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BACKGROUND: The final year of life is often associated with increasing health complexities and use of health services. This frequently includes admission to an acute hospital which may or may not convey overall benefit. This uncertainty makes decisions regarding admission complex for clinicians. There is evidence of much variation in approaches to admission. AIMS: To explore how Primary Care clinicians approach hospitalisation decisions for people in the final year of life. DESIGN: Systematic literature review and narrative synthesis. DATA SOURCES: We searched the following databases from inception to April 2023: CINAHL, Cochrane Library, Embase, MedLine, PsychInfo and Web of Science followed by reference and forward citation reviews of included records. RESULTS: A total of 18 studies were included: 14 qualitative, 3 quantitative and 1 mixed methods study. As most of the results were qualitative, we performed a thematic analysis with narrative synthesis. Six key themes were identified: navigating the views of other stakeholders; clinician attributes; clinician interpretation of events; the perceived adequacy of the current setting and the alternatives; system factors and continuity of care. CONCLUSION: This review shows that a breadth of factors influence hospitalisation decisions. The views of other stakeholders take great importance but it is not clear how these views are, or should be, should be balanced. Clinician factors, such as experience with palliative care and clinical judgement, are also important. Future research should focus on how different aspects of the decision are balanced and to consider if, and how, this could be improved to optimise patient-centred outcomes and use of health resources.
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Counseling techniques are an important component of genetic counseling training and are focused on the person-centered counseling philosophy. While this has a long tradition within the profession and underpins the empowerment goal, it should not limit consideration of the potential benefits of education on other psychotherapeutic approaches such as the cognitive philosophy. The goal of empowerment in genetic counseling requires patients to receive information in a way that is accessible to them and to make sense of it in relation to their own health, lifestyle, and family information. This assimilation of new information is a complex cognitive process, and yet it is one that genetic counselors do not routinely actively facilitate. Rather the counseling component of genetic counseling has traditionally focused on emotionally supporting the patient which is driven by the person-centered philosophy that is covered in genetic counseling training. This paper argues for the potential for adopting more cognitive approaches informed by cognitive-behavioral therapy (CBT) and acceptance and commitment therapy (ACT), as these short interventions can have wide impact, including engaging patients who do not want to discuss feelings, helping people to make sense of information (not just gain knowledge), and helping people to change the relationship they have with their thoughts. This paper advocates for an introduction to CBT and ACT to be incorporated into prequalification training and for more advanced training to be available to postqualification genetic counselors.
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Terapia de Aceitação e Compromisso , Terapia Cognitivo-Comportamental , Humanos , Aconselhamento Genético , Terapia Cognitivo-Comportamental/métodos , Aconselhamento , EmoçõesRESUMO
Counseling techniques are an important part of genetic counseling, and teaching of the humanistic person-centered philosophy has been central to genetic counselor (GC) training. However, other psychotherapeutic approaches, especially cognitive approaches, may also be beneficial for the GC to have in their toolkit. This paper reports on a co-production workshop with newly qualified GCs where the potential for adopting more cognitive approaches informed by cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) was explored. Attendees were taught about the approaches and the rationale for their use in genetic counseling and had a chance to discuss their reactions and ideas for application. The attendees saw great potential for the approaches within their practice, feeling that these short interventions can have a wide impact, including engaging patients who do not want to discuss feelings, helping people to make sense of information (not just gain knowledge), and helping people to change the relationship they have with their thoughts. They were able to identify when they already use some cognitive approaches in their practice, and to see how they could build on this to provide better patient care. The paper advocates for an introduction to CBT and ACT to be incorporated into pre-qualification training, and for more advanced training to be available to post-qualification GCs.
