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Background: Cholangiocarcinomas (CCAs) are rare and aggressive malignant tumors of the biliary tract. Serotonin (5HT) has tumor-promoting effects in CCA while inhibition of 5HT synthesis can decrease tumor growth. Methods: In this retrospective study, we evaluated the expression of 5HT and tryptophane hydroxylase-1 (TPH-1) in tumor specimens from patients treated with cisplatin plus gemcitabine (CisGem). We included consecutive patients ≥18 years, with locally advanced unresectable, recurrent, or metastatic CCA who were treated with CisGem and had available archival tumor tissue for immunohistochemistry. Formalin-fixed paraffin (FFPE) sections were stained for 5HT and TPH-1. Specimens were evaluated for neuroendocrine features and tumor-infiltrating lymphocytes (TILs). Serum 5HT was measured. Results: We identified 23 patients fulfilling the inclusion criteria. 5HT expression was absent in almost all tumors examined. TPH-1 expression was neither associated with stage or primary tumor location nor predictive of response to CisGem. There was a trend for improved overall survival (OS) in patients whose tumors had high TPH-1 expression. The examined tumor specimens had no neuroendocrine features. Most sections had no TILs. There was a trend for worse OS in patients with high serum 5HT concentration. Conclusions: Tumor TPH-1 expression was not predictive of response to treatment. There was a trend for improved long-term outcomes in patients with high tumor TPH expression and lower serum 5HT concentration.
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Background: With a global dyslexia prevalence of at least 10%, significant numbers of students with dyslexia go undiagnosed and their symptoms unaddressed, but with timely intervention, 90% of dyslexic children can be educated in regular inclusive classrooms. Aim: This study aimed to estimate the prevalence of dyslexia among primary schoolchildren in government and private schools. Material and Methods: A cross-sectional study on 128 primary schoolchildren attending selected government and private schools in Western Maharashtra was conducted and evaluated using the Search tool, which is a standardized study tool for screening dyslexia. Microsoft Excel and MedCalc version 3.1 were used for data entry and analysis. The prevalence of dyslexia was estimated, and differences between groups were evaluated using appropriate tests. Results: Of the total sample size of 128 children, findings showed 10.9% of students as dyslexic, 9.3% as vulnerable, and the remaining 79.8% as non-dyslexic. Of 14 dyslexic children, 10 were found to be from government schools and the remaining four were from private schools. Conclusion: The high prevalence of dyslexia even in a small study sample size is a matter of concern and emphasizes the need for extensive research and initiatives, including awareness campaigns among teachers, parents, and school authorities, and the importance of detection of undiagnosed dyslexic children as early as possible and providing them with appropriate interventions.
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Breast cancer is more common on the left side than the right side. We aim to evaluate differences in clinicopathological and genomic characteristics based on laterality. We analyzed survival outcomes and clinical characteristics of 881,320 patients recorded by the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer Genome Atlas (TCGA) was used to explore genomic and clinical features from 1,062 patients. Gene expression data was used to quantitate cytolytic activity and hallmark gene-sets were used for gene set enrichment analysis. An institutional retrospective review was conducted on 155 patients treated with neoadjuvant chemotherapy (NACT). Patient characteristics were summarized by pathological complete response (pCR). Left sided tumors were found to be more prevalent than right sided tumors. No major clinicopathological differences were noted by laterality. Left sided breast cancer demonstrated poorer outcomes versus right sided tumors (HR 1.05, 95% CI 1.01-1.08; p = 0.011). Cell proliferation gene sets, including E2F Targets, G2M Checkpoint, Mitotic spindle, and MYC Targets, were enriched on the left side compared to the right. Left sided tumors had lower pCR rates versus right sided tumors (15.4% versus 29.9%, p = 0.036). Our findings suggest that left sided breast cancer is associated with aggressive biology and worse outcomes compared to right sided breast cancer.
