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The plasma protein binding (PPB) of a drug plays a key role in both its pharmacokinetic and pharmacodynamic properties. During lead optimisation, medium and high throughput methods for the early determination of PPB can provide important information about potential PKPD profile within a chemotype or between different chemotype series. Diffusion ordered spectroscopy (DOSY) is an NMR spectroscopic technique that measures the diffusion of a molecule through the magnetic field gradient, according to its molecular size/weight. Here, we describe the use of DOSY for a rapid and straightforward method to evaluate the PPB of drug molecules, using their binding to bovine serum albumin (BSA) as a model.
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There has been little change to the standard treatment for osteosarcoma (OS) over the last 25 years and there is an unmet need to identify new biomarkers and novel therapeutic approaches if outcomes are to improve. Furthermore, there is limited evidence on the impact of OS treatment on patient-reported outcomes (PROs). ICONIC (Improving Outcomes through Collaboration in Osteosarcoma; NCT04132895) is a prospective observational cohort study recruiting newly diagnosed OS patients across the United Kingdom (UK) with matched longitudinal collection of clinical, biological, and PRO data. During Stage 1, which assessed the feasibility of recruitment and data collection, 102 patients were recruited at 22 sites with representation from patient groups frequently excluded in OS studies, including patients over 50 years and those with less common primary sites. The feasibility of collecting clinical and biological samples, in addition to PRO data, has been established and there is ongoing analysis of these data as part of Stage 2. ICONIC will provide a unique, prospective cohort of newly diagnosed OS patients representative of the UK patient population, with fully annotated clinical outcomes linked to molecularly characterised biospecimens, allowing for comprehensive analyses to better understand biology and develop new biomarkers and novel therapeutic approaches.
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Background: People in prison experience poorer mental and physical health compared to their peers in the general population. The causes are multi-dimensional ranging from lifestyle factors to poorer access to healthcare. Little is known about cancer in people in prison or how the cost of their care compares to the general population. Methods: Data on people diagnosed with cancer while in English prisons were identified in National Cancer Registration dataset and linked to Hospital Episode Statistics (HES) for the years 2012-2017. General population matched patients were identified using a 1-5 ratio, based on age, gender, year of diagnosis, cancer type and disease stage. Outpatient and inpatient HES data up to six-months from diagnosis were costed using NHS Reference costs and inflated to 2017/2018 costs. Findings: 879 prison and 4326 general population cancer diagnoses were identified in HES. The adjusted six-month cost of cancer care was significantly lower for people in prison (-£1216.95% confidence interval (CI) -1638 to -795), driven by fewer outpatient attendances. However, people diagnosed in prison had higher emergency care costs (£497.95% CI 375-619). Security escorts further increased the total cost of care. Interpretation: Following a cancer diagnosis, people in English prisons have significantly lower planned care costs, but higher emergency care costs and an overall higher cost due to security escorts. Further work is required to identify ways of improving cancer care for people in prisons to ensure it is equivalent to that received by the general population. Funding: National Institute for Health and Social Care Research 16/52/53.
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Background: Approximately 82,000 people are in prison annually in England and Wales. Limited research has investigated cancer in this population and none has explored experiences of imprisoned people with cancer. This study aimed to address this gap. Methods: We conducted 55 semi-structured, qualitative, audio-recorded interviews with: imprisoned people with cancer (n = 24), custodial staff (n = 6), prison healthcare staff (n = 16) and oncology specialists (n = 9). Data were collected 07/10/2019-20/03/2020. Patients were recruited by prison healthcare staff and interviews were conducted face-to-face. Professionals were recruited via professional networks and interviews were conducted face-to-face or via telephone. Transcribed interviews were analysed using reflexive thematic analysis. We also analysed relevant National Cancer Patient Experience Survey (NCPES) questions for those diagnosed in prison (n = 78) and in the general population (n = 390). Findings: Our findings highlight the complexities of cancer care for imprisoned people. We identified three core themes: control and choice, communication, and care and custody. Whilst people in prison follow a similar diagnostic pathway to those in the community, additional barriers to diagnosis exist including health literacy, the General Practitioner appointment booking system and communication between prison and oncology staff. Tensions between control and choice in prison impacted aspects of cancer care experience such as symptom management and accessing cancer information. NCPES results supported the qualitative findings and showed people in prison reported significantly poorer experiences than in the general population. Interpretation: Our findings demonstrate the complexity of cancer care in custodial settings, identifying barriers and enablers to equitable cancer care provision and offering insights on how to improve care for this population. Funding: National Institute for Health and Social Care Research Delivery Research Programme 16/52/53 and Strategic Priorities Fund 2019/20 Research England via University of Surrey.