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Terapia de Aceitação e Compromisso , Terapia Cognitivo-Comportamental , Conselheiros , Humanos , Aconselhamento Genético , AconselhamentoRESUMO
PI3-kinase (PI3K) is an intracellular signaling complex that is stimulated upon cocaine exposure and linked with the behavioral consequences of cocaine. We recently genetically silenced the PI3K p110ß subunit in the medial prefrontal cortex following repeated cocaine in mice, reinstating the capacity of these mice to engage in prospective goal-seeking behavior. In the present short report, we address two follow-up hypotheses: 1) The control of decision-making behavior by PI3K p110ß is attributable to neuronal signaling, and 2) PI3K p110ß in the healthy (i.e., drug-naïve) medial prefrontal cortex has functional consequences in the control of reward-related decision-making strategies. In Experiment 1, we found that silencing neuronal p110ß improved action flexibility following cocaine. In Experiment 2, we reduced PI3K p110ß in drug-naïve mice that were extensively trained to respond for food reinforcers. Gene silencing caused mice to abandon goal-seeking strategies, unmasking habit-based behaviors that were propelled by interactions with the nucleus accumbens. Thus, PI3K control of goal-directed action strategies appears to act in accordance with an inverted U-shaped function, with "too much" (following cocaine) or "too little" (following p110ß subunit silencing) obstructing goal seeking and causing mice to defer to habit-like response sequences.
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Cocaína , Fosfatidilinositol 3-Quinases , Camundongos , Animais , Estudos Prospectivos , Cocaína/farmacologia , Recompensa , Córtex Pré-Frontal/fisiologiaRESUMO
During the COVID-19 pandemic, most data on adherence to health protective behaviours were collected via a self-report. We quantified the discrepancy between self-report data and discretely observed behaviour in a sample of university staff and students. We assessed the prevalence of cleaning hands, wearing a face-covering and maintaining distance from others. We also tested whether additional signage reminding people that these behaviours were mandatory improved observed adherence. Prevalence estimates based on self-report were higher than those based on observations. Signage was associated with improvements for observed behaviours (all χ2 ≥ 6.0, P < 0.05). We caution that self-reported data can produce misleading adherence rates.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Universidades , Autorrelato , Pandemias/prevenção & controle , Comportamentos Relacionados com a SaúdeRESUMO
Repeated cocaine exposure causes dendritic spine loss in the orbitofrontal cortex, which might contribute to poor orbitofrontal cortical function following drug exposure. One challenge, however, has been verifying links between neuronal structural plasticity and behavior, if any. Here we report that cocaine self-administration triggers the loss of dendritic spines on excitatory neurons in the orbitofrontal cortex of male and female mice (as has been reported in rats). To understand functional consequences, we locally ablated neuronal ß1-integrins, cell adhesion receptors that adhere cells to the extracellular matrix and thus support dendritic spine stability. Degradation of ß1-integrin tone: 1) caused dendritic spine loss; 2) exaggerated cocaine-seeking responses in a cue-induced reinstatement test; and 3) impaired the ability of mice to integrate new learning into familiar routines - a key function of the orbitofrontal cortex. Stimulating Abl-related gene (Arg) kinase, over-expressing Proline-rich tyrosine kinase (Pyk2), and inhibiting Rho-associated coiled-coil containing kinase (ROCK) corrected response strategies, uncovering a ß1-integrin-mediated signaling axis that controls orbitofrontal cortical function. Finally, use of a combinatorial gene silencing/chemogenetic strategy revealed that ß1-integrins support the ability of mice to integrate new information into established behaviors by sustaining orbitofrontal cortical connections with the basolateral amygdala.SIGNIFICANCE STATEMENTCocaine degenerates dendritic spines in the orbitofrontal cortex, a region of the brain involved in interlacing new information into established behaviors. One challenge has been verifying links between cellular structural stability and behavior, if any. In this second of two related investigations, we study integrin family receptors, which adhere cells to the extracellular matrix and thereby stabilize dendritic spines (see also DePoy et al., 2019, Journal of Neuroscience). We reveal that ß1-integrins in the orbitofrontal cortex control food- and cocaine-seeking behaviors. For instance, ß1-integrin loss amplifies cocaine-seeking behavior and impairs the ability of mice to integrate new learning into familiar routines. We identify likely intracellular signaling partners by which ß1-integrins support orbitofrontal cortical function and connectivity with the basolateral amygdala.
