personalised care and available to everyone in the UK National Health Service. However, emerging evidence suggests access disparities in social prescribing. This study aimed to investigate the feasibility of using primary care records to access and analyse data on social prescribing. Our secondary aim was to compare characteristics of patients who are offered referral, referred to or decline referral for social prescribing to explore possible inequalities in access to social prescribing. Methods: Patient records (n=3086) were extracted from 11 GP practices across Northwest England for accepted, offered and declined social prescribing referrals. Patient demographics collected included sex, age, ethnicity, mental and physical health diagnoses. Patient characteristics in social prescribing referrals were compared to the overall practice population (practice information from Public Health England). Referral and decline rates were compared by group (e.g. male/female decline rates). Results: GP referral data showed inconsistent recording of wider determinants of health. Patient age, sex and mental and physical health conditions were consistently recorded. Other variables (marital status, interpreter need, education, disability, sexual orientation, non-English language, nationality) were recorded only sporadically and could not be used for analysis. Practices varied in referral patterns. Our preliminary findings identified under-referring of younger age groups and Asians, and higher declined referrals among individuals with physical health diagnoses. Conclusions: Recording discrepancies meant that many patient factors could not be used to identify trends in social prescribing referrals and declines and assess equity. Primary care data recording must be consistent to understand SP referral trends and inequalities relating to the wider determinants of health. Preliminary results suggest some patient groups may be underrepresented in SP referrals, however this requires further investigation.

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