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Affordable thin-film composite (TFC) membranes are a potential alternative to more expensive ion exchange membranes in saltwater electrolyzers used for hydrogen gas production. We used a solution-friction transport model to study how the induced potential gradient controls ion transport across the polyamide (PA) active layer and support layers of TFC membranes during electrolysis. The set of parameters was simplified by assigning the same size-related partition and friction coefficients for all salt ions through the membrane active layer. The model was fit to experimental ion transport data from saltwater electrolysis with 600 mM electrolytes at a current density of 10 mA cm-2. When the electrolyte concentration and current density were increased, the transport of major charge carriers was successfully predicted by the model. Ion transport calculated using the model only minimally changed when the negative active layer charge density was varied from 0 to 600 mM, indicating active layer charge was not largely responsible for controlling ion crossover during electrolysis. Based on model simulations, a sharp pH gradient was predicted to occur within the supporting layer of the membrane. These results can help guide membrane design and operation conditions in water electrolyzers using TFC membranes.
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Eletrólise , Transporte de Íons , Membranas Artificiais , Água/químicaRESUMO
In the past decade, next-generation sequencing (NGS) has revolutionised genetic diagnostics for rare neurological disorders (RND). However, the lack of standardised technical, interpretative, and reporting standards poses a challenge for ensuring consistent and high-quality diagnostics globally. To address this, the European Reference Network for Rare Neurological Diseases (ERN-RND) collaborated with the European Molecular Genetics Quality Network (EMQN) to establish an external quality assessment scheme for NGS-based diagnostics in RNDs. The scheme, initiated in 2021 with a pilot involving 29 labs and followed by a second round in 2022 with 42 labs, aimed to evaluate the performance of laboratories in genetic testing for RNDs. Each participating lab analysed genetic data from three hypothetical cases, assessing genotyping, interpretation, and clerical accuracy. Despite a majority of labs using exome or genome sequencing, there was considerable variability in gene content, sequencing quality, adherence to standards, and clinical guidance provision. Results showed that while most labs provided correct molecular diagnoses, there was significant variability in reporting technical quality, adherence to interpretation standards, reporting strategies, and clinical commentary. Notably, some labs returned results with the potential for adverse medical outcomes. This underscores the need for further harmonisation, guideline development, and external quality assessment in the evolving landscape of genomic diagnostics for RNDs. Overall, the experience with the scheme highlighted the generally good quality of participating labs but emphasised the imperative for ongoing improvement in data analysis, interpretation, and reporting to enhance patient safety.
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Testes Genéticos , Doenças do Sistema Nervoso , Doenças Raras , Humanos , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/diagnóstico , Doenças Raras/genética , Doenças Raras/diagnóstico , Europa (Continente) , Testes Genéticos/normas , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/normas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Garantia da Qualidade dos Cuidados de Saúde/normasRESUMO
BACKGROUND: Race and sex differences are not consistently reported in the literature. Fundamentally, anatomical differences of cervical neuroforaminal dimensions (CNFD) amongst these groups would be important to know. PURPOSE: To establish normative radiographic morphometric measurements of CNFD and uncover the influence of patient sex, race, and ethnicity while also considering anthropometric characteristics. STUDY DESIGN: Retrospective radiographic morphometric study. PATIENT SAMPLE: A total of 1,000 patients between 18 and 35 years of age who were free of spinal pathology. OUTCOME MEASURES: Foraminal height, axial width, and area of cervical neural foramen. METHODS: Cervical CTs were reviewed to measure CNFD, defined as follows: foraminal height, axial width, and area. Statistical analyses were performed to assess associations between CNFD, and patient height, weight, sex, race, and ethnicity. RESULTS: CNFD measurements followed a bimodal distribution pattern moving caudally from C2-T1. Irrespective of disc level, cervical CNFD were as follows: left and right widths of 6.6±1.5 and 6.6±1.5 mm, heights of 9.4±2.4 and 9.4±3.2 mm, and areas of 60.0±19.5 and 60.6±20.7 mm2. Left and right foraminal width were highest at C2-C3 and lowest at C3-C4. Left and right foraminal height were highest at C7-T1 and C6-C7, respectively and lowest at C3-C4. Left and right foraminal areas were highest at C2-C3 and lowest at C3-C4. Significant differences were observed for all CNFD measurements across disc levels. CNFD did not vary based on laterality. Significant CNFD differences were observed with respect to patient sex, race, and ethnicity. Male height and area were larger compared to females. In contrast, female foraminal width was larger compared to males. The Asian cohort demonstrated the largest foraminal widths. White and Hispanic patients demonstrated the largest foraminal heights and areas. Black patients demonstrated the smallest foraminal widths, heights, and areas. Patient height and weight were only weakly correlated with CNFD measurements across all levels from C2-T1. CONCLUSIONS: This study describes 36,000 normative measurements of 12,000 foramina from C2-T1. CNFD measurements vary based on disc level, but not laterality. Contrasting left- versus right-sided neuroforamina of the same level may aid in determining the presence of unilateral stenosis. Patient sex, race, and ethnicity are associated with CNFD, while patient anthropometric factors are weakly correlated with CNFD.