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Bone morphogenetic protein 9 (BMP9) and BMP10 are circulating ligands that mediate endothelial cell (EC) protection via complexes of the type I receptor ALK1 and the type II receptors activin type-IIA receptor (ACTR-IIA) and bone morphogenetic type II receptor (BMPR-II). We previously demonstrated that BMP9 induces the expression of interleukin-6, interleukin-8 and E-selectin in ECs and might influence their interactions with monocytes and neutrophils. We asked whether BMP9 and BMP10 regulate the expression of chemokine (C-C motif) ligand 2 (CCL2), a key chemokine involved in monocyte-macrophage chemoattraction. Here, we show that BMP9 and BMP10 repress basal CCL2 expression and release from human pulmonary artery ECs and aortic ECs. The repression was dependent on ALK1 and co-dependent on ACTR-IIA and BMPR-II. Assessment of canonical Smad signalling indicated a reliance of this response on Smad4. Of note, Smad1/5 signalling contributed only at BMP9 concentrations similar to those in the circulation. In the context of inflammation, BMP9 did not alter the induction of CCL2 by TNF-α. As CCL2 promotes monocyte/macrophage chemotaxis and endothelial permeability, these data support the concept that BMP9 preserves basal endothelial integrity.
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Células Endoteliais , Fator 2 de Diferenciação de Crescimento , Receptores de Activinas Tipo II , Proteínas Morfogenéticas Ósseas , Quimiocina CCL2/genética , Fator 2 de Diferenciação de Crescimento/genética , Humanos , Fatores de ProteçãoRESUMO
OBJECTIVES: To assess the quantity and quality of studies using an observational measure of behaviour during the COVID-19 pandemic, and to narratively describe the association between self-report and observational data for behaviours relevant to controlling an infectious disease outbreak. DESIGN: Systematic review and narrative synthesis of observational studies. DATA SOURCES: We searched Medline, Embase, PsychInfo, Publons, Scopus and the UK Health Security Agency behavioural science LitRep database from inception to 17th September 2021 for relevant studies. STUDY SELECTION: We included studies which collected observational data of at least one of three health protective behaviours (hand hygiene, face covering use and maintaining physical distance from others ('social distancing') during the COVID-19 pandemic. Studies where observational data were compared to self-report data in relation to any infectious disease were also included. DATA EXTRACTION AND SYNTHESIS: We evaluated the quality of studies using the NIH quality assessment scale for observational studies, extracted data on sample size, setting and adherence to health protective behaviours, and synthesized results narratively. RESULTS: Of 27,279 published papers on COVID-19 relevant health protective behaviours that included one or more terms relating to hand hygiene, face covering and social distancing, we identified 48 studies that included an objective observational measure. Of these, 35 assessed face covering use, 17 assessed hand hygiene behaviour and seven assessed physical distancing. The general quality of these studies was good. When expanding the search to all infectious diseases, we included 21 studies that compared observational versus self-report data. These almost exclusively studied hand hygiene. The difference in outcomes was striking, with self-report over-estimating observed adherence by up to a factor of five in some settings. In only four papers did self-report match observational data in any domains. CONCLUSIONS: Despite their importance in controlling the pandemic, we found remarkably few studies assessing protective behaviours by observation, rather than self-report, though these studies tended to be of reasonably good quality. Observed adherence tends to be substantially lower than estimates obtained via self-report. Accurate assessment of levels of personal protective behaviour, and evaluation of interventions to increase this, would benefit from the use of observational methods.
