RESUMO
BACKGROUND: Semaglutide is increasingly used in the management of type 2 diabetes mellitus and obesity. Ensuring the safety of this medication is crucial for its clinical use. This meta-analysis evaluates the safety profile of semaglutide across patient populations and treatment durations. METHODS: Randomized controlled trials assessing the safety of semaglutide vs. placebo, with specified treatment durations were identified. The primary outcome was occurrence of any cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, adverse events, gastrointestinal side effects, occurrence of hypoglycemia, and new-onset neoplasm. RESULTS: A total of 23 studies met the inclusion criteria with a combined sample size of 57,911 participants. The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups. CONCLUSION: Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity. It is generally well-tolerated, with a low incidence of adverse events. Clinicians should be aware of these findings and monitor patients accordingly. Further long-term studies are warranted to assess the safety of semaglutide in clinical practice.
RESUMO
BACKGROUND: People with multiple and persistent physical symptoms have impaired quality of life and poor experiences of health care. We aimed to evaluate the effectiveness of a community-based symptom-clinic intervention in people with multiple and persistent physical symptoms, hypothesising that this symptoms clinic plus usual care would be superior to usual care only. METHODS: The Multiple Symptoms Study 3 was a pragmatic, multicentre, parallel-group, individually randomised controlled trial conducted in 108 general practices in the UK National Health Service in four regions of England between Dec 6, 2018, and June 30, 2023. Participants were individually randomised (1:1) to the symptom-clinic intervention plus usual care or to usual care only via a computer-generated, pseudo-random list stratified by trial centre. Allocation was done by the trial statistician and concealed with a centralised, web-based randomisation system; masking participants was not possible due to the nature of the intervention. The symptom-clinic intervention was a sequence of up to four medical consultations that aimed to elicit a detailed clinical history, fully hear and validate the participant, offer rational explanations for symptoms, and assist the participant to develop ways of managing their symptoms; it was delivered by general practitioners with an extended role. The primary outcome was Patient Health Questionnaire-15 (PHQ-15) score 52 weeks after randomisation, analysed by intention to treat. The trial is registered on the ISRCTN registry (ISRCTN57050216). FINDINGS: 354 participants were randomly assigned; 178 (50%) were assigned to receive the community-based symptoms clinic plus usual care and 176 (50%) were assigned to receive usual care only. At the primary-outcome point of 52 weeks, PHQ-15 scores were 14·1 (SD 3·7) in the group receiving usual care and 12·2 (4·5) in the group receiving the intervention. The adjusted between-group difference of -1·82 (95% CI -2·67 to -0·97) was statistically significantly in favour of the intervention group (p<0·0001). There were 39 adverse events in the group receiving usual care and 36 adverse events in the group receiving the intervention. There were no statistically significant between-group differences in the proportion of participants who had non-serious adverse events (-0·03, 95% CI -0·11 to 0·05) or serious adverse events (0·02, -0·02 to 0·07). No serious adverse event was deemed to be related to the trial intervention. INTERPRETATION: Our symptom-clinic intervention, which focused on explaining persistent symptoms to participants in order to support self-management, led to sustained improvement in multiple and persistent physical symptoms. FUNDING: UK National Institute for Health and Care Research.
