RESUMO
This study assessed the psychological predictors of attitudes toward the return of germline genomic sequencing results in cancer patients and their biological relatives with a likely genetic basis for their cancer diagnosis, who completed a questionnaire prior to undergoing genomic sequencing. Of 602 probands and relatives, 94% of probands and 89% of relatives thought people would like to be informed about single-gene conditions for which there is prevention or treatment. Amongst relatives, this view was associated with higher perceived susceptibility and self-efficacy. Probands (66%) and relatives (59%) thought people would be interested in learning about single-gene conditions for which there is no prevention or treatment. Amongst probands, this view was associated with lower tolerance of uncertainty and amongst relatives with higher self-efficacy. Probands (92%) and relatives (90%) thought people would like to be informed about polygenic conditions that can have a major impact on health. Amongst probands this view was associated with lower perceived susceptibility of cancer recurrence, and amongst relatives, with higher perceived susceptibility and self-efficacy. Probands (86%) and relatives (86%) thought that people would like to be informed about polygenic conditions that can have a lower impact on health, and this view was associated with a lower perceived susceptibility of recurrence amongst probands. In conclusion, these findings show that individuals' attitudes about the return of results depend on the perceived utility of different types of tests. Therefore, individuals need to gain a clear understanding of test utility, and appropriate consent processes are required to achieve informed choices.
Assuntos
Neoplasias , Atitude , Família , Genômica/métodos , Humanos , Neoplasias/genética , Inquéritos e QuestionáriosRESUMO
Germline genome sequencing (GS) holds great promise for cancer prevention by identifying cancer risk and guiding prevention strategies, however research evidence is mixed regarding patient preferences for receiving GS results. The aim of this study was to discern preferences for return of results by cancer patients who have actually undergone GS. We conducted a mixed methods study with a cohort of cancer probands (n = 335) and their genetic relatives (n = 199) undergoing GS in a research setting. Both groups completed surveys when giving consent. A subset of participants (n = 40) completed semi-structured interviews. A significantly higher percentage of probands thought people would like to be informed about genetic conditions for which there is prevention or treatment that can change cancer risk compared to conditions for which there is no prevention or treatment (93% [311] versus 65% [216]; p < 0.001). Similar results were obtained for relatives (91% [180] versus 61% [121]; p < 0.001). Themes identified in the analysis of interviews were: (1) Recognised benefits of GS, (2) Balancing benefits with risks, (3) Uncertain results are perceived as unhelpful and (4) Competing obligations. While utility was an important discriminator in what was seen as valuable for this cohort, there was a variety of responses. In view of varied participant preferences regarding return of results, it is important to ensure patient understanding of test validity and identify individual choices at the time of consent to GS. The nature and value of the information, and a contextual understanding of researcher obligations should guide result return.
Assuntos
Neoplasias , Sequência de Bases , Células Germinativas , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Preferência do Paciente , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Comprehensive tumor genomic profiling (CTGP) is increasingly used to personalize treatments, providing hope, but potentially disappointment, for patients. We explored psychological outcomes in patients with advanced, incurable cancer, after receiving CTGP results. METHODS: Participants with advanced, incurable cancer (n = 560, mean age 56, 43% university educated) in this longitudinal substudy of the Molecular Screening and Therapeutics Program (MoST), completed questionnaires before and after receiving CGP results. MoST participants, recruited from Australian oncology clinics, undergo CTGP, and if there are actionable findings, are offered treatment in a related therapeutic trial if available. RESULTS: Patients who received actionable results, (n = 356, 64%) had lower gene-related distress (MICRA) (p < 0.001) and Impact of Events scores (p = 0.039) than patients with non-actionable results. Those with actionable results offered ensured access to tailored treatment (n = 151) reported lower anxiety (p = 0.002) and depressive symptoms (p = 0.01) and greater hope (p = 0.002) than those not offered. Positive attitudes towards uncertainty and higher self-efficacy for coping with results were associated with lower psychological distress and uncertainty, and higher hope and satisfaction with the decision to have CTGP (ps=0.001-0.047). Those with higher knowledge reported greater anxiety (p = 0.034). CONCLUSION: Receiving a non-actionable CTGP result, or an actionable result without ensured access to treatment, may cause increased distress in advanced cancer patients. Coping style was also associated with distress. PRACTICE IMPLICATIONS: Pre-testing assessment and counseling addressing attitudes toward uncertainty and self-efficacy, and post-CTGP result support for patients receiving a non-actionable result or who receive an actionable results without ensured access to treatment, may benefit patients.