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Neoplasias da Mama , Neoplasias Unilaterais da Mama , Biologia , Neoplasias da Mama/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Programa de SEER , Neoplasias Unilaterais da Mama/patologiaRESUMO
Therapeutic advancements in neuroendocrine tumors (NETs) have improved survival outcomes. This study aims to review the impact of the current therapeutics on health-related quality of life (HRQoL) in NET patients. A literature review was performed utilizing PubMed, The Cochrane Library, and EMBASE, using the keywords "Carcinoid", "Neuroendocrine tumor", "NET", "Quality of life", "Chemotherapy", "Chemoembolization", "Radiofrequency ablation", "Peptide receptor radionucleotide therapy", "PRRT", "Surgery", "Everolimus", "Octreotide", "Lanreotide", "Sunitinib", and "Somatostatin analog". Letters, editorials, narrative reviews, case reports, and studies not in English were excluded. Out of 2375 publications, 61 studies met our inclusion criteria. The commonly used instruments were EORTC QLQ-C30, FACT G, and EORTC- QLQ GI.NET-21. HRQoL was assessed in all pivotal trials that led to approvals of systemic therapies. All systemic therapies showed no worsening in HRQoL. The NETTER-1 study was the only study to show a statistically significant improvement in HRQoL in several domains. The trial examining sunitinib versus placebo in pancreatic NETs showed no change in QoL, except for worsening of diarrhea. In addition to clinical outcomes, patient-reported outcomes are a key element in making appropriate treatment decisions. HRQoL data should be readily provided to patients to assist in shared decision-making.
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BACKGROUND: Drowning is a public health problem globally. Despite substantial evidence on the effectiveness of life jackets, their use for drowning prevention has remained low. This study aims to understand the barriers and facilitators of life jacket use. METHODS: We searched four major electronic databases, contacted experts, hand-searched conference abstracts and screened reference lists to identify primary qualitative studies. We used the Critical Appraisal Skills Programme Checklist for quality appraisal and the PROGRESS Plus framework to understand equity issues. Thematic analysis was conducted. RESULTS: We retrieved 1153 records and finally included ten studies that met eligibility criteria. All except two studies were from high-income countries. Four key themes were identified. Firstly, life jacket use was shaped through complex interactions between lived experience and cultural norms which influenced the risk-perception of life jacket utility in preventing deaths. Secondly, the high cost of life jackets was almost always a barrier for its usage. Thirdly, adoption of laws and its subsequent enforcement was perceived to be an important facilitator for life jacket use. Lastly, design issues around comfort, fashion-sense, and shelf life influenced usage. CONCLUSION: The results of this qualitative evidence synthesis should be considered for health promotion, legal and policy interventions to promote the uptake of life jackets. There is a need for better understanding of perceptions and their role in the uptake of safety behaviours in different countries including the role of equity issues on the use of life jackets.
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Afogamento , Afogamento/prevenção & controle , Comportamentos Relacionados com a Saúde , Humanos , Políticas , Pesquisa QualitativaRESUMO
PURPOSE: Hematologic toxic effects of peptide receptor radionuclide therapy (PRRT) can be permanent. Patients with underlying clonal hematopoiesis (CH) may be more inclined to develop hematologic toxicity after PRRT. However, this association remains understudied. MATERIALS AND METHODS: We evaluated pre- and post-PRRT blood samples of patients with neuroendocrine tumors. After initial screening, 13 cases of interest were selected. Serial blood samples were obtained on 4 of 13 patients. Genomic DNA was analyzed using a 100-gene panel. A variant allele frequency cutoff of 1% was used to call CH. RESULT: Sixty-two percent of patients had CH at baseline. Persistent cytopenias were noted in 64% (7 of 11) of the patients. Serial sample analysis demonstrated that PRRT exposure resulted in clonal expansion of mutant DNA damage response genes (TP53, CHEK2, and PPM1D) and accompanying cytopenias in 75% (3 of 4) of the patients. One patient who had a normal baseline hemogram and developed persistent cytopenias after PRRT exposure showed expansion of mutant PPM1D (variant allele frequency increased to 20% after exposure from < 1% at baseline). In the other two patients, expansion of mutant TP53, CHEK2, and PPM1D clones was also noted along with cytopenia development. CONCLUSION: The shifts in hematopoietic clonal dynamics in our study were accompanied by emergence and persistence of cytopenias. These cytopenias likely represent premalignant state, as PPM1D-, CHEK2-, and TP53-mutant clones by themselves carry a high risk for transformation to therapy-related myeloid neoplasms. Future studies should consider CH screening and longitudinal monitoring as a key risk mitigation strategy for patients with neuroendocrine tumors receiving PRRT.