Assuntos
Qualidade de Vida , Humanos , Masculino , Feminino , Inglaterra , Pessoa de Meia-Idade , Adulto , Idoso , Clínicos Gerais , Medicina GeralRESUMO
Alpibectir (also known as BVL-GSK098 and GSK3729098) is a new chemical entity (NCE) with a novel mechanism for the treatment of tuberculosis. The disposition of alpibectir was determined in subjects from a first-time-in-human trial after a single oral dose of 40 mg and after 7 days repeat dosing at 30 mg. Here we present a combined approach of 19F-NMR (nuclear magnetic resonance), 1H-NMR, and high-resolution mass spectrometry (HRMS) to confidently determine the human metabolic fate of alpibectir. Utilizing multiple sites of fluorination in the molecule, it was possible to fractionate human urine and plasma to confidently detect and quantify the metabolite responses using 19F-NMR. Qualitative detection and structural characterization of F-containing NMR fractions were performed using complementary high-resolution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analyses to further add confidence to the metabolite responses in these fractions. Subsequent 1H-NMR then provided unequivocal standard-free structural confirmation for key metabolites, which would not be possible with conventional radioactivity detection and LC-MS/MS techniques. Alpibectir was shown to undergo extensive hydrolysis of the central amide moiety, where the resultant N-dealkylated amine and trifluorobutyric acid products were detected initially by unbiased 19F-NMR detection along with major downstream biotransformations to form a carbamoyl glucuronide conjugate and trifluoroacetic acid, respectively. Parallel UHPLC-MS/MS analyses provided confirmatory or additional structural characterization only where relevant. These concerted data allowed for the qualitative metabolic profile and quantitative determination of drug-related material (DRM) in urine and plasma, along with the percentage of dose excreted in urine, to be reported in a comprehensive, efficient, and data-led manner. SIGNIFICANCE STATEMENT: Combining the selectivity of 19F-NMR (nuclear magnetic resonance) for unfractionated samples as first-intent, data-led sample fractionation prior to 19F-NMR and structure-rich 1H-NMR detection, along with the sensitivity of high-resolution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), a novel alternative for time-efficient detection and quantification of drug-related material (DRM) in human without use of radiolabeled drug is reported. This allowed more complete data rationalization of human metabolism, permitting early risk assessment and progression of the development of antitubercular agent, alpibectir.
Assuntos
Espectroscopia de Ressonância Magnética , Humanos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Antituberculosos/farmacocinética , Antituberculosos/urina , Antituberculosos/metabolismo , Metabolômica/métodos , AdultoRESUMO
Progressive financing of health care can help advance the equity and financial protection goals of health systems. All countries' health systems are financed in part through private mechanisms, including out-of-pocket payments and voluntary health insurance. Yet little is known about how these financing schemes are structured, and the extent to which policies in place mitigate regressivity. This study identifies the potential policies to mitigate regressivity in private financing, builds two qualitative tools to comparatively assess regressivity of these two sources of revenue, and applies this tool to a selection of 29 high-income countries. It provides new evidence on the variations in policy approaches taken, and resultant regressivity, of private mechanisms of financing health care. These results inform a comprehensive assessment of progressivity of health systems financing, considering all revenue streams, that appears in this special section of the journal.
Assuntos
Atenção à Saúde , Gastos em Saúde , Humanos , Renda , Seguro Saúde , Instalações de Saúde , Financiamento da Assistência à SaúdeRESUMO
This paper contrasts the Irish experience of the 2008 economic crisis and the Covid-19 pandemic, and the health system responses to these shocks, from the perspective of health system leaders working across both time periods. Based on semi-structured interviews with seven senior national and international officials, the research presented here forms the qualitative component of RESTORE, a five-year research project examining health system resilience and reform, funded through the Health Research Board's Research Leader Award in Ireland. Findings indicate that the financial crisis deeply impacted the Irish health system in relation to infrastructure and capacity, service delivery and workforce. Due to these legacy issues, Ireland's health system was in a relatively weak position when faced with the Covid-19 pandemic but the system proved adaptive and innovative during this time. Furthermore, the pandemic proved to be a catalyst for positive change, providing opportunities for long-term reform, alongside an immediate response to the crisis. This was facilitated by increased funding, a devolution in decision-making structures and a political commitment to the health system. Exploring lessons from the Irish response to these crises provides a case study for developing appropriate policy responses around financing and resource allocation, fostering support for healthcare among political leaders and policy makers, and preparing for future shocks. Furthermore, examining these experiences facilitates understanding around the impact of each crisis on the health system, exploring options for addressing legacy issues and considering practical steps to improve health system performance.