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BACKGROUND: The growing and ageing prison population in England makes accurate cancer data of increasing importance for prison health policies. This study aimed to compare cancer incidence, treatment, and survival between patients diagnosed in prison and the general population. METHODS: In this population-based, matched cohort study, we used cancer registration data from the National Cancer Registration and Analysis Service in England to identify primary invasive cancers and cervical cancers in situ diagnosed in adults (aged ≥18 years) in the prison and general populations between Jan 1, 1998, and Dec 31, 2017. Ministry of Justice and Office for National Statistics population data for England were used to calculate age-standardised incidence rates (ASIR) per year and age-standardised incidence rate ratios (ASIRR) for the 20-year period. Patients diagnosed with primary invasive cancers (ie, excluding cervical cancers in situ) in prison between Jan 1, 2012, and Dec 31, 2017 were matched to individuals from the general population and linked to hospital and treatment datasets. Matching was done in a 1:5 ratio according to 5-year age group, gender, diagnosis year, cancer site, and disease stage. Our primary objectives were to compare the incidence of cancer (1998-2017); the receipt of treatment with curative intent (2012-17 matched cohort), using logistic regression adjusted for matching variables (excluding cancer site) and route to diagnosis; and overall survival following cancer diagnosis (2012-17 matched cohort), using a Cox proportional hazards model adjusted for matching variables (excluding cancer site) and route to diagnosis, with stratification for the receipt of any treatment with curative intent. FINDINGS: We identified 2015 incident cancers among 1964 adults (1556 [77·2%] men and 459 [22·8%] women) in English prisons in the 20-year period up to Dec 31, 2017. The ASIR for cancer for men in prison was initially lower than for men in the general population (in 1998, ASIR 119·33 per 100â000 person-years [95% CI 48·59-219·16] vs 746·97 per 100â000 person-years [742·31-751·66]), but increased to a similar level towards the end of the study period (in 2017, 856·85 per 100â000 person-years [675·12-1060·44] vs 788·59 per 100â000 person-years [784·62-792·57]). For women, the invasive cancer incidence rate was low and so ASIR was not reported for this group. Over the 20-year period, the incidence of invasive cancer for men in prison increased (incidence rate ratio per year, 1·05 [95% CI 1·04-1·06], during 1999-2017 compared with 1998). ASIRRs showed that over the 20-year period, overall cancer incidence was lower in men in prison than in men in the general population (ASIRR 0·76 [95% CI 0·73-0·80]). The difference was not statistically significant for women (ASIRR 0·83 [0·68-1·00]). Between Jan 1, 2012, and Dec 31, 2017, patients diagnosed in prison were less likely to undergo curative treatment than matched patients in the general population (274 [32·3%] of 847 patients vs 1728 [41·5%] of 4165; adjusted odds ratio (OR) 0·72 [95% CI 0·60-0·85]). Being diagnosed in prison was associated with a significantly increased risk of death on adjustment for matching variables (347 deaths during 2021·9 person-years in the prison cohort vs 1626 deaths during 10â944·2 person-years in the general population; adjusted HR 1·16 [95% CI 1·03-1·30]); this association was partly explained by stratification by curative treatment and further adjustment for diagnosis route (adjusted HR 1·05 [0·93-1·18]). INTERPRETATION: Cancer incidence increased in people in prisons in England between 1998 and 2017, with patients in prison less likely to receive curative treatments and having lower overall survival than the general population. The association with survival was partly explained by accounting for differences in receipt of curative treatment and adjustment for diagnosis route. Improved routine cancer surveillance is needed to inform prison cancer policies and decrease inequalities for this under-researched population. FUNDING: UK National Institute for Health and Care Research, King's College London, and Strategic Priorities Fund 2019/20 of Research England via the University of Surrey.
