RESUMO
BACKGROUND: Our aim was to develop a validated Patient Reported Experience Measure (PREM) to capture patient and carer experience during participation in experimental cancer medicine trials (ECM): called PREM-ECM. METHODS: Mixed method design, consisting of four stages. Questionnaire items were produced for both patients and carers using interviews, focus groups, and cognitive interviews with patients and carers separately. For both patient and carer PREMs, a cross-sectional questionnaire study was conducted to identify final items for inclusion using hierarchical item reduction and Rasch analysis. Questionnaire validity and reliability were assessed, including administration feasibility. RESULTS: Initial interview participants suggested the need for three PREMs, two specific to patients: (i) a 'prior' questionnaire that captured experiences of trial introduction, screening, consenting, and early trial experience (< 6 weeks post consent); and (ii) 'on-trial' that captured experiences of ongoing consent and trial participation; and (iii) a PREM specific for carers. The draft 25-item 'prior' questionnaire was completed by 162 patients and 162 patients completed the draft 35-item 'on-trial' questionnaire. Hierarchical and Rasch analysis produced a 14-item 'prior' list and a 15-item list for 'on-trial'. Both patient PREM's demonstrated a good fit to the Rasch model following Bonferroni correction (X2p = 0.008). The carer 34-draft item questionnaire was completed by 102 participants. Hierarchical and Rasch analysis produced a 13-item list for PREM-ECM-Carer, with good fit to the Rasch model ( X2p = 0.62). The pilot testing demonstrated the feasibility of all the PREMs in capturing patient and caregiver experiences in routine clinical settings. CONCLUSIONS: The three PREM-ECM questionnaires will be the first validated experience measures for ECM trial patients and their carers. These questionnaires may be used to assess patients' and their carers' experiences of ECM and enable robust comparisons across cancer trial units highlighting areas for service improvement.
Assuntos
Cuidadores , Neoplasias , Humanos , Cuidadores/psicologia , Reprodutibilidade dos Testes , Estudos Transversais , Inquéritos e Questionários , Neoplasias/tratamento farmacológico , Medidas de Resultados Relatados pelo PacienteRESUMO
The use of digital technologies as a method of delivering health behaviour change (HBC) interventions is rapidly increasing across the general population. However, the role in severe mental illness (SMI) remains overlooked. In this study, we aimed to systematically identify and evaluate all of the existing evidence around digital HBC interventions in people with an SMI. A systematic search of online electronic databases was conducted. Data on adherence, feasibility, and outcomes of studies on digital HBC interventions in SMI were extracted. Our combined search identified 2196 titles and abstracts, of which 1934 remained after removing duplicates. Full-text screening was performed for 107 articles, leaving 36 studies to be included. From these, 14 focused on physical activity and/or cardio-metabolic health, 19 focused on smoking cessation, and three concerned other health behaviours. The outcomes measured varied considerably across studies. Although over 90% of studies measuring behavioural changes reported positive changes in behaviour/attitudes, there were too few studies collecting data on mental health to determine effects on psychiatric outcomes. Digital HBC interventions are acceptable to people with an SMI, and could present a promising option for addressing behavioural health in these populations. Feedback indicated that additional human support may be useful for promoting adherence/engagement, and the content of such interventions may benefit from more tailoring to specific needs. While the literature does not yet allow for conclusions regarding efficacy for mental health, the available evidence to date does support their potential to change behaviour across various domains.