Assuntos
COVID-19 , Pandemias , Humanos , Irlanda , Atenção à Saúde , PolíticasRESUMO
PURPOSE: Reports suggest pain is common in head and neck cancer (HNC). However, past studies are limited by small sample sizes and design and measurement heterogeneity. Using data from the Head and Neck 5000 longitudinal cohort, we investigated pain over a year post-diagnosis. We assessed: temporal trends; compared pain across HNC treatments, stages, sites and by HPV status; and identified subgroups of patients at increased risk of pain. METHODS: Sociodemographic and clinical data and patient-reported pain (measured by EORTC QLQ-C30 and QLQ-H&N35) were collected at baseline (pre-treatment), 4- and 12- months. Using mixed effects multivariable regression, we investigated time trends and identified associations between (i) clinically-important general pain and (ii) HN-specific pain and clinical, socio-economic, and demographic variables. RESULTS: 2,870 patients were included. At baseline, 40.9% had clinically-important general pain, rising to 47.6% at 4-months and declining to 35.5% at 12-months. HN-specific pain followed a similar pattern (mean score (sd): baseline 26.4 (25.10); 4-months. 28.9 (26.55); 12-months, 17.2 (19.83)). Across time, general and HN-specific pain levels were increased in: younger patients, smokers, and those with depression and comorbidities at baseline, and more advanced, oral cavity and HPV negative cancers. CONCLUSIONS: There is high prevalence of general pain in people living with HNC. We identified subgroups more often reporting general and HN-specific pain towards whom interventions could be targeted. IMPLICATIONS FOR CANCER SURVIVORS: Greater emphasis should be placed on identifying and treating pain in HNC. Systematic pain screening could help identify those who could benefit from an early pain management plan.
RESUMO
OBJECTIVES: Lack of evidence regarding safety and effectiveness at market entry is driving the need to consider adopting a lifecycle approach to evaluating medical devices, but it is unclear what lifecycle evaluation means. This research sought to explore the tacit meanings of "lifecycle" and "lifecycle evaluation" as embodied within evaluation models/frameworks used for medical devices. METHODS: Drawing on qualitative evidence synthesis methods and using an inductive approach, novel methods were developed to identify, appraise, analyze, and synthesize lifecycle evaluation models used for medical devices. Data was extracted (including purpose; audience; characterization; outputs; timing; and type of model) from key texts for coding, categorization, and comparison, exploring embodied meaning across four broad perspectives. RESULTS: Fifty-two models were included in the synthesis. They demonstrated significant heterogeneity of meaning, form, scope, timing, and purpose. The "lifecycle" may represent a single stage, a series of stages, a cycle of innovation, or a system. "Lifecycle evaluation" focuses on the overarching goal of the stakeholder group, and may use a single or repeated evaluation to inform decision-making regarding the adoption of health technologies (Healthcare), resource allocation (Policymaking), investment in new product development or marketing (Trade and Industry), or market regulation (Regulation). The adoption of a lifecycle approach by regulators has resulted in the deferral of evidence generation to the post-market phase. CONCLUSIONS: Using a "lifecycle evaluation" approach to inform reimbursement decision-making must not be allowed to further jeopardize evidence generation and patient safety by accepting inadequate evidence of safety and effectiveness for reimbursement decisions.
Assuntos
Equipamentos e Provisões , Formulação de Políticas , Equipamentos e Provisões/normasRESUMO
Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30%-80% experiencing it within 2 years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant leukemic stem cells (LSCs). These cells express genes related to stemness that are frequently difficult to eradicate and tend to survive standard treatments. Studies have demonstrated that by targeting the metabolic pathways of LSCs, it is possible to improve outcomes and extend the survival of those afflicted by leukemia. The overwhelming evidence suggests that lipid metabolism is reprogrammed in LSCs, leading to an increase in fatty acid uptake and de novo lipogenesis. Genes regulating this process also play a crucial role in therapy evasion. In this concise review, we summarize the lipid metabolism in normal hematopoietic cells, AML blast cells, and AML LSCs. We also compare the lipid metabolic signatures in de novo versus therapy-resistant AML blast and LSCs. We further discuss the metabolic switches, cellular crosstalk, potential targets, and inhibitors of lipid metabolism that could alleviate treatment resistance and relapse.