Assuntos
Genômica , Neoplasias , Ansiedade , Austrália , Genômica/métodos , Humanos , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/psicologia , Neoplasias/terapia , IncertezaRESUMO
This study assessed the psychological predictors of preferences for return of comprehensive tumor genomic profiling (CTGP) results in patients with advanced cancers, enrolled in the Molecular Screening and Therapeutics Program. Patients completed a questionnaire prior to undergoing CTGP. Of the 1434 who completed a questionnaire, 96% would like to receive results that can guide treatment for their cancer, and preference for receiving this type of result was associated with lower tolerance of uncertainty. Sixty-four percent would like to receive results that cannot guide treatment, and lower tolerance of uncertainty, self-efficacy, and perceived importance were associated with this preference. Fifty-nine percent would like to receive variants of unknown significance, which was associated with lower tolerance of uncertainty, higher self-efficacy, and perceived importance. Eighty-six percent wanted to receive germline results that could inform family risk. This was associated with higher self-efficacy, perceived importance, and perceived susceptibility. Although most patients wanted to receive all types of results, given the differing patient preferences regarding the return of results depending on the utility of the different types of results, it appears critical to safeguard patient understanding of result utility to achieve informed patient choices. This should be accompanied by appropriate consent processes.
Assuntos
Neoplasias , Preferência do Paciente , Genoma , Genômica/métodos , Humanos , Neoplasias/patologia , Preferência do Paciente/psicologia , Inquéritos e QuestionáriosRESUMO
AIM: Children living in families impacted by parental mental illness are at increased risk of adverse mental and physical health outcomes compared with children living in families unaffected by mental illness. Considered to be a hard-to reach group, it is likely that there are unique barriers for these young people in seeking help for their difficulties. This systematized review synthesizes what is currently known about help-seeking barriers, facilitators and interventions for young people affected by parental mental illness. METHODS: Three databases were searched, yielding 2556 results and three studies were identified through other sources. Studies were screened on title and abstract review and were excluded if they were published before 2005 or if they did not include the perspectives of young people. At a second stage, full-text articles were screened based on the inclusion criteria. Eleven studies were included for data extraction and quality appraisal. RESULTS: Qualitative and quantitative data synthesis revealed three significant barriers (i) stigma, (ii) family communication and (iii) lack of belonging and shared experience, three key facilitators (i) individual characteristics, (ii) group identification and (iii) anonymity and three primary components of therapeutic interventions (i) psychoeducation, (ii) connection with peers and (iii) accessibility. CONCLUSIONS: It was found that stigma towards mental illness is highly salient amongst young people impacted by parental mental illness and has unique effects on their patterns of help-seeking. Help-seeking research amongst this group is still emerging, with a need for greater clarity in operationalisation of help-seeking constructs and more robust methodological designs.