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Hematopoiese Clonal/genética , Hematopoese , Sistema Hematopoético , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/radioterapia , Proteína Fosfatase 2C/genética , Radioisótopos/efeitos adversos , Receptores de Peptídeos , Proteína Supressora de Tumor p53/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Radioisótopos/uso terapêutico , Radioterapia/efeitos adversosRESUMO
BACKGROUND: Living and environmental conditions in rural Bangladesh expose children to drowning. The Anchal programme protects children through crèche-based supervision in an enclosed space run by locally recruited carers. It is unclear under what conditions the programme best operates to maximise protection. We conducted a process evaluation of Anchal to determine enabling factors and challenges to implementation. METHODS: Quantitative programme data were analysed to calculate metrics including child participation and fidelity of implementation to defined processes. Qualitative data collection with programme participants and implementers provided insights into barriers and enablers of implementation. Analysis was guided by the UK Medical Research Council's process evaluation framework. RESULTS: Anchal operated 400 centres with an average of 22.2 children enrolled, as per target. However, daily attendance averaged lower than the 80% target. Children aged 1-2 years old, who are most at risk of drowning, were least likely to enrol and attend regularly due to low engagement with activities and parental concerns for safety. Greater distances and lower educational attainment in some regions reduced attendance and increased carer attrition. CONCLUSIONS: The Anchal programme met most programme delivery targets. However, programme success could be improved through increasing supervision, providing communication training for implementing staff, designing programmes for children aged 1-2 years old, encouraging community ownership and providing child pick-up services. These contextual solutions can be adapted to similar programmes operating through grassroots-level engagement and recruitment of community health workers, to maximise their effectiveness and sustainability.
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Afogamento , Bangladesh/epidemiologia , Cuidadores , Criança , Pré-Escolar , Afogamento/epidemiologia , Afogamento/prevenção & controle , Humanos , Lactente , Avaliação de Programas e Projetos de Saúde , População RuralRESUMO
Effective response to the COVID-19 pandemic is dependent on individual understanding of the disease and compliance to prevention measures. Early media depiction of health information about COVID-19 may influence public perceptions and behaviour. Media should ensure coverage is relevant, timely and actionable to encourage individuals to respond appropriately. India has been particularly affected by a large COVID-19 caseload. We analysed online reporting in India to assess how well the media represented health information about COVID-19 as per the World Health Organization's Strategic Risk Communications guidelines. This included media coverage of symptoms, transmission and prevention. We found that limited articles (18.8%) provided actionable suggestions to readers, including urging people to stay at home and social distance. Most articles were relevant as per WHO COVID-19 updates, accurately covering symptoms, risk factors for severe symptoms, transmission and prevention. However, 40% of media coverage of treatments options provided misleading information, such as suggesting plasma therapy or chloroquine, were effective. In addition, only 1.9% of articles included discussion of equity issues, where many prevention activities such as distancing are less applicable in lower-income households. Sixty-seven per cent of articles quoting sources of information quoted credible sources such as public health agencies and researchers. Media coverage also did not appear to reflect WHO updates in a timely manner, with most of the coverage preceding these updates. The findings show that Indian media should focus on actionable and relevant reporting that provides guidance for individual response. Media should also endeavour to report on evidence-based prevention and treatment options to avert the spread of misinformation.