Assuntos
Leucemia Mieloide Aguda , Células-Tronco Neoplásicas , Humanos , Células-Tronco Neoplásicas/metabolismo , Leucemia Mieloide Aguda/patologia , Carcinogênese/patologia , Recidiva , Lipídeos/uso terapêuticoRESUMO
BACKGROUND: Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. METHODS: Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival. RESULTS: Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (>5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival. CONCLUSIONS: Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Saúde Bucal , Antissépticos Bucais , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasias de Cabeça e Pescoço/epidemiologiaRESUMO
A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Papillomavirus Humano 16 , Papillomavirus Humano , Neoplasias de Cabeça e Pescoço/diagnósticoRESUMO
Cancer-related fatigue (CRF) is a common side-effect of cancer and its treatments. For head and neck cancer (HNC), CRF may exacerbate the symptom burden and poor quality-of-life. Using data from the Head and Neck 5000 prospective clinical cohort, we investigated clinically important CRF over a year post-diagnosis, assessing temporal trends, CRF by HNC site and treatment received, and subgroups at higher risk of CRF. Recruitment was undertaken in 2011-2014. Socio-demographic and clinical data, and patient-reported CRF (EORTC QLQ-C30 fatigue subscale score ≥39 of a possible 100) were collected at baseline (pre-treatment) and 4- and 12- months post-baseline. Mixed-effects logistic multivariable regression was used to investigate time trends, compare cancer sites and treatment groups, and identify associations between clinical, socio-demographic and lifestyle variables and CRF. At baseline, 27.8% of 2847 patients scored in the range for clinically important CRF. This was 44.7% at 4 months and 29.6% at 12 months. In the multivariable model, after adjusting for time-point, the odds of having CRF over 12 months were significantly increased in females and current smokers; those with stage 3/4 disease, comorbidities and multimodal treatment; and those who had depression at baseline. The high prevalence of clinically important CRF indicates the need for additional interventions and supports for affected HNC patients. These findings also identified patient subgroups towards whom such interventions could be targeted.
RESUMO
BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung). METHODS: A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12â042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute). Linkage disequilibrium score regression estimated shared single-nucleotide variation (SNV-formerly SNP)-based heritability of rSTATacute in all patients and for each cancer type. RESULTS: Shared SNV-based heritability of STATacute among all cancer types was estimated at 10% (SE = 0.02) and was higher for prostate (17%, SE = 0.07), head and neck (27%, SE = 0.09), and breast (16%, SE = 0.09) cancers. We identified 130 suggestive associated SNVs with rSTATacute (5.0 × 10â8 < P < 1.0 × 10â5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size â0.17; P = 1.7 × 10â7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 × 10â6, P = .079 corrected) as the top gene set associated with rSTATacute among all patients. In silico gene expression analysis showed that the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed P = .004 corrected; sun exposed P = .026 corrected). CONCLUSIONS: There is shared SNV-based heritability for acute radiation-induced toxicity across and within individual cancer sites. Future meta-genome-wide association studies among large radiation therapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types.
Assuntos
Estudo de Associação Genômica Ampla , Neoplasias , Masculino , Humanos , Neoplasias/genética , Neoplasias/radioterapia , Mama , Predisposição Genética para DoençaRESUMO
BACKGROUND: People experiencing long-term homelessness face significant difficulties accessing appropriate healthcare at the right time and place. This study explores how and why healthcare performance management and funding arrangements contribute to healthcare accessibility or the lack thereof using long-term homeless adults as an example of a population experiencing social exclusion. METHODS: A realist evaluation was undertaken. Thirteen realist interviews were conducted after which data were transcribed, coded, and analysed. RESULTS: Fourteen CMOCs were created based on analysis of the data collected. These were then consolidated into four higher-level CMOCs. They show that health systems characterised by fragmentation are designed to meet their own needs above the needs of patients, and they rely on practitioners with a special interest and specialised services to fill the gaps in the system. Key contexts identified in the study include: health system fragmentation; health service fragmentation; bio-medical, one problem at a time model; responsive specialised services; unresponsive mainstream services; national strategy; short health system funding cycles; and short-term goals. CONCLUSION: When health services are fragmented and complex, the needs of socially excluded populations such as those experiencing homelessness are not met. Health systems focus on their own metrics and rely on separate actors such as independent NGOs to fill gaps when certain people are not accommodated in the mainstream health system. As a result, health systems lack a comprehensive understanding of the needs of all population groups and fail to plan adequately, which maintains fragmentation. Policy makers must set policy and plan health services based on a full understanding of needs of all population groups.