Assuntos
Transtornos Mentais , Adolescente , Criança , Humanos , Transtornos Mentais/terapia , Pais , Sistemas de Apoio Psicossocial , Estigma SocialRESUMO
OBJECTIVES: Germline genome sequencing (GS) is becoming mainstream in cancer diagnosis and risk management. Identifying knowledge gaps and determinants of health behavior change intentions will enable effective targeting of educational and management strategies to translate genomic findings into improved cancer outcomes. METHODS: Probands diagnosed with cancer of likely genetic origin that consented to but not yet undergone GS, and their biological relatives, completed a cross-sectional questionnaire assessing GS knowledge and hypothetical intention to change behaviors. RESULTS: Probands (n = 348; 57% university educated) and relatives (n = 213; 38% university educated) had moderate GS knowledge levels, with greater knowledge associated with higher education. Both populations reported high behavioral change intentions, significantly associated with being female (p = 0.01) and greater perceived importance of GS (p < 0.001), and for probands: being from English-speaking households (p = 0.003), higher socio-economic status (p = 0.01) and greater self-efficacy (p = 0.02). CONCLUSIONS: Increasing GS knowledge will enable realistic participant expectations surrounding germline GS. Actual behavior change should be monitored to determine whether increased cancer risk knowledge results in altered cancer-related behavior and ultimately, cancer outcomes. PRACTICE IMPLICATIONS: Educational resources should target specific populations to ensure informed decision-making and expectation management. Support tools facilitating and maintaining behavioral change may be needed to achieve improved cancer patient outcomes.
Assuntos
Intenção , Neoplasias , Estudos Transversais , Feminino , Genômica , Células Germinativas , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Neoplasias/genética , Neoplasias/terapia , Inquéritos e QuestionáriosRESUMO
Genomic Sequencing (GS) to identify high cancer risk will soon enter clinical practice at significant cost to the health system. This study aimed to quantify perceived value of GS to Australian cancer patients and their first-degree relatives participating in a genomic sequencing study, and factors associated with value. Participants were recruited upon consent to the genomics study. Eligible participants (with cancer of likely genetic etiology, or a first-degree relative) completed a questionnaire prior to GS. Willingness to pay was assessed via hypothetical trade-off scenarios of actionable result return rates of 1%, 10%, 20%, 30%, 40% or 50%. Of 348 probands and 213 relatives (92% and 93% response rate), 81% would consistently have GS for as little as a 1% actionable return rate. Participants would pay a median of $1,000 for return rates of at least 20% (probands) or 30% (relatives), and $300 for lower return rates. Probands with common cancers and negative attitudes to uncertainty were more likely to have GS; those with higher education were more willing to pay $1,000 and $3,000 for lower return rates. This study found high interest in, but lower willingness to pay for GS in cancer patients and their first-degree relatives, possibly due to inability to pay. Further research is needed to improve our understanding of how individuals in different risk circumstances, trade-off the risks, harms, and benefits of GS.
Assuntos
Genômica , Neoplasias , Austrália , Humanos , Neoplasias/genética , Inquéritos e Questionários , Sequenciamento Completo do GenomaRESUMO
PURPOSE: Fear of cancer recurrence/occurrence (FCR/O) is prevalent and associated with poorer psychological outcomes but can also motivate individuals to pursue genomic information about cancer risk. Guided by Protection Motivation Theory, this study investigated FCR/O prevalence and associated factors among probands previously diagnosed with a cancer of likely heritable origin, and their relatives, who had agreed to have germline genome sequencing. METHODS: Three hundred and forty-eight probands and 167 relatives completed the Concerns about Recurrence Questionnaire (adapted for occurrence for some relatives) within 1 month of agreeing to undertake genome sequencing. Linear regressions investigated demographic, disease, attitude and behavioral associations with FCR/O. RESULTS: Probands demonstrated greater FCR compared to relatives. In probands, greater FCR was associated with being female, non-English speaking at home, less time since diagnosis, greater intention to change behavior if gene variant found, lower perceived ability to cope with results, higher perceived susceptibility to having a recurrence, and more negative attitudes towards uncertainty. For relatives with cancer, greater FCR was associated with being male, greater intention to change behavior if a gene variant found, and higher perceived susceptibility to recurrence. In relatives without cancer, greater FCO was associated with not having had genetic testing prior to this study, lower perceived ability to cope with results, and higher perceived susceptibility to developing cancer. CONCLUSION: Current findings on FCR/O prevalence and associated demographic and attitudinal variables in those who pursue genomic risk information might be used to target interventions that can prevent adverse psychological outcomes in vulnerable patients.