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COVID-19 , COVID-19/prevenção & controle , Humanos , Controle de Infecções , Pandemias/prevenção & controle , Distanciamento Físico , AutorrelatoRESUMO
Health-related quality of life (HRQoL) scores assess symptom burden in pulmonary arterial hypertension (PAH) but data regarding their role in prognostication and risk stratification are limited. We assessed these relationships using the emPHasis-10 HRQoL measure.1745 patients with idiopathic PAH (IPAH), drug-induced PAH (DPAH), heritable PAH (HPAH) (collectively "(I/D/H)PAH"), or connective tissue disease-associated PAH (CTD-PAH), who had completed emPHasis-10 questionnaires at one of six UK referral centres between 2014 and 2017, were identified. Correlations with exercise capacity and World Health Organization (WHO) functional class were assessed, and exploratory risk stratification thresholds were tested.Moderate correlations were seen between emPHasis-10 scores and 6-min walk distance (r=-0.546), incremental shuttle walk distance (r=-0.504) and WHO functional class (r=0.497) (all p<0.0001). Distribution of emPHasis-10 score differed significantly between each WHO functional class (all p<0.0001). On multivariate analysis, emPHasis-10 score, but not WHO functional class, was an independent predictor of mortality. In a risk stratification approach, scores of 0-16, 17-33 and 34-50 identified incident patients with 1-year mortality of 5%, 10% and 23%, respectively. Survival of patients in WHO functional class III could be further stratified using an emPHasis-10 score ≥34 (p<0.01). At follow-up, patients with improved emPHasis-10 scores had improved exercise capacity (p<0.0001) and patients who transitioned between risk groups demonstrated similar survival to patients originally in those risk groups.The emPHasis-10 score is an independent prognostic marker in patients with (I/D/H)PAH or CTD-PAH. It has utility in risk stratification in addition to currently used parameters. Improvement in emPHasis-10 score is associated with improved exercise capacity.
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Doenças do Tecido Conjuntivo , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Doenças do Tecido Conjuntivo/complicações , Humanos , Qualidade de Vida , Reino UnidoRESUMO
BACKGROUND: The risk of complications, including death, is substantially increased in patients with pulmonary hypertension (PH) undergoing anaesthesia for surgical procedures, especially in those with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH). Sedation also poses a risk to patients with PH. Physiological changes including tachycardia, hypotension, fluid shifts, and an increase in pulmonary vascular resistance (PH crisis) can precipitate acute right ventricular decompensation and death. METHODS: A systematic literature review was performed of studies in patients with PH undergoing non-cardiac and non-obstetric surgery. The management of patients with PH requiring sedation for endoscopy was also reviewed. Using a framework of relevant clinical questions, we review the available evidence guiding operative risk, risk assessment, preoperative optimisation, and perioperative management, and identifying areas for future research. RESULTS: Reported 30 day mortality after non-cardiac and non-obstetric surgery ranges between 2% and 18% in patients with PH undergoing elective procedures, and increases to 15-50% for emergency surgery, with complications and death usually relating to acute right ventricular failure. Risk factors for mortality include procedure-specific and patient-related factors, especially markers of PH severity (e.g. pulmonary haemodynamics, poor exercise performance, and right ventricular dysfunction). Most studies highlight the importance of individualised preoperative risk assessment and optimisation and advanced perioperative planning. CONCLUSIONS: With an increasing number of patients requiring surgery in specialist and non-specialist PH centres, a systematic, evidence-based, multidisciplinary approach is required to minimise complications. Adequate risk stratification and a tailored-individualised perioperative plan is paramount.
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Consenso , Prova Pericial/normas , Hipertensão Pulmonar/cirurgia , Assistência Perioperatória/normas , Complicações Pós-Operatórias/prevenção & controle , Prova Pericial/métodos , Humanos , Hipertensão Pulmonar/diagnóstico , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/diagnósticoRESUMO
In England, publicly funded couples therapy is reserved for couples where one or both partners present with psychological disorders, rather than relationship distress, despite evidence of a bidirectional relationship between the two. Demographics and presenting issues for 14,726 couples who received counseling through a third-sector counseling organization in England and Wales were investigated. Clients were often White, aged 25-54, and presented with interpersonal issues. "Mental health problems" were identified as an issue by about a quarter of all clients. This suggests that many couples seeking relationship counseling wish to address relational versus psychological distress, which has implications for publicly funded services.