The way media represents health information about COVID-19 may influence public understanding of the virus and behaviours they take to contain its spread. Therefore, media coverage should be accurate, timely and provide specific actions. India has been particularly affected by COVID-19. Based on the World Health Organization's Strategic Risk Communications guidelines, we analysed online reporting in India to assess how well the media represented COVID-19 health information. This included media coverage of symptoms, transmission and prevention. We found that very few articles provided direct suggestions to readers on prevention behaviours, such as staying at home. Most articles accurately covered symptoms, risk factors for severe symptoms, transmission and prevention. However, there was limited coverage of equity issues that affect low-income households, such as their ability to social distance or hand wash. In addition, treatment options not known to be effective received high coverage, such as plasma therapy. Only some articles included credible sources of information such as quoting public health agencies and researchers. Media coverage also usually preceding official updates from WHO, rather than waiting and responding to validated information. The Media should report on evidence-based prevention and treatment options to avert the spread of misinformation and encourage appropriate behaviours.
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COVID-19 , Mídias Sociais , COVID-19/prevenção & controle , Comunicação , Humanos , Pandemias/prevenção & controle , SARS-CoV-2RESUMO
Limited access to health care and the lack of robust data systems means non-fatal drownings are largely missed in low-and middle-income countries. We report morbidity among individuals who experienced non-fatal drowning in the Barishal Division, Bangladesh. A representative household survey was conducted in the Barishal Division in southern Bangladesh between September 2016 and February 2017, covering a population of 386,016. The burden of non-fatal drowning was assessed using the WHODAS 2.0 disability assessment tool, a generic assessment instrument for health and disability. A total of 5164 non-fatal drowning events occurred in the one year preceding the survey. Among these 18% were multiple events. From these, 4235 people were administered the WHODAS 2.0 questionnaire. Non-fatal drowning incidence rates were highest in children aged 1-4 years at 5810 per 100,000 population, and among males. Non-fatal drowning was associated with lower socio-economic status and larger family sizes. Few respondents (6.5%; 95% CI: 4.5-8.4%) reported some level of disability (WHODAS-12 score > 8). Incidence of non-fatal drowning is high in the population, however limited impact on morbidity was found. There is a need to develop tools and methodologies for reliable and comparable data for non-fatal drowning, especially to capture post-event disability in children.
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Afogamento , Bangladesh/epidemiologia , Criança , Afogamento/epidemiologia , Humanos , Incidência , Lactente , Masculino , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Media coverage of road traffic collisions (RTCs) may influence preventative action. India experiences some of the highest RTC mortality and morbidity rates globally, but advocacy and effective action to mitigate this has been limited. We conducted an analysis of Indian media in English to assess whether coverage met the WHO's Reporting on Road Safety guidelines for evidence-based reporting of RTCs. METHODS: English-language articles published online between March 2018 and February 2019 were assessed against the seven recommended story angles and seven recommended key elements in the WHO guidelines. RESULTS: 458 articles were included in the analysis. The most common story angle was descriptions of single collisions, which was not a WHO-recommended story angle. These included limited key elements such as use of human story or linking to road safety risks or evidence-based solutions. However, some articles did follow the WHO-recommended story angles, with 22.1% discussing specific road safety solutions and a further 6.3% discussing vulnerable groups. Almost all articles avoided the use of technical language, but only 2.0% explicitly stated that RTCs were preventable. More than half identified at least one evidence-based solution. Very few articles discussed economic or health impacts of RTCs, including the burden they present to the public health system. CONCLUSION: Indian media in English can improve reporting by focusing on human stories and documenting experiences of those injured in RTCs. Coverage should also focus more on evidence-based solutions, emphasising the systems approach which encourages government action rather than changes to individual behaviour.