Assuntos
Recidiva Local de Neoplasia , Transtornos Fóbicos , Adaptação Psicológica , Medo , Feminino , Células Germinativas , Humanos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genéticaRESUMO
OBJECTIVES: Single-gene testing is associated with psycho-social challenges for cancer patients. Genomic testing may amplify these. The aim of this study was to understand patients' motivations and barriers to pursue cancer genomic testing, to enable healthcare providers to support their patients throughout the testing process and interpretation of test results. METHODS: Five databases were searched for original peer reviewed research articles published between January 2001 and September 2018 addressing motivation for genomic cancer testing. QualSyst was used to assess quality. RESULTS: 182 studies were identified and 17 were included for review. Studies were heterogenous. Both somatic and germline testing were included, and 14 studies used hypothetical scenarios. 3249 participants were analyzed, aged 18 to 94. Most were female and white. The most common diagnoses were breast, ovarian, lung and colorectal cancer. Interest in testing was high. Motivations included ability to predict cancer risk, inform disease management, benefit families, and understand cancer. Barriers included concerns about cost, privacy/confidentiality, clinical utility, and psychological harm. CONCLUSIONS: Despite concerns, consumers are interested in cancer genomic testing if it can provide actionable results for themselves and their families. PRACTICE IMPLICATIONS: Providers must manage understanding and expectations of testing and translate genetic information into health-promoting behaviours.
Assuntos
Motivação , Neoplasias , Feminino , Testes Genéticos , Genômica , Comportamentos Relacionados com a Saúde , Humanos , Neoplasias/diagnóstico , Neoplasias/genéticaRESUMO
OBJECTIVE: This study aimed to discern preferences for receiving somatic molecular profiling (MP) results in cancer patients who have given consent to undergo testing. METHODS: We conducted a mixed-methods study to explore patients' views on which MP results they would like to receive and why. Advanced cancer patients (n = 1299) completed questionnaires after giving consent to participate in a parent genomics study and undergoing MP. A subset of patients (n = 20) participated in qualitative interviews. RESULTS: Almost all (96%) participants were interested in receiving results which would direct cancer treatment (ie, were actionable). A smaller majority wanted to access results which were not actionable (64%) or were variants of unknown significance (60%). Most (86%) were interested in finding out about germline findings, though not as a priority. Themes identified in interview data were: (a) Cancer is the focus; (b) Trust in clinicians; and (c) Respect for a right not to know. CONCLUSIONS: The majority of advanced cancer patients undergoing MP prioritised results which would lead to treatment options. They trusted their oncologists to help them navigate the results return process. While there was interest in knowing about other results, this was a lesser priority. Nevertheless, given high levels of interest in receiving all results, ethical aspects of not providing uninformative results requires further research, including a consideration of patient rationales for desiring this information and what health professionals can and should do to support patients in the absence of meaningful information being available.
Assuntos
Bioética , Pessoal de Saúde/psicologia , Neoplasias/patologia , Patologia Molecular/estatística & dados numéricos , Preferência do Paciente/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Patologia Molecular/ética , Medicina de Precisão , Pesquisa Qualitativa , Inquéritos e Questionários , ConfiançaRESUMO
Importance: Use of tumor molecular profiling (MP) is entering routine clinical practice; however, little is known about how much and why patients value MP. Objective: To examine the perceived value of MP to patients with advanced cancer and factors associated with perceived value. Design, Setting, and Participants: A cross-sectional survey that included willingness-to-pay trade-off scenarios was administered to participants after consent and before MP. A total of 777 participants (94% response rate) were recruited from the Molecular Screening and Therapeutics Program. Eligible patients had advanced solid cancers of any histologic type, were receiving or had completed their last line of effective therapy, had an Eastern Cooperative Oncology Group Performance Status 0 to 3, and had sufficient accessible tissue for MP. The participants were recruited between October 24, 2017, and March 12, 2019, and data analysis was conducted from March 13 to April 14, 2019. Main Outcomes and Measures: Willingness to pay for MP was assessed via hypothetical trade-off scenarios varying in the actionable return rate (1%, 20%, or 40%) and cost (A$0, A$300 [US$210], A$1000 [US $700], A$3000 [US $2100], or A$10â¯000 [US $7000]). Ordinal regressions were used to explore factors associated with willingness to have and pay for MP. Results: Of 777 participants (405 women [52%]; mean [SD] age, 55.47 [14.26] years), 689 