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Neoplasias , Prisioneiros , Humanos , Feminino , Masculino , Inglaterra/epidemiologia , Incidência , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/mortalidade , Neoplasias/terapia , Adulto , Prisioneiros/estatística & dados numéricos , Idoso , Adulto Jovem , Adolescente , Prisões/estatística & dados numéricos , Estudos de Coortes , Sistema de Registros/estatística & dados numéricosRESUMO
BACKGROUND: Gut microbiome modulation to boost antitumor immune responses is under investigation. METHODS: ROMA-2 evaluated the microbial ecosystem therapeutic (MET)-4 oral consortia, a mixture of cultured human stool-derived immune-responsiveness associated bacteria, given with chemoradiation (CRT) in HPV-related oropharyngeal cancer patients. Co-primary endpoints were safety and changes in stool cumulative MET-4 taxa relative abundance (RA) by 16SRNA sequencing. Stools and plasma were collected pre/post-MET-4 intervention for microbiome and metabolome analysis. RESULTS: Twenty-nine patients received ≥1 dose of MET-4 and were evaluable for safety: drug-related adverse events (AEs) occurred in 13/29 patients: all grade 1-2 except one grade 3 (diarrhea). MET-4 was discontinued early in 7/29 patients due to CRT-induced toxicity, and in 1/29 due to MET-4 AEs. Twenty patients were evaluable for ecological endpoints: there was no increase in stool MET-4 RA post-intervention but trended to increase in stage III patients (p = 0.06). MET-4 RA was higher in stage III vs I-II patients at week 4 (p = 0.03) and 2-month follow-up (p = 0.01), which correlated with changes in plasma and stool targeted metabolomics. CONCLUSIONS: ROMA-2 did not meet its primary ecologic endpoint, as no engraftment was observed in the overall cohort. Exploratory findings of engraftment in stage III patients warrants further investigation of microbiome interventions in this subgroup.
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Quimiorradioterapia , Microbioma Gastrointestinal , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/microbiologia , Neoplasias Orofaríngeas/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Idoso , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Adulto , Fezes/microbiologiaRESUMO
BACKGROUND: Artificial airways are essential in various clinical settings to maintain a patient's airway and provide necessary support for ventilation and oxygenation. These devices are commonly temporary and come in several types, each serving specific purposes. Understanding the indications, types, and proper care of artificial airways is crucial for health care professionals to ensure patients receive optimal care and prevent complications. OBJECTIVE: This article aims to review the indications for using artificial airways and discuss the most commonly used types, including supraglottic airway devices, endotracheal tubes, tracheostomy tubes, and laryngectomy tubes. It also provides insights into the procedures involved in intubation and percutaneous tracheostomy and offers guidance on patient management, emphasizing assessment, oral care, suctioning, and humidification for patients with these airway devices. CONCLUSION: This article underscores the significance of understanding artificial airways, not just as a set of skills but as a commitment to patient welfare. Health care professionals who master the knowledge and care of these devices can significantly contribute to their patients' well-being and quality of life.