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Transtornos Mentais , Abandono do Hábito de Fumar , Humanos , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Exercício Físico , Sintomas ComportamentaisRESUMO
Tobacco smoking is highly prevalent among patients with serious mental illness (SMI), with known deleterious consequences. Smoking cessation is therefore a prioritary public health challenge in SMI. In recent years, several smoking cessation digital interventions have been developed for non-clinical populations. However, their impact in patients with SMI remains uncertain. We conducted a systematic review to describe and evaluate effectiveness, acceptability, adherence, usability and safety of digital interventions for smoking cessation in patients with SMI. PubMed/MEDLINE, EMBASE, CINAHL, Web of Science, PsychINFO and the Cochrane Tobacco Addiction Group Specialized Register were searched. Studies matching inclusion criteria were included and their information systematically extracted by independent investigators. Thirteen articles were included, which reported data on nine different digital interventions. Intervention theoretical approaches ranged from mobile contingency management to mindfulness. Outcome measures varied widely between studies. The highest abstinence rates were found for mSMART MIND (7-day point-prevalent abstinence: 16-40%). Let's Talk About Quitting Smoking reported greater acceptability ratings, although this was not evaluated with standardized measures. Regarding usability, Learn to Quit showed the highest System Usability Scale scores [mean (s.d.) 85.2 (15.5)]. Adverse events were rare and not systematically reported. Overall, the quality of the studies was fair to good. Digitally delivered health interventions for smoking cessation show promise for improving outcomes for patients with SMI, but lack of availability remains a concern. Larger trials with harmonized assessment measures are needed to generate more definitive evidence and specific recommendations.
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Transtornos Mentais , Abandono do Hábito de Fumar , Fumar Tabaco , Humanos , Abandono do Hábito de Fumar/métodos , Fumar Tabaco/efeitos adversos , Telemedicina , Transtornos Mentais/complicações , Transtornos Mentais/terapia , Atenção PlenaRESUMO
OBJECTIVES: Approximately 10 to 35% of people with a hearing impairment own a hearing aid. The present study aims to identify barriers to obtaining a hearing aid and inform future interventions by examining the biopsychosocial characteristics of adults aged 50+ according to 7 categories: (i) Did not report hearing difficulties, (ii) Reported hearing difficulties, (iii) Told a healthcare professional about experiencing hearing difficulties, (iv) Referred for a hearing assessment, (v) Offered a hearing aid, (vi) Accepted a hearing aid, and (vii) Reported using a hearing aid regularly. DESIGN: The research was conducted using the English Longitudinal Study of Aging wave 7 with data obtained from 9666 adults living in England from June 2014 to May 2015. Cross-sectional data were obtained from a subset of 2845 participants aged 50 to 89 years of age with a probable hearing impairment measured by hearing screening (indicating a hearing threshold of >20 dB HL at 1 kHz or >35 dB HL at 3 kHz in the better ear). Classification according to hearing health-seeking category was via participants' self-report. Participants in each category were compared with people in all subsequent categories to examine the associations between each category and biopsychosocial correlates (sex, age, ethnicity, educational level, wealth, audiometric hearing level, self-reported health status, cognitive performance, attitudes to aging, living alone, and engagement in social activities) using multiple logistic regression. RESULTS: The proportions of individuals (N = 2845) in categories i to vii were 40.0% (n = 1139), 14.0% (n = 396), 4.5% (n = 129), 4.0% (n = 114), 1.2% (n = 34), 7.7% (n = 220), and 28.6% (n = 813), respectively. Severity of hearing impairment was the only factor predictive of all the categories of hearing health-seeking that could be modeled. Other correlates predictive of at least one category of hearing health-seeking included sex, age, self-reported heath, participation in social activities, and cognitive function. CONCLUSIONS: For the first time, it was shown that 40.0% of people with an audiometrically identified probable hearing impairment did not report hearing difficulties. Each of the five categories of hearing health-seeking that could be modeled had different drivers and consequently, interventions likely should vary depending on the category of hearing health-seeking.