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Aconselhamento/estatística & dados numéricos , Terapia de Casal/estatística & dados numéricos , Conflito Familiar , Relações Interpessoais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido/epidemiologia , Adulto JovemRESUMO
Given over 2.77 million US service members have been deployed in the past 20 years and the intense process of reintegration to civilian life, understanding factors that contribute to Veterans' mental health and substance use is critical. This study sought to understand the effects of US identity exploration, US identity commitment, US identity affirmation, and US identity centrality on substance use and symptoms of depression and anxiety. The sample consisted of 195 US military Veterans (n = 184, 53.3% women; 73.3% White; Mage = 35.12 years, SD = 9.60 years). Bivariate correlations indicated US identity affirmation was negatively associated with substance use and symptoms of depression and anxiety whereas US identity centrality was positively correlated with alcohol use. Utilizing structural equation model, US identity affirmation and US identity centrality were, respectively, negatively and positively associated with alcohol use, substance use, and symptoms of depression and anxiety. Partially consistent with our hypothesis, US identity exploration was positively associated with symptoms of anxiety. In contrast to our hypothesis, US identity commitment was not significantly associated with any outcome. Results are discussed in terms of important directions for identity research in the transition to civilian life.
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INTRODUCTION: The objective of this study was to examine the outcomes and interventions in pregnant women presenting with a perception of reduced fetal movements (RFM), and to determine if repeated episodes of RFM increase the risk of adverse outcomes. MATERIAL AND METHODS: This was a retrospective cohort study conducted in six NHS hospitals within the Thames Valley network region, UK and one neighboring hospital, an area with approximately 31 000 births annually. All women with a primary presentation of perceived RFM after 24 completed weeks of gestation during the month of October 2016 were included in the study. Prospective records in all units were examined and individual case-notes were reviewed. Pregnancy and neonatal outcomes and their relation with recurrent presentations with RFM were examined using relative risks with 95% CI. The main outcome measures are described. Neonatal outcomes measured were perinatal mortality, neonatal unit admission, abnormal cardiotocography at presentation, a composite severe morbidity outcome of Apgar <7 at 5 minutes or arterial pH <7.0 or encephalopathy, and birthweight. Pregnancy outcomes measured were induction of labor, cesarean section, admission and ultrasound usage rates. RESULTS: In all, 591 women presented with RFM during the month; using annual hospital birth figures, the incidence of RFM was estimated at 22.6% (range 14.9%-32.5%). More than 1 presentation of RFM occurred in 273 (46.2%). All 3 deaths (0.5%) were at the first presentation. More than 1 presentation was associated with higher induction rates (56.0% vs 31.9%), but no increase in any adverse outcomes including small-for-gestational-age. CONCLUSIONS: Reduced fetal movements, and recurrent episodes, are common, and lead to considerable resource usage and obstetric intervention. We found no evidence to suggest that recurrent episodes increase pregnancy risk.
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Retardo do Crescimento Fetal/diagnóstico por imagem , Movimento Fetal/fisiologia , Recém-Nascido Pequeno para a Idade Gestacional , Resultado da Gravidez , Natimorto , Ultrassonografia Pré-Natal , Adulto , Cardiotocografia/métodos , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Retrospectivos , Medição de Risco , Reino UnidoRESUMO
Mindfulness-based approaches have been suggested as possible methods to treat moral injury in military personnel. However, empirical research has yet to evaluate if mindfulness acts as a protective factor for the possible negative effects of moral injury, such as alcohol use, drug use, or posttraumatic stress disorder (PTSD) symptoms. In this study, we investigated if five facets of mindfulness (i.e., observing, nonjudging, nonreactivity, awareness, and describing) moderated associations between moral injury and the outcomes of PTSD symptoms, alcohol misuse, and drug abuse symptoms in a sample of military personnel. Participants were 244 military personnel (the majority were former military members) who had been deployed at least once during the Iraq War, War in Afghanistan, other wars, or humanitarian missions. The study results indicated that nonjudging, ß = -.22, and awareness, ß = -.25, had significant attenuating effects on the association between moral injury and drug abuse symptoms. However, observing, ß = .17; nonreactivity, ß = .23; and describing, ß = .15, had significant synergistic effects (i.e., they strengthened the association between moral injury and drug abuse symptoms). There were no significant moderation effects on the associations between moral injury and PTSD symptoms or between moral injury and alcohol misuse. Our results provide initial evidence that not all facets of mindfulness may protect against the challenges of coping with moral injury. Directions for future research and implications for practice are discussed.
Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Daño moral, uso de sustancias y síntomas de TEPT entre el personal militar: un examen de la atención consciente de los rasgos como moderador MINDFULNESS Y DAÑO MORAL EN VETERANOS Se han sugerido enfoques basados ââen la atención plena (o mindfulness en inglés) como posibles métodos para tratar el daño moral en el personal militar. Sin embargo, la investigación empírica aún debe evaluar si la atención plena actúa como un factor protector para los posibles efectos negativos del daño moral, como el consumo de alcohol, el uso de drogas o los síntomas del trastorno de estrés postraumático (TEPT). En este estudio, investigamos si cinco facetas de la atención plena (es decir, observar, no juzgar, no reaccionar, conciencia y describir) moderaron las asociaciones entre daño moral y los resultados de los síntomas del TEPT, el uso indebido del alcohol y los síntomas del abuso de drogas en una muestra de personal militar. Los participantes eran 244 militares (la mayoría de ellos ex militares) que habían sido desplegados al menos una vez durante la Guerra de Irak, la Guerra en Afganistán, otras guerras o misiones humanitarias. Los resultados del estudio indicaron que el no juzgar, ß = −.22, y la conciencia ß = −.25, tuvieron efectos atenuantes significativos en la asociación entre daño moral y síntomas de abuso de drogas. Sin embargo, observar, ß = .17; no reactividad, ß = .23; y describir, ß = .15, tuvo efectos sinérgicos significativos (es decir, fortalecieron la asociación entre daño moral y los síntomas de abuso de drogas). No hubo efectos significativos de moderación en las asociaciones entre el daño moral y los síntomas del TEPT o entre el daño moral y el abuso del alcohol. Nuestros resultados proporcionan evidencia inicial de que no todas las facetas de la atención plena pueden proteger contra los desafíos de enfrentar el daño moral. Se discuten lineamientos para futuras investigaciones y las implicaciones para la práctica.
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Militares/psicologia , Atenção Plena/métodos , Princípios Morais , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Autorrelato , Espiritualidade , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/etiologiaRESUMO
Rad50-interacting protein 1 (Rint1) associates with the DNA damage response protein Rad50 during the transition from the S phase to the G2/M phase and functions in radiation-induced G2 checkpoint control. It has also been demonstrated that Rint1 is essential in vesicle trafficking from the Golgi apparatus to the endoplasmic reticulum (ER) through an interaction with Zeste-White 10 (ZW10). We have isolated a novel interaction between Rint1 and the human papillomavirus 16 (HPV16) transcription and replication factor E2. E2 binds to Rint1 within its ZW10 interaction domain, and we show that in the absence of E2, Rint1 is localized to the ER and associates with ZW10. E2 expression results in a disruption of the Rint1-ZW10 interaction and an accumulation of nuclear Rint1, coincident with a significant reduction in vesicle movement from the ER to the Golgi apparatus. Interestingly, nuclear Rint1 and members of the Mre11/Rad50/Nbs1 (MRN) complex were found in distinct E2 nuclear foci, which peaked during mid-S phase, indicating that the recruitment of Rint1 to E2 foci within the nucleus may also result in the recruitment of this DNA damage-sensing protein complex. We show that exogenous Rint1 expression enhances E2-dependent virus replication. Conversely, the overexpression of a truncated Rint1 protein that retains the E2 binding domain but not the Rad50 binding domain acts as a dominant negative inhibitor of E2-dependent HPV replication. Put together, these experiments demonstrate that the interaction between Rint1 and E2 has an important function in HPV replication.IMPORTANCE HPV infections are an important driver of many epithelial cancers, including those within the anogenital and oropharyngeal tracts. The HPV life cycle is tightly regulated and intimately linked to the differentiation of the epithelial cells that it infects. HPV replication factories formed in the nucleus are locations where viral DNA is copied to support virus persistence and amplification of infection. The recruitment of specific cellular protein complexes to these factories aids efficient and