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Acidentes de Trânsito , Comunicação , Acidentes de Trânsito/prevenção & controle , Humanos , ÍndiaRESUMO
Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic exocrine malignancy. Compared with the more common pancreatic ductal adenocarcinoma (PDAC), PACC is more common in younger White men, has earlier stages and a lower mean age (56 vs 70 years) at the time of presentation, and has a better prognosis. In addition to differences in demographic, histologic, and clinical characteristics, PACC has a genomic profile distinct from PDAC, with only rare mutations in TP53, KRAS, and p16 that are commonly found in PDAC. This case report presents a man aged 81 years who presented with a pancreatic body mass with peripancreatic lymph node enlargement. Biopsy of the mass showed acinar cell carcinoma. The patient underwent upfront surgical resection, followed by one cycle of adjuvant gemcitabine, with stoppage of therapy due to poor tolerance. Lower-dose gemcitabine was reintroduced after disease progression 6 months later. Nab-paclitaxel was added to gemcitabine after 6 cycles because of a continued increase in the size of peripancreatic lymph nodes. Combination chemotherapy was stopped after 4 cycles because of further disease progression with new liver metastasis. Molecular testing showed the presence of an SEL1L-NTRK1 fusion. Targeted therapy was started with the oral neurotrophic tropomyosin receptor kinase (NTRK) inhibitor larotrectinib at a dosage of 100 mg twice daily. At the time of writing, the patient has been on therapy for 13 months with an exceptional radiographic response and has not experienced any grade 3 adverse effects. To our knowledge, this is the first clinical report of an NTRK gene fusion in a patient with PACC. This case study highlights the significance of tumor molecular profiling in patients with pancreatic tumors, especially rare histologies.
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Carcinoma de Células Acinares , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Acinares/tratamento farmacológico , Carcinoma de Células Acinares/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Humanos , Masculino , Proteínas de Fusão Oncogênica/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas/genética , Receptor trkA/genéticaRESUMO
BACKGROUND: The Sundarbans in India is a rural, forested region where children are exposed to a high risk of drowning due to its waterlogged geography. Current data collection systems capture few drowning deaths in this region. METHODS: A community-based survey was conducted in the Sundarbans to determine the drowning mortality rate for children aged 1 to 4 years and 5 to 9 years. A community knowledge approach was used. Meetings were held with community residents and key informants to identify drowning deaths in the population. Identified deaths were verified by the child's household through a structured survey, inquiring on the circumstances around the drowning death. RESULTS: The drowning mortality rate for children aged 1 to 4 years was 243.8 per 100 000 children and for 5 to 9 years was 38.8 per 100 000 children. 58.0% of deaths were among children aged 1 to 2 years. No differences in rates between boys and girls were found. Most children drowned in ponds within 50 metres of their homes. Children were usually unaccompanied with their primary caretaker engaged in household work. A minority of children were treated by formal health providers. CONCLUSIONS: Drowning is a major cause of death among children in the Sundarbans, particularly those aged 1 to 4 years. Interventions keeping children in safe spaces away from water are urgently required. The results illustrate how routine data collection systems grossly underestimate drowning deaths, emphasising the importance of community-based surveys in capturing these deaths in rural low- and middle-income country contexts. The community knowledge approach provides a low-resource, validated methodology for this purpose.
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Afogamento , Criança , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , População Rural , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Community-based health programmes implemented in low-income and middle-income countries impact community gender norms and roles and relationships, which in turn affect individuals' health outcomes. Programmes should measure their effects on gender norms, roles and relationships in the communities in which they operate to respond to unexpected health consequences. We conducted a gender analysis on a drowning reduction programme in rural Bangladesh to identify its impacts on gendered roles and behaviours in the community. DESIGN: A mixed-method approach was used. Quantitative programme monitoring data were analysed to assess gender differences in participation and engagement. A qualitative approach using interviews, focus group discussions and observations with purposively selected programme implementing staff and participants aimed at finding explanations for quantitative findings and additional impacts of the programme on gender in the community. The analysis was conducted using Family Health International 360's Gender Integration Framework, which identifies both internal (norms) and external (behaviours) effects. RESULTS: Fewer girls (n=5030) participated in swimming classes than boys (n=6425) due to cultural restrictions and involvement in domestic work. Women were not hired in leadership roles in the implementing organisation due to lower transportation access and their perceived ability to conduct labour-intensive activities. However, communities become more accepting of local women's mobility and employment due to their engagement as swim instructors. Women swim instructors were more satisfied with the pay and part-time nature of the work as men were able to earn more elsewhere. Menstruation management was ignored as all supervisory staff were men. CONCLUSIONS: Systematised strategies are required to ensure equal participation of girls and enable equitable prevention outcomes. Within the implementing organisation, programmatic changes will support gender transformation, such as ensuring women's mobility and engagement in leadership roles. Strategies to combat perceptions that lower paying part time work is more suitable for women than men may be considered.