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Testes Auditivos , Audição , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Inglaterra/epidemiologia , Humanos , Estudos Longitudinais , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Self-harm amongst young people is an increasing problem, with looked-after young people at higher risk. Despite this, little research exists on what young people who self-harm find helpful. METHOD: One hundred and twenty-six 11-21 year olds (53 who had experience of the care system and 73 who did not) were recruited from the community and NHS. All participants had self-harmed in the past 6 months. Participants completed an Audio Computer-Assisted Self-interview (ACASI) regarding their views about the support they had received, how helpful it was, and what further help they felt they needed. RESULTS: Looked-after young people reported the three most helpful sources of support were Child and Adolescent Mental Health Services (CAMHS), friends and pets and the least helpful were CAMHS, Accident and Emergency (A&E) and Social services. For non-looked-after young people, CAMHS, counselling and Harmless (user-led support service for self-harm) were most helpful and CAMHS, cognitive behavioural therapy (CBT) and general practitioner (GP) were the least. Compared with the other group, more looked-after young people had received help from A&E and CAMHS, whereas more non-looked-after young people had accessed GPs, parents, psychological therapies, self-help books and websites. More looked-after young people found support groups helpful, and more non-looked-after young people reported that distraction techniques, medication and their siblings were helpful. CONCLUSION: Young people who self-harm have mixed views about CAMHS. Differences in the pattern of access and preferences for support between looked-after and non-looked-after young people should be reflected in service availability and commissioning. KEY PRACTITIONER MESSAGE: Little is known about what young people who self-harm find helpful, particularly for looked-after young people. CAMHS was named amongst the most helpful and the least helpful services by both looked-after and non-looked-after young people. Social services and A&E were frequently cited amongst the least helpful sources of support. Young people report finding informal support helpful, including family and friends. There appears to be a need for explorations of the reasons behind the apparent negative perception of statutory services in young people, and what is required to shift that.
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Serviços de Saúde Mental , Comportamento Autodestrutivo , Adolescente , Adulto , Criança , Terapia Cognitivo-Comportamental , Humanos , Psicologia do Adolescente , Psicologia da Criança , Pesquisa Qualitativa , Comportamento Autodestrutivo/psicologia , Comportamento Autodestrutivo/terapia , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVES: Hearing impairment is ranked fifth globally for years lived with disability, yet hearing aid use is low among individuals with a hearing impairment. Identifying correlates of hearing aid use would be helpful in developing interventions to promote use. To date, however, no studies have investigated a wide range of variables, this has limited intervention development. The aim of the present study was to identify correlates of hearing aid use in adults in the United Kingdom with a hearing impairment. To address limitations in previous studies, we used a cross-sectional analysis to model a wide range of potential correlates simultaneously to provide better evidence to aid intervention development. DESIGN: The research was conducted using the UK Biobank Resource. A cross-sectional analysis of hearing aid use was conducted on 18,730 participants aged 40 to 69 years old with poor hearing, based on performance on the Digit Triplet test. RESULTS: Nine percent of adults with poor hearing in the cross-sectional sample reported using a hearing aid. The strongest correlate of hearing aid use was self-reported hearing difficulties (odds ratio [OR] = 110.69 [95% confidence interval {CI} = 65.12 to 188.16]). Individuals who were older were more likely to use a hearing aid: for each additional year of age, individuals were 5% more likely to use a hearing aid (95% CI = 1.04 to 1.06). People with tinnitus (OR = 1.43 [95% CI = 1.26 to 1.63]) and people with a chronic illness (OR = 1.97 [95% CI = 1.71 to 2.28]) were more likely to use a hearing aid. Those who reported an ethnic minority background (OR = 0.53 [95% CI = 0.39 to 0.72]) and those who lived alone (OR = 0.80 [95% CI = 0.68 to 0.94]) were less likely to use a hearing aid. CONCLUSIONS: Interventions to promote hearing aid use need to focus on addressing reasons for the perception of hearing difficulties and how to promote hearing aid use. Interventions to promote hearing aid use may need to target demographic groups that are particularly unlikely to use hearing aids, including younger adults, those who live alone and those from ethnic minority backgrounds.