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Intubação Intratraqueal , Traqueostomia , Humanos , Traqueostomia/enfermagem , Intubação Intratraqueal/enfermagem , Manuseio das Vias Aéreas/métodos , Respiração ArtificialRESUMO
OBJECTIVE: To examine the origin of cervical vestibular evoked myogenic potential (cVEMP) late waves (n34-p44) elicited with air-conducted click stimuli. DESIGN: Using a retrospective design, cVEMPs from normal volunteers were compared to those obtained from patients with vestibular and auditory pathologies. STUDY SAMPLE: (1) Normal volunteers (n = 56); (2) severe-to-profound sensorineural hearing loss (SNHL) with normal vestibular function (n = 21); (3) peripheral vestibular impairment with preserved hearing (n = 16); (4) total vestibulocochlear deficit (n = 23). RESULTS: All normal volunteers had ipsilateral-dominant early p13-n23 peaks. Late peaks were present bilaterally in 78%. The p13-n23 response was present in all patients with SNHL but normal vestibular function, and 43% had late waves. Statistical comparison of these patients to a subset of age-matched controls showed no significant difference in the frequencies, amplitudes or latencies of their ipsilateral early and late peaks. cVEMPs were absent in all patients with vestibular impairment. CONCLUSION: The presence of long-latency cVEMP waves was not dependent on the integrity of sensorineural hearing pathways, but instead correlated with intact vestibular function. This finding conflicts with the view that these late waves are cochlear in origin, and suggests that vestibular afferents may assume a more prominent role in their generation.
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INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.
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Hipertensão Induzida pela Gravidez , Humanos , Gravidez , Feminino , Austrália , Nova Zelândia , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/terapia , Hipertensão Induzida pela Gravidez/prevenção & controle , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/prevenção & controle , Pré-Eclâmpsia/terapia , Sociedades Médicas , Obstetrícia/normas , Anti-Hipertensivos/uso terapêutico , Guias de Prática Clínica como AssuntoRESUMO
INTRODUCTION: How to communicate effectively with adolescent and young adults with cancer (AYACs) is a research priority. In a UK-wide survey of young people with cancer's research priorities, communication was a striking cross-cutting theme. It is increasingly recognised that AYACs have experiences and communication needs that differ significantly from those of younger children and older adults. The purpose of this review is to explore the features of effective clinical communication with AYACs. METHODS: A literature search was undertaken to identify and map the available evidence using a broad scope to get an overview of the pertinent literature, identify knowledge gaps and clarify concepts. The searches yielded 5825 records, generating 4040 unique articles. These were screened and 71 full articles were read by four researchers with disagreements resolved by discussion leaving 29 included articles. Narrative synthesis was undertaken in relation to each of the research questions. RESULTS: Three key themes were identified: being an adolescent/young adult, supporters, and healthcare professionals (HCPs). AYACs need to feel that HCPs understand their unique perspective. They want to be involved, this changes over time and in different contexts. Supporters are a central tenet, are most often parents and undertake several roles which are not always universally supportive. HCPs enable involvement of AYACs, and this needs to be actively promoted. AYACs preference for their level of involvement requires continual assessment. The three themes are interlinked and exist within the wider scope of the triadic encounter and cancer experience. CONCLUSION: Supporters, most often parents were a key feature across the data and were seemingly paradoxical in nature. Triadic communication, the presence of a third person, is a central tenet of communication with AYACs and we propose a conceptual model to represent the nuances, components, and facets of this complex communication.
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Comunicação , Neoplasias , Criança , Humanos , Adolescente , Adulto Jovem , Idoso , Narração , Emoções , Pessoal de Saúde , Neoplasias/terapiaRESUMO
BACKGROUND: Family relationships and social networks are critically important to adolescents and young adults (AYAs) with cancer, impacting their experience and well-being throughout the cancer trajectory. A cancer diagnosis impacts the development of independence and an adult identity, which can present challenges to psychosocial well-being needs and relationships between caregivers and AYAs. OBJECTIVE: The aim of this study was to explore the psychosocial and support needs of the main caregivers of AYAs. METHODS: This is a secondary analysis of the BRIGHTLIGHT caregiver survey, exploring items pertaining to support offered/engaged with, appraisal of helpfulness, and caregivers' emotional and psychological distress experience. Descriptive statistics, a correlational analysis, and a 1-way analysis of variance were conducted. RESULTS: There were 518 caregiver responses (62%). Over half received information about their caregiving needs, with the majority finding this very/fairly helpful. Most (80%) of those who had not received the information would have valued it. High levels of negative emotional and psychological well-being were reported, with 91% feeling depressed or anxious since the AYAs' diagnosis and 41% always/often experiencing these feelings. Total distress was associated with being younger, a parent, female, and unemployed, and earning a below-average income. CONCLUSIONS: The needs of caregivers are broad and multidimensional; however, some characteristics were associated with higher distress. When caregiver-specific information was provided by healthcare professionals, it was well received. IMPLICATIONS FOR PRACTICE: Healthcare professionals should consider caregivers' needs individually and provide/signpost to support. Caregivers need to be involved in designing and implementing future research, given the heterogeneity of needs identified.