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Afogamento , Bangladesh/epidemiologia , Feminino , Grupos Focais , Equidade de Gênero , Humanos , Masculino , População RuralRESUMO
Drowning is a leading cause of child death in the coastal Sundarbans region of India due to the presence of open water, lack of supervision and poor infrastructure, but no prevention programs are currently implemented. The World Health Organization has identified interventions that may prevent child drowning in rural low-and middle-income country contexts, including the provision of home-based barriers, supervised childcare, swim and rescue training and first responder training. Child health programs should consider the local context and identify barriers for implementation. To ensure the sustainability of any drowning prevention programs implemented, we conducted a qualitative study to identify the considerations for the implementation of these interventions, and to understand how existing government programs could be leveraged. We also identified key stakeholders for involvement. We found that contextual factors such as geography, cultural beliefs around drowning, as well as skillsets of local people, would influence program delivery. Government programs such as accredited social health activists (ASHAs) and self-help groups could be leveraged for program implementation, while Anganwadi centres would require additional support due to poor resourcing. Gaining government permissions to change Anganwadi processes to provide childcare services may be challenging. The results showed that adapting drowning programs to the Sundarbans context presents unique challenges and program customisation.
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Neuroendocrine tumors (NETs) are a heterogenous group of tumors. While most NETs have excellent prognosis, certain subsets have aggressive biology and have limited treatment options. We explored the role of survivin in NET as a prognostic and potentially therapeutic marker. Tissue microarrays of 132 patients were stained for survivin using immunohistochemistry (IHC) and correlated with outcomes. Using genomic database, we then correlated survivin (BIRC5) mRNA expression with radiosensitivity index (RSI) in 52 samples of NET. Finally, we studied the effect of radiation on survivin expression in human cell lines and the impact of knock-down of BIRC5 on cell proliferation and radiation sensitivity. We found that survivin positivity by IHC correlated with a shorter survival (overall survival 8.5 years vs. 18.3 years, p < 0.001). There was a positive correlation between BIRC5 expression and RSI (r = 0.234, p < 0.0001). Radiation exposure increased BIRC5 gene expression in a human carcinoid cell line. Knockout of BIRC5 using siRNA reduced proliferation of neuroendocrine cells but did not increase radiation sensitivity. We conclude that survivin expression in NET correlates with an inferior survival and survivin expression in human carcinoid cell lines increases after exposure to ionizing radiation.
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BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death. It is a highly vascular tumour with multiple angiogenic factors, most importantly vascular endothelial growth factor (VEGF), involved in HCC progression. Tivozanib is an oral inhibitor of VEGFR-1/2/3 with promising activity against HCC in vivo. METHODS: We conducted a phase 1b/2 study of tivozanib in patients with advanced HCC. The safety, dosing, pharmacokinetics, pharmacodynamics, and preliminary antineoplastic efficacy of tivozanib were evaluated. RESULTS: Twenty-seven patients received at least one dose of tivozanib. Using a 3+3 design, the recommended phase 2 dose (RP2D) of tivozanib was determined to be 1 mg per os once daily, 21 days on-7 days off. The median progression-free and overall survival were 24 weeks and 9 months, respectively, for patients treated at RP2D. The overall response rate was 21%. Treatment was well tolerated. A significant decrease in soluble plasma VEGFR-2 was noted, assuring adequate target engagement. CONCLUSIONS: Although this study did not proceed to stage 2, there was an early efficacy signal with a very favourable toxicity profile. A phase 1/2 trial of tivozanib in combination with durvalumab is currently underway. TRIAL REGISTRATION: ClinicalTrials.gov NCT01835223, registered on 15 April 2013.