Assuntos
Etnicidade/estatística & dados numéricos , Auxiliares de Audição/estatística & dados numéricos , Perda Auditiva/reabilitação , Grupos Minoritários/estatística & dados numéricos , Participação Social , Zumbido/epidemiologia , Adulto , Fatores Etários , Idoso , Doença Crônica , Estudos Transversais , Feminino , Perda Auditiva/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Características de Residência/estatística & dados numéricos , Autorrelato , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: The present study investigated: (a) how motivated patients are to use their hearing aid, and (b) whether post-motivational variables (e.g. action planning, coping planning) have anything to offer in terms of developing interventions to boost hearing aid use. DESIGN: participants completed a questionnaire designed to tap Health Action Process Approach constructs prior to their hearing aid prescription and fitting. STUDY SAMPLE: Sixty-seven patients attending NHS audiology clinics. RESULTS: Participants reported very strong intentions to use hearing aids (Median = 7.00 Q1 and Q3 = 6.67, 7.00, on a +1 to +7 scale) and high self-efficacy (Median = 7.00, Q1 and Q3 = 6.00, on a +1 to +7 scale) leaving little room for improvement. In contrast, participants reported moderate levels of post-motivational variables (action planning Median = 4.25, Q1 and Q3 = 1.13, 7.00 and coping planning Median = 2.75, Q1 and Q3 = 1.00, both measured on +1 to +7 scales) thereby showing significant scope for change. CONCLUSIONS: Future interventions to increase hearing aid use should focus on ensuring that patients' motivation is translated into action, rather than further trying to boost motivation.
Assuntos
Percepção Auditiva , Auxiliares de Audição , Transtornos da Audição/terapia , Motivação , Cooperação do Paciente , Pessoas com Deficiência Auditiva/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Audição , Transtornos da Audição/diagnóstico , Transtornos da Audição/fisiopatologia , Transtornos da Audição/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Pessoas com Deficiência Auditiva/psicologia , AutoeficáciaRESUMO
INTRODUCTION: Checkpoint inhibitors (CPI) are widely used across different tumour types in older cancer patients. The ELDERS study investigated primarily the safety of CPI in older patients, and secondarily its impact on health-related quality of life (HRQoL), comparing older and younger patients. Here we describe the results from its secondary aim. MATERIALS AND METHODS: This was an observational, mixed methods study, consisting of questionnaires and qualitative interviews. Patients completed the EORTC QLQ-C30 at baseline and at three-monthly reviews (up to four over the planned 12 months on study). RESULTS: One hundred and forty patients, 70 in each age cohort (older: ≥70 years of age, younger: <70 years of age), were recruited. Twenty-four patients, 12 in each age cohort, were interviewed. The mean baseline EORTC QLQ-C30 score was 65/100 for both cohorts combined, and the score for the full QLQ-C30 assessment was 78/100 and 75/100 for older and younger, respectively. The physical functioning score was the only subscale to change significantly between baseline and the first and second reviews (p = 0.03 and 0.04, respectively), resulting from some improvement in the mean score (from baseline) within the younger cohort and some decline within the older cohort. However, when focusing on each cohort separately, the change over time was not statistically significant for either. Two main themes from the interviews were 'expectations' (thoughts about treatment before commencing) and 'experience' (lived experience during treatment). DISCUSSION: Quantitatively, there was no difference in the effect of CPIs on HRQoL between the cohorts, although qualitative data from interviews suggested that there were some experiential differences. People in the older cohort were less likely to seek additional information about CPIs and were more likely to report side effects. In terms of both 'expectations' and 'experience,' the older cohort was a heterogenous group, highlighting that an individualised approach is needed when supporting this group. This study shows that older patients can be reassured that immunotherapy is unlikely to negatively impact their HRQoL more than younger patients, and it should be considered a viable treatment option.
Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Idoso , Neoplasias/tratamento farmacológico , Masculino , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Prospectivos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores EtáriosRESUMO
OBJECTIVES: A prospective cohort study to evaluate clinical effectiveness of the enhanced supportive care (ESC) service at a comprehensive cancer centre and to explore the impact of the service on patient and caregiver outcomes and experience. METHODS: Patients who received care under the ESC service and their caregivers were eligible. Consented patients (n=184) and caregivers (n=67) completed questionnaires at baseline, 4 weeks and 8 weeks post-ESC. Patient questionnaires assessed quality of life (QOL), symptoms, experience of ESC and health service use. Caregiver questionnaires included QOL and needs assessment. Selected patients (n=13) participated in qualitative interviews. Quantitative analysis explored differences in questionnaire responses over time (p<0.05). Qualitative data were analysed thematically. RESULTS: Patient quantitative data showed improvements in QOL (p=0.004 for European Quality of Life Questionnaire 5 dimensions (EQ5D) health index scores) and anxiety (p=0.006) at 4 weeks, reduction in some symptoms (pain p=0.02 at 4 weeks), improvement in self-efficacy, an increase in problems being addressed and a decrease in health service use (reduction in outpatient appointments). Qualitative findings suggested patients were generally satisfied with the ESC service but identified areas for improvement such as increased awareness of ESC and earlier referral. Fewer improvements were noted for caregivers; however, they did report a decrease in unmet needs. CONCLUSION: The ESC service had a positive impact on various patient-reported and caregiver-reported outcomes. There were also positive impacts on health service use. Increasing awareness of ESC and engaging patients at an earlier stage in the disease trajectory may further improve patient satisfaction and outcomes.