patients (89%) would have MP for as little as a 1% actionable return rate. Fifty-six patients (7%) would require at least a 20% return rate and 11 patients (1%) would require at least a 40% return rate. Fifteen patients (2%) consistently chose not to have the test; 6 participants (0.8%) had missing values on this item. Participants were willing to pay a median of A$1000 if the actionable return rate was 1% and A$3000 for an actionable return rate of 20% to 40%. Of 762 individuals who agreed to testing, 482 patients (64%) were consistently unwilling to pay A$10â¯000, regardless of the actionable return rate. Patients born in Australia or New Zealand were more likely to want MP (eg, participants born in South Asia had an ordered odds for the tipping point of 7.74 [95% CI, 1.67-36.05; P = .009] times higher than Australian- and/or New Zealand-born participants). Patients born in Australia or New Zealand were also more willing to pay A$1000 or A$3000 (eg, participants born in Western Europe had an ordered odds for the tipping point for paying A$1000 of 1.74 [95% CI, 1.01-3.00; P = .048] times higher than Australian- and/or New Zealand-born participants). People with a medical- or science-related occupation and with more negative attitudes toward uncertainty were more likely to pay A$10 000 (eg, A$10 000 tipping point-ordered odds of participants with a medical- or science-related occupation was 0.49 [95% CI, 0.7-0.87; P = .02] times that of participants without a medical- or science-related occupation). Conclusions and Relevance: This study found apparent high interest in but lower willingness to pay for MP among patients with advanced cancer. Ability to pay may limit access to MP. Ongoing societal debate is required to establish the value of MP and whether subsidization is needed to ensure equity of access.
Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/economia , Neoplasias/genética , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Transversais , Feminino , Financiamento Pessoal , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologiaRESUMO
Limited research has indicated that despite their overwhelming interest in tumor molecular profiling (MP),1 cancer patients have poor knowledge about MP. The current study aimed to investigate demographic and psychological predictors of knowledge and perceived importance of MP in an advanced cancer patient cohort. Eligible participants had advanced solid cancers of any histological type with sufficient accessible tissue for MP and were enrolled in the Molecular Screening and Therapeutics (MoST) Program. A questionnaire was completed by 1074 participants (91% response rate) after consent, prior to undergoing MP. Overall, participants had poor to moderate knowledge of MP, yet perceived MP to have high importance. Higher education, speaking English at home, and greater satisfaction with the decision to undergo MP were associated with higher knowledge scores. More negative attitudes towards uncertainty, greater self-efficacy to cope with results, and lower perceived likelihood of cancer progression were associated with greater perceived importance of MP. Less educated participants and those who do not speak English at home will need clear explanations, visual aids and ample opportunity to ask questions about MP at the time of their decision-making. Clinicians also need to consider psychological factors relevant to patients' decision to pursue MP. Given the increased awareness of and demand for cancer genomic information and the rapidly changing nature of the actionability of MP, these findings will help inform an important ongoing debate on how to facilitate ethical and informed consent and manage patient expectations about personalized treatments.
RESUMO
Implementation of any new medical test, including germline genome sequencing (GS) to inform cancer risk, should take place only when a test is effective, ethically justifiable and acceptable to a population. Little empirical evidence exists on patient views regarding GS for cancer risk. The aim of this study was to elicit opinions on who should be offered GS and who should pay for it. Participants with a probable genetic basis for their cancer (n = 335) and blood relatives (n = 199) were recruited to undergo GS and invited to complete questionnaires at baseline. A subset (n = 40) also participated in qualitative interviews about their views regarding access to GS to detect cancer risk. Our response rate was 92% for questionnaires and 100% for interviews. Participants expressed high enthusiasm overall for access to GS for those with a family history of cancer and anyone who requested testing, but enthusiasm was lower for universal access, if opting out was possible and finances not an issue. Rationales for these views reflected maximising the sound use of resources. Challenges to introducing community screening via GS to limit cancer burden were raised, including the current limits of science and individual ability to cope with uncertain results. Participants undergoing GS supported cancer risk testing for those with a family history of cancer but were concerned about the challenges of designing and implementing a population-based GS cancer-screening program.