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The biographical disruption that occurs in adolescents and young adults following a cancer diagnosis can affect various important psychosocial domains including relationships with family and friends, sexual development, vocational and educational trajectories, and physical and emotional wellbeing. While there is evidence of the physical impact of cancer during this period, less is known about the impact on emotional wellbeing and especially on the barriers for young people accessing help and support. We aimed to obtain a more in-depth understanding of young people's experiences of their diagnosis, treatment, psychological impact, and range of resources they could or wanted to access for their mental health. We conducted an in-depth qualitative study using semi-structured interviews with 43 young people who had developed cancer aged 16 to 39 years and were either within 6 months of diagnosis or 3-5 years after treatment had ended. Framework analysis identified three themes: the emotional impact of cancer (expressed through anxiety, anger, and fear of recurrence); personal barriers to support through avoidance; and support to improve mental health through mental health services or adolescent and young adult treatment teams. We showed the barriers young people have to access care, particularly participant avoidance of support. Interrupting this process to better support young people and provide them with flexible, adaptable, consistent, long-term psychological support has the potential to improve their quality of life and wellbeing.
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The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13 to 82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the global quality of life scale and 18% of the Toronto Extremity Salvage Scale (TESS); so psychometrically, it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed.
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BACKGROUND: Plexins are large transmembrane receptors for the semaphorin family of signalling proteins. Semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Nine plexin genes have been identified in humans, but despite the apparent importance of plexins in development, only biallelic PLXND1 and PLXNA1 variants have so far been associated with Mendelian genetic disease. METHODS: Eight individuals from six families presented with a recessively inherited variable clinical condition, with core features of amelogenesis imperfecta (AI) and sensorineural hearing loss (SNHL), with variable intellectual disability. Probands were investigated by exome or genome sequencing. Common variants and those unlikely to affect function were excluded. Variants consistent with autosomal recessive inheritance were prioritised. Variant segregation analysis was performed by Sanger sequencing. RNA expression analysis was conducted in C57Bl6 mice. RESULTS: Rare biallelic pathogenic variants in plexin B2 (PLXNB2), a large transmembrane semaphorin receptor protein, were found to segregate with disease in all six families. The variants identified include missense, nonsense, splicing changes and a multiexon deletion. Plxnb2 expression was detected in differentiating ameloblasts. CONCLUSION: We identify rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and SNHL as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. The variable syndromic human phenotype overlaps with that seen in Plxnb2 knockout mice, and, together with the rarity of human PLXNB2 variants, may explain why pathogenic variants in PLXNB2 have not been reported previously.
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Amelogênese Imperfeita , Deficiência Intelectual , Linhagem , Humanos , Animais , Masculino , Feminino , Camundongos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Amelogênese Imperfeita/genética , Amelogênese Imperfeita/patologia , Receptores de Superfície Celular/genética , Proteínas do Tecido Nervoso/genética , Alelos , Criança , Perda Auditiva/genética , Perda Auditiva/patologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/patologia , Adulto , Mutação/genética , Adolescente , Pré-Escolar , FenótipoRESUMO
OBJECTIVES: Clinical communication needs of teenagers and young adults with cancer (TYACs) are increasingly recognised to differ significantly from younger children and older adults. We sought to understand who is present with TYACs, TYACs' experiences of triadic communication and its impact. We generated three research questions to focus this review: (1) Who is present with TYACs in healthcare consultations/communication?, (2) What are TYACs' experiences of communication with the supporter present? and (3) What is the impact of a TYAC's supporter being present in the communication? DESIGN: Systematic review with narrative synthesis. DATA SOURCES: The search was conducted across six databases: Medline, CINAHL, Embase, PsycINFO, Web of Science and AMED for all publications up to December 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Included papers were empirical research published after 2005; participants had malignant disease, diagnosed aged 13-24 years (for over 50% of participants); the research addressed any area of clinical communication. DATA EXTRACTION AND SYNTHESIS: Three independent reviewers undertook full-text screening. A review-specific data extraction form was used to record participant characteristics and methods from each included paper and results relevant to the three review questions. RESULTS: A total of 8480 studies were identified in the search, of which 36 fulfilled the inclusion criteria. We found that mothers were the most common supporter present in clinical communication encounters. TYACs' experiences of triadic communication are paradoxical in nature-the supporter can help or hinder the involvement of the young person in care-related communication. Overall, young people are not included in clinical communication and decisions at their preferred level. CONCLUSION: Triadic communication in TYACs' care is common, complex and dynamic. Due to the degree of challenge and nuances raised, healthcare professionals need further training on effective triadic communication. PROSPERO REGISTRATION NUMBER: CRD42022374528.