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Neoplasias , Qualidade de Vida , Humanos , Cuidadores , Estudos Prospectivos , Neoplasias/terapia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Given the physical health disparities associated with mental illness, targeted lifestyle interventions are required to reduce the risk of cardiometabolic disease. Integrating physical health early in mental health treatment among young people is essential for preventing physical comorbidities, reducing health disparities, managing medication side effects, and improving overall health outcomes. Digital technology is increasingly used to promote fitness, lifestyle, and physical health among the general population. However, using these interventions to promote physical health within mental health care requires a nuanced understanding of the factors that affect their adoption and implementation. OBJECTIVE: Using a qualitative design, we explored the attitudes of mental health care professionals (MHCPs) toward digital technologies for physical health with the goal of illuminating the opportunities, development, and implementation of the effective use of digital tools for promoting healthier lifestyles in mental health care. METHODS: Semistructured interviews were conducted with MHCPs (N=13) using reflexive thematic analysis to explore their experiences and perspectives on using digital health to promote physical health in youth mental health care settings. RESULTS: Three overarching themes from the qualitative analysis are reported: (1) motivation will affect implementation, (2) patients' readiness and capability, and (3) reallocation of staff roles and responsibilities. The subthemes within, and supporting quotes, are described. CONCLUSIONS: The use of digital means presents many opportunities for improving the provision of physical health interventions in mental health care settings. However, given the limited experience of many MHCPs with these technologies, formal training and additional support may improve the likelihood of implementation. Factors such as patient symptomatology, safety, and access to technology, as well as the readiness, acceptability, and capability of both MHCPs and patients to engage with digital tools, must also be considered. In addition, the potential benefits of data integration must be carefully weighed against the associated risks.
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Pessoal de Saúde , Transtornos Mentais , Pesquisa Qualitativa , Humanos , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Feminino , Masculino , Pessoal de Saúde/psicologia , Pessoal de Saúde/educação , Adulto , Adolescente , Atitude do Pessoal de Saúde , Promoção da Saúde/métodos , Estilo de Vida , Adulto JovemRESUMO
AIM: Recent years have seen innovation in 'mHealth' tools and health apps for the management/promotion of physical health and fitness across the general population. However, there is limited research on how this could be applied to mental healthcare. Therefore, we examined mental healthcare professionals' current uses and perceived roles of digital lifestyle interventions for promoting healthy lifestyles, physical health and fitness in youth mental healthcare. METHODS: A sequential, mixed-methods design was used, consisting of a quantitative online survey, followed by qualitative in-depth interviews. RESULTS: A total of 127 mental healthcare professionals participated in the online survey. Participants had limited mHealth experience, and the majority agreed that further training would be beneficial. Thirteen mental healthcare professionals were interviewed. Five themes were generated (i) digital technology's ability to enhance the physical healthcare; (ii) Conditions for the acceptability of apps; (iii) Limitations on staff capability and time; (iv) Motivation as the principal barrier; and (v) Practicalities around receiving lifestyle data. Systematic integration of data produced novel insights around: (i) staff involvement and needs; (ii) ideal focus and content of digital lifestyle interventions; and (iii) barriers towards implementation (including mental healthcare professionals own limited experience using digital lifestyle interventions, which aligned with the appeal of formal training). CONCLUSIONS: Overall, digital lifestyle interventions were positively received by mental healthcare professionals, particularly for health behaviour-tracking and mHealth support for exercise and nutrition. Practical suggestions for facilitating their uptake/implementation to improve availability of physical health interventions in mental healthcare are presented.