Assuntos
Detecção Precoce de Câncer/ética , Neoplasias/genética , Sequenciamento Completo do Genoma/ética , Adolescente , Adulto , Criança , Pré-Escolar , Família/psicologia , Feminino , Células Germinativas/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias/diagnóstico , Pacientes/psicologia , Inquéritos e Questionários , Sequenciamento Completo do Genoma/tendências , Adulto JovemRESUMO
Bumblebees (Bombus spp.) rely on an abundant and diverse selection of floral resources to meet their nutritional requirements. In farmed landscapes, mass-flowering crops can provide an important forage resource for bumblebees, with increased visitation from bumblebees into mass-flowering crops having an additional benefit to growers who require pollination services. This study explores the mutualistic relationship between Bombus terrestris L. (buff-tailed bumblebee), a common species in European farmland, and the mass-flowering crop courgette (Cucurbita pepo L.) to see how effective B. terrestris is at pollinating courgette and in return how courgette may affect B. terrestris colony dynamics. By combining empirical data on nectar and pollen availability with model simulations using the novel bumblebee model Bumble-BEEHAVE, we were able to quantify and simulate for the first time, the importance of courgette as a mass-flowering forage resource for bumblebees. Courgette provides vast quantities of nectar to ensure a high visitation rate, which combined with abundant pollen grains, enables B. terrestris to have a high pollination potential. While B. terrestris showed a strong fidelity to courgette flowers for nectar, courgette pollen was not found in any pollen loads from returning foragers. Nonetheless, model simulations showed that early season courgette (nectar) increased the number of hibernating queens, colonies, and adult workers in the modeled landscapes. Synthesis and applications. Courgette has the potential to improve bumblebee population dynamics; however, the lack of evidence of the bees collecting courgette pollen in this study suggests that bees can only benefit from this transient nectar source if alternative floral resources, particularly pollen, are also available to fulfill bees' nutritional requirements in space and time. Therefore, providing additional forage resources could simultaneously improve pollination services and bumblebee populations.
RESUMO
World-wide declines in pollinators, including bumblebees, are attributed to a multitude of stressors such as habitat loss, resource availability, emerging viruses and parasites, exposure to pesticides, and climate change, operating at various spatial and temporal scales. Disentangling individual and interacting effects of these stressors, and understanding their impact at the individual, colony and population level are a challenge for systems ecology. Empirical testing of all combinations and contexts is not feasible. A mechanistic multilevel systems model (individual-colony-population-community) is required to explore resilience mechanisms of populations and communities under stress.We present a model which can simulate the growth, behaviour and survival of six UK bumblebee species living in any mapped landscape. Bumble-BEEHAVE simulates, in an agent-based approach, the colony development of bumblebees in a realistic landscape to study how multiple stressors affect bee numbers and population dynamics. We provide extensive documentation, including sensitivity analysis and validation, based on data from literature. The model is freely available, has flexible settings and includes a user manual to ensure it can be used by researchers, farmers, policy-makers, NGOs or other interested parties.Model outcomes compare well with empirical data for individual foraging behaviour, colony growth and reproduction, and estimated nest densities.Simulating the impact of reproductive depression caused by pesticide exposure shows that the complex feedback mechanisms captured in this model predict higher colony resilience to stress than suggested by a previous, simpler model. Synthesis and applications. The Bumble-BEEHAVE model represents a significant step towards predicting bumblebee population dynamics in a spatially explicit way. It enables researchers to understand the individual and interacting effects of the multiple stressors affecting bumblebee survival and the feedback mechanisms that may buffer a colony against environmental stress, or indeed lead to spiralling colony collapse. The model can be used to aid the design of field experiments, for risk assessments, to inform conservation and farming decisions and for assigning bespoke management recommendations at a landscape scale.