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Comunicação , Neoplasias , Humanos , Adolescente , Neoplasias/psicologia , Adulto Jovem , Relações Médico-PacienteRESUMO
Purpose: In England, health care policy promotes specialized age-appropriate cancer services for teenagers and young adults (TYA), for those aged 13-24 years at diagnosis. Specialist Principal Treatment Centers (PTCs) provide enhanced age-specific care for TYA, although many still receive all or some of their care in adult or children's cancer services. Our aim was to determine the patient-reported outcomes associated with TYA-PTC based care. Methods: We conducted a multicenter cohort study, recruiting 1114 TYA aged 13-24 years at diagnosis. Data collection involved a bespoke survey at 6,12,18, 24, and 36 months after diagnosis. Confounder adjusted analyses of perceived social support, illness perception, anxiety and depression, and health status, compared patients receiving NO-TYA-PTC care with those receiving ALL-TYA-PTC and SOME-TYA-PTC care. Results: Eight hundred and thirty completed the first survey. There was no difference in perceived social support, anxiety, or depression between the three categories of care. Significantly higher illness perception was observed in the ALL-TYA-PTC and SOME-TYA-PTC group compared to the NO-TYA-PTC group, (adjusted difference in mean (ADM) score on Brief Illness Perception scale 2.28 (95% confidence intervals [CI] 0.48-4.09) and 2.93 [1.27-4.59], respectively, p = 0.002). Similarly, health status was significantly better in the NO-TYA-PTC (ALL-TYA-PTC: ADM -0.011 [95%CI -0.046 to 0.024] and SOME-TYA-PTC: -0.054 [-0.086 to -0.023]; p = 0.006). Conclusion: The reason for the difference in perceived health status is unclear. TYA who accessed a TYA-PTC (all or some care) had higher perceived illness. This may reflect greater education and promotion of self-care by health care professionals in TYA units.
Assuntos
Medidas de Resultados Relatados pelo Paciente , Humanos , Adolescente , Masculino , Feminino , Adulto Jovem , Inglaterra , Adulto , Estudos de Coortes , Neoplasias/psicologia , Neoplasias/terapiaRESUMO
Hydrogen gas evolution using an impure or saline water feed is a promising strategy to reduce overall energy consumption and investment costs for on-site, large-scale production using renewable energy sources. The chlorine evolution reaction is one of the biggest concerns in hydrogen evolution with impure water feeds. The "alkaline design criterion" in impure water electrolysis was examined here because water oxidation catalysts can exhibit a larger kinetic overpotential without interfering chlorine chemistry under alkaline conditions. Here, we demonstrated that relatively inexpensive thin-film composite (TFC) membranes, currently used for high-pressure reverse osmosis (RO) desalination applications, can have much higher rejection of Cl- (total crossover of 2.9 ± 0.9 mmol) than an anion-exchange membrane (AEM) (51.8 ± 2.3 mmol) with electrolytes of 0.5 M KOH for the anolyte and 0.5 M NaCl for the catholyte with a constant current (100 mA/cm2 for 20 h). The membrane resistances, which were similar for the TFC membrane and the AEM based on electrochemical impedance spectroscopy (EIS) and Ohm's law methods, could be further reduced by increasing the electrolyte concentration or removal of the structural polyester supporting layer (TFC-no PET). TFC membranes could enable pressurized gas production, as this membrane was demonstrated to be mechanically stable with no change in permeate flux at 35 bar. These results show that TFC membranes provide a novel pathway for producing green hydrogen with a saline water feed at elevated pressures compared to systems using AEMs or porous diaphragms.