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Serviços de Saúde Mental , Telemedicina , Adolescente , Humanos , Tecnologia Digital , Motivação , Pessoal de SaúdeRESUMO
INTRODUCTION: Refractory or unexplained chronic cough (RUCC) is a common clinical problem with no effective diagnostic tools. The Sensations and Triggers Provoking Cough questionnaire (TOPIC) was developed to characterise cough in RUCC versus cough in other conditions. METHODS: Content analysis of participant interviews discussing the sensations and triggers of chronic cough informed TOPIC development. Participants with chronic cough completed the draft-TOPIC (a subset repeating 5-7 days later), St George's Respiratory Questionnaire (SGRQ), Cough Severity Diary (CSD) and Global Rating of Change Scale. The draft-TOPIC item list was reduced in hierarchical and Rasch analysis to refine the questionnaire to the TOPIC. RESULTS: 49 items describing the triggers and sensations of cough were generated from participant interviews (RUCC n=14, chronic obstructive pulmonary disease (COPD) n=11, interstitial lung disease (ILD) n=10, asthma n=11, bronchiectasis n=3, cystic fibrosis n=7). 140 participants (median age 60.0 (19.0-88.0), female 56.4%; RUCC n=39, ILD n=38, asthma n=45, COPD n=6, bronchiectasis n=12) completed draft-TOPIC, where items with poor 'fit' for RUCC were removed to create TOPIC (8 trigger items, 7 sensation items). Median TOPIC score was significantly higher in RUCC (37.0) vs ILD (24.5, p=0.009) and asthma (7.0, p<0.001), but not bronchiectasis (20.0, p=0.318) or COPD (18.5, p=0.238), likely due to small sample sizes. The Rasch model demonstrated excellent fit in RUCC (χ2=22.04, p=0.85; PSI=0.88); as expected. When all participant groups were included, fit was no longer demonstrated (χ2=66.43, p=0.0001, PSI=0.89) due to the increased heterogeneity (CI=0.077). TOPIC correlated positively with SGRQ (r=0.47, p<0.001) and CSD (r=0.63, p<0.001). The test-retest reliability of TOPIC (intraclass correlation coefficient) was excellent (r=0.90, p<0.001). CONCLUSIONS: High TOPIC scores in the RUCC patients suggest their cough is characterised by specific sensations and triggers. Validation of TOPIC in cough clinics may demonstrate value as an aid to identify features of RUCC versus cough in other conditions.
Assuntos
Tosse , Humanos , Tosse/etiologia , Tosse/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Inquéritos e Questionários , Doença Crônica , Adulto , Idoso de 80 Anos ou mais , Adulto Jovem , Sensação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Bronquiectasia/diagnóstico , Bronquiectasia/fisiopatologia , Asma/diagnóstico , Asma/complicações , Asma/fisiopatologia , Índice de Gravidade de Doença , Reprodutibilidade dos Testes , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/complicações , Fibrose Cística/complicações , Fibrose Cística/fisiopatologia , Tosse CrônicaRESUMO
To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel-Lindautumor suppressor (VHL). VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here we optimize and apply saturation genome editing to assay nearly all possible single-nucleotide variants (SNVs) across VHL's coding sequence. To delineate mechanisms, we quantify mRNA dosage effects and compare functional effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types and reveal new mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered clinically and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype-phenotype relationships across complete genes.