Assuntos
Acessibilidade aos Serviços de Saúde , Pessoas Mal Alojadas , Adulto , Humanos , Problemas Sociais , Serviços de Saúde , Instalações de SaúdeRESUMO
BACKGROUND: The Great Recession, following the 2008 financial crisis, led many governments to adopt programmes of austerity. This had a lasting impact on health system functionality, resources, staff (numbers, motivation and morale) and patient outcomes. This study aimed to understand how health system resilience was impacted and how this affects readiness for subsequent shocks. METHODS: A realist review identified legacies associated with austerity (proximal outcomes) and how these impact the distal outcome of health system resilience. EMBASE, CINAHL, MEDLINE, EconLit and Web of Science were searched (2007-May 2021), resulting in 1081 articles. Further theory-driven searches resulted in an additional 60 studies. Descriptive, inductive, deductive and retroductive realist analysis (utilising excel and Nvivo) aided the development of context-mechanism-outcome configurations (CMOCs), alongside stakeholder engagement to confirm or refute emerging results. Causal pathways, and the interplay between context and mechanisms that led to proximal and distal outcomes, were revealed. The refined CMOCs and policy recommendations focused primarily on workforce resilience. RESULTS: Five CMOCs demonstrated how austerity-driven policy decisions can impact health systems when driven by the priorities of external agents. This created a real or perceived shift away from the values and interests of health professionals, a distrust in decision-making processes and resistance to change. Their values were at odds with the realities of implementing such policy decisions within sustained restrictive working conditions (rationing of staff, consumables, treatment options). A diminished view of the profession and an inability to provide high-quality, equitable, and needs-led care, alongside stagnant or degraded working conditions, led to moral distress. This can forge legacies that may adversely impact resilience when faced with future shocks. CONCLUSION: This review reveals the importance of transparent, open communication, in addition to co-produced policies in order to avoid scenarios that can be detrimental to workforce and health system resilience.
Assuntos
Saúde Global , Pessoal de Saúde , Humanos , Programas Governamentais , Governo , Recursos HumanosRESUMO
This Viewpoint brings together insights from health system experts working in a range of settings. Our focus is on examining the state of the resilience field, including current thinking on definitions, conceptualisation, critiques, measurement, and capabilities. We highlight the analytical value of resilience, but also its risks, which include neglect of equity and of who is bearing the costs of resilience strategies. Resilience depends crucially on relationships between system actors and components, and-as amply shown during the COVID-19 pandemic-relationships with wider systems (eg, economic, political, and global governance structures). Resilience is therefore connected to power imbalances, which need to be addressed to enact the transformative strategies that are important in dealing with more persistent shocks and stressors, such as climate change. We discourage the framing of resilience as an outcome that can be measured; instead, we see it emerge from systemic resources and interactions, which have effects that can be measured. We propose a more complex categorisation of shocks than the common binary one of acute versus chronic, and outline some of the implications of this for resilience strategies. We encourage a shift in thinking from capacities towards capabilities-what actors could do in future with the necessary transformative strategies, which will need to encompass global, national, and local change. Finally, we highlight lessons emerging in relation to preparing for the next crisis, particularly in clarifying roles and avoiding fragmented governance.
Assuntos
COVID-19 , Humanos , Pandemias/prevenção & controle , Mudança Climática , Programas GovernamentaisRESUMO
Patients surviving head and neck cancer (HNC) suffer from high physical, psychological, and socioeconomic burdens. Achieving cancer-free survival with an optimal quality of life (QoL) is the primary goal for HNC patient management. So, maintaining lifelong surveillance is critical. An ambitious goal would be to carry this out through the advanced analysis of environmental, emotional, and behavioral data unobtrusively collected from mobile devices. The aim of this clinical trial is to reduce, with non-invasive tools (i.e., patients' mobile devices), the proportion of HNC survivors (i.e., having completed their curative treatment from 3 months to 10 years) experiencing a clinically relevant reduction in QoL during follow-up. The Big Data for Quality of Life (BD4QoL) study is an international, multicenter, randomized (2:1), open-label trial. The primary endpoint is a clinically relevant global health-related EORTC QLQ-C30 QoL deterioration (decrease ≥10 points) at any point during 24 months post-treatment follow-up. The target sample size is 420 patients. Patients will be randomized to be followed up using the BD4QoL platform or per standard clinical practice. The BD4QoL platform includes a set of services to allow patients monitoring and empowerment through two main tools: a mobile application installed on participants' smartphones, that includes a chatbot for e-coaching, and the Point of Care dashboard, to let the investigators manage patients data. In both arms, participants will be asked to complete QoL questionnaires at study entry and once every 6 months, and will undergo post-treatment follow up as per clinical practice. Patients randomized to the intervention arm (n=280) will receive access to the BD4QoL platform, those in the control arm (n=140) will not. Eligibility criteria include completing curative treatments for non-metastatic HNC and the use of an Android-based smartphone. Patients undergoing active treatments or with synchronous cancers are excluded. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT05315570).