RESUMO
BACKGROUND: Impaired cerebral autoregulation in preterm infants makes circulatory management important to avoid cerebral hypoxic-ischemic injury. Dobutamine is frequently used as inotropic treatment in preterm neonates, but its effects on the brain exposed to cerebral hypoxia are unknown. We hypothesized that dobutamine would protect the immature brain from cerebral hypoxic injury. METHODS: In preterm (0.6 gestation) fetal sheep, dobutamine (Dob, 10 µg/kg/min) or saline (Sal) was infused intravenously for 74 h. Two hours after the beginning of the infusion, umbilical cord occlusion (UCO) was performed to produce fetal asphyxia (Sal+UCO: n = 9, Dob+UCO: n = 7), or sham occlusion (Sal+sham: n = 7, Dob+sham: n = 6) was performed. Brains were collected 72 h later for neuropathology. RESULTS: Dobutamine did not induce cerebral changes in the sham UCO group. UCO increased apoptosis and microglia density in white matter, hippocampus, and caudate nucleus, and astrocyte density in the caudate nucleus. Dobutamine commenced before UCO reduced microglia infiltration in the white matter, and microglial and astrocyte density in the caudate. CONCLUSION: In preterm hypoxia-induced brain injury, dobutamine decreases neuroinflammation in the white matter and caudate, and reduces astrogliosis in the caudate. Early administration of dobutamine in preterm infants for cardiovascular stabilization appears safe and may be neuroprotective against unforeseeable cerebral hypoxic injury.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Dobutamina/uso terapêutico , Hipóxia Fetal/tratamento farmacológico , Hipóxia-Isquemia Encefálica/patologia , Inflamação/tratamento farmacológico , Animais , Asfixia Neonatal/patologia , Gasometria , Peso Corporal , Modelos Animais de Doenças , Dopamina/farmacologia , Eletrocardiografia , Feminino , Frequência Cardíaca , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Inflamação/patologia , Microglia , Neurônios , Tamanho do Órgão , Estresse Oxidativo , Gravidez , Prenhez , OvinosAssuntos
Benzoatos/imunologia , Dessensibilização Imunológica/métodos , Quelantes de Ferro/uso terapêutico , Triazóis/imunologia , Talassemia beta/tratamento farmacológico , Benzoatos/efeitos adversos , Benzoatos/uso terapêutico , Pré-Escolar , Deferasirox , Feminino , Humanos , Quelantes de Ferro/efeitos adversos , Triazóis/efeitos adversos , Triazóis/uso terapêutico , Talassemia beta/imunologiaRESUMO
Cambodia is prone to extreme weather events, especially floods, droughts and typhoons. Climate change is predicted to increase the frequency and intensity of such events. The Cambodian population is highly vulnerable to the impacts of these events due to poverty; malnutrition; agricultural dependence; settlements in flood-prone areas, and public health, governance and technological limitations. Yet little is known about the health impacts of extreme weather events in Cambodia. Given the extremely low adaptive capacity of the population, this is a crucial knowledge gap. A literature review of the health impacts of floods, droughts and typhoons in Cambodia was conducted, with regional and global information reviewed where Cambodia-specific literature was lacking. Water-borne diseases are of particular concern in Cambodia, in the face of extreme weather events and climate change, due to, inter alia, a high pre-existing burden of diseases such as diarrhoeal illness and a lack of improved sanitation infrastructure in rural areas. A time-series analysis under quasi-Poisson distribution was used to evaluate the association between floods and diarrhoeal disease incidence in Cambodian children between 2001 and 2012 in 16 Cambodian provinces. Floods were significantly associated with increased diarrhoeal disease in two provinces, while the analysis conducted suggested a possible protective effect from toilets and piped water. Addressing the specific, local pre-existing vulnerabilities is vital to promoting population health resilience and strengthening adaptive capacity to extreme weather events and climate change in Cambodia.