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Alelos , Carcinoma de Células Renais , Edição de Genes , Neoplasias Renais , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor Von Hippel-Lindau , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Humanos , Edição de Genes/métodos , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Linhagem Celular Tumoral , Predisposição Genética para Doença , MutaçãoRESUMO
BACKGROUND AND HYPOTHESIS: Previous studies show that people with severe mental illness (SMI) are at higher risk of COVID-19 mortality, however limited evidence exists regarding risk postvaccination. We investigated COVID-19 mortality among people with schizophrenia and other SMIs before, during and after the UK vaccine roll-out. STUDY DESIGN: Using the Greater Manchester (GM) Care Record to access routinely collected health data linked with death records, we plotted COVID-19 mortality rates over time in GM residents with schizophrenia/psychosis, bipolar disorder (BD), and/or recurrent major depressive disorder (MDD) from February 2020 to September 2021. Multivariable logistic regression was used to compare mortality risk (risk ratios; RRs) between people with SMI (N = 193 435) and age-sex matched controls (N = 773 734), adjusted for sociodemographic factors, preexisting comorbidities, and vaccination status. STUDY RESULTS: Mortality risks were significantly higher among people with SMI compared with matched controls, particularly among people with schizophrenia/psychosis (RR 3.18, CI 2.94-3.44) and/or BD (RR 2.69, CI 2.16-3.34). In adjusted models, the relative risk of COVID-19 mortality decreased, though remained significantly higher than matched controls for people with schizophrenia (RR 1.61, CI 1.45-1.79) and BD (RR 1.92, CI 1.47-2.50), but not recurrent MDD (RR 1.08, CI 0.99-1.17). People with SMI continued to show higher mortality rate ratios relative to controls throughout 2021, during vaccination roll-out. CONCLUSIONS: People with SMI, notably schizophrenia and BD, were at greater risk of COVID-19 mortality compared to matched controls. Despite population vaccination efforts that have prioritized people with SMI, disparities still remain in COVID-19 mortality for people with SMI.
Assuntos
COVID-19 , Transtorno Depressivo Maior , Transtornos Mentais , Humanos , Transtorno Depressivo Maior/epidemiologia , Estudos de Coortes , COVID-19/prevenção & controle , Transtornos Mentais/epidemiologia , Modelos Logísticos , VacinaçãoRESUMO
Background: The large health disparities among those diagnosed with schizophrenia urgently need to be addressed. These disparities are partially caused by adverse health behaviours such as smoking. Smoking cessation apps vary in efficacy across various populations, and there are concerns regarding the accessibility and usability of apps for people with schizophrenia. Objective: This review identifies and examines the feasibility of using apps for smoking cessation in people with schizophrenia. Methods: A non-systematic narrative literature review of smoking cessation apps for individuals with schizophrenia was performed. Results: Eight studies were included in this review. Conclusion: Smoking cessation apps can be acceptable and feasible, but may need to be tailored to the needs of people with schizophrenia. Key messages: (1) Smoking cessation apps could be acceptable and feasible for use in people with schizophrenia; (2) Lack of motivation was perceived as the main potential barrier with regard to people with schizophrenia engaging with smoking cessation apps; (3) In order to improve motivation of people diagnosed with schizophrenia, apps could include games, rewards, and/or social support; (4) Smoking cessation apps with a simple interface seem to be beneficial for this population; (5) Apps may need to be tailored to consider this population's mental health needs.
RESUMO
OBJECTIVES: The study aimed to explore patients' experiences of experimental cancer medicine (ECM) clinical trials. DESIGN: The study's design was qualitative. Two focus groups with patients were undertaken followed by semistructured interviews, to explore patients' experiences of ECM clinical trials. Interviews and focus groups were audiorecorded and transcribed verbatim. Data were analysed using thematic analysis. SETTING: A regional cancer centre (tertiary care) in North-West England. PARTICIPANTS: Twelve patients (aged 52-79) participated in one of the two focus groups and 22 patients (aged 42-83) participated in interviews. PRIMARY OUTCOME MEASURE: Patients' experiences of an ECM trial. RESULTS: Four main themes were identified from the analysis: decision making, information needs, the experience of trial participation and impact of trial participation. Subthemes are presented in the manuscript. CONCLUSION: To make fully informed decisions about trial participation, patients required the simplification of trial information and wanted more information about side effects, their response to trial treatment and the overall trial progress throughout the trial. Patients highlighted the need for improvement for the support provided to their family and friends.