RESUMO
Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.
Assuntos
Neoplasias de Cabeça e Pescoço , Proteínas Oncogênicas Virais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Papillomavirus Humano , Marcadores Genéticos , Fatores de Risco , Papillomavirus Humano 16/genética , Anticorpos Antivirais , Fatores de Transcrição/genética , Proteínas Oncogênicas Virais/genéticaRESUMO
Introduction: Child Safeguarding Services intervene in situations where a child is at risk of serious emotional or physical harm. The response will vary according to the level of risk, but in serious cases, a child may need to be removed from danger and cared for by foster parents either temporarily or permanently. The number of children being taken into care has increased markedly in recent years in the United Kingdom. Oxfordshire County Council (OCC) is implementing a new approach to the welfare of children (Family Solutions Plus; FSP) in which the focus is to support the whole family and ideally reduce the need for foster care.In this paper, we describe a proposed programme of evaluation to examine the impact of FSP on the time children are in contact with services, the nature of the support provided, experience of children and families, the experience of staff, and longer term outcomes for children, particularly whether they remain within the family or need to be cared for outside the home. Methods and analysis: A mixed methods approach will be taken in an observational retrospective study of children's social care services. Quantitative research will include descriptive analysis on data routinely collected by OCC, examining the effect on time spent in services, outcomes for children and how these outcomes are mediated by family characteristics and circumstances. Qualitative research will be carried out using individual interviews and focus groups with children, families and staff in the teams providing family safeguarding services to capture their experiences with the new model. Ethics and dissemination: This project has been registered with the OCC as a service evaluation. The qualitative studies will seek ethical approval from Oxford University Ethics Committee. A local data sharing agreement will govern the transfer of quantitative data. Results will be disseminated through newsletters, community forums, professional publications and conference presentations to national and international audiences.
RESUMO
INTRODUCTION: Persistent physical symptoms (which cannot be adequately attributed to physical disease) affect around 1 million people (2% of adults) in the UK. They affect patients' quality of life and account for at least one third of referrals from General Practitioners (GPs) to specialists. These referrals give patients little benefit but have a real cost to health services time and diagnostic resources. The symptoms clinic has been designed to help people make sense of persistent physical symptoms (especially if medical tests have been negative) and to reduce the impact of symptoms on daily life. METHODS AND ANALYSIS: This pragmatic, multicentre, randomised controlled trial will assess the clinical and cost-effectiveness of the symptoms clinic intervention plus usual care compared with usual care alone. Patients were identified through GP searches and mail-outs and recruited by the central research team. 354 participants were recruited and individually randomised (1:1). The primary outcome is the self-reported Physical Health Questionnaire-15 at 52 weeks postrandomisation. Secondary outcome measures include the EuroQol 5 dimension 5 level and healthcare resource use. Outcome measures will also be collected at 13 and 26 weeks postrandomisation. A process evaluation will be conducted including consultation content analysis and interviews with participants and key stakeholders. ETHICS AND DISSEMINATION: Ethics approval has been obtained via Greater Manchester Central Research Ethics Committee (Reference 18/NW/0422). The results of the trial will be submitted for publication in peer-reviewed journals, presented at relevant conferences and disseminated to trial participants and patient interest groups. TRIAL REGISTRATION NUMBER: ISRCTN57050216.