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Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/farmacologia , Quinolinas/farmacologia , Análise de Sobrevida , Adulto JovemRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy. Most of the patients of PDAC present at later stages of disease and have a five-year survival rate of less than 10%. About 5-10% PDAC cases are hereditary in nature and have DNA damage repair (DDR) mutations such as BRCA 1 and 2. Besides having implications on screening and prevention strategies, these mutations can confer sensitivity to platinum-based therapies and determine eligibility for poly(ADP-ribose) polymerase inhibitors (PARPi). In the presence of DDR mutations and PARPi, the cells are unable to utilize the error-free process of homologous recombination repair, leading to accumulation of double stranded DNA breaks and cell death eventually. Various PARPi are in clinical development in PDAC in different subgroup of patients as monotherapies and in combination with other therapeutics. This review would focus on the mechanism of action of PARPi, history of development in PDAC, resistance mechanisms and future directions.
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Cellulose from toilet paper is a significant fraction of particulate organics, which is recoverable. For the first time, comprehensive mapping and tracking the fate of cellulose across various unit processes at full-scale in two water resource recovery facilities located in North America and Europe was undertaken. The influent cellulose content accounted for approximately one-third of the total suspended solids (TSS). Although about 80% of the raw wastewater cellulose was removed in primary treatment, the type of primary treatment process (rotating belt filter [RBF] vs. primary clarification [PC]) had a significant impact on cellulose capture and diversion. The high cellulose content of the RBF sludge accounting for 35% of the TSS facilitates cellulose recovery. For the North American plant, with a conventional activated sludge process (SRT of 6-7 days, preceded by PC), cellulose biodegradation efficiencies of 70%-90% of the PC effluent were observed in summer and winter. For the European plant, with a modified University of Cape Town process (SRT of 14 days, without primary treatment in train 2, or preceded by RBF in train 1), comparable cellulose biodegradation efficiencies were also observed. Results from laboratory SBRs indicated that cellulose biodegradation efficiency at room temperature was 86% of the influent cellulose. PRACTITIONER POINTS: Cellulose fate was tracked across two different WWTPs in two different geographies. Cellulose in the influent wastewater accounted for 1/3 of the total suspended solids. Primary treatments were able to capture more than 80% of the influent cellulose. Cellulose was biodegraded in secondary treatment, resulting an effluent of 2-3 mg/L.
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Eliminação de Resíduos Líquidos , Poluentes Químicos da Água , Celulose , Esgotos , Águas Residuárias , Recursos Hídricos , Abastecimento de ÁguaRESUMO
Living and geographical conditions in Bangladesh expose children to a high risk of drowning. Two programs operating in the Barishal Division of Bangladesh aim to reduce drowning risk through the provision of crèches (Anchal) and swim and rescue classes (SwimSafe). Anchal provides a safe environment with early childhood education to children aged 1â»5 years old, while SwimSafe teaches children aged 6â»10 years old basic swimming and rescue skills. Despite evidence for their effectiveness, it is unclear under which conditions these programs best operate. This protocol describes a project that seeks to conduct a process evaluation and gender analysis to identify implementation inefficiencies and contextual considerations for improved sustainability of the programs. A mixed- method approach using both qualitative and quantitative data will be used. Quantitative program data will be analysed to measure program utilisation, delivery and reach, while qualitative data will be collected via key informant in-depth interviews (IDIs), focus group discussions (FGDs) and observations. The process evaluation of the Anchal and SwimSafe programs provides an opportunity for implementers to identify practical strategies to improve program delivery and improve contextual adaptability of these programs. Furthermore, the findings may provide guidance to other implementers aiming to deliver community-based programs in rural lower-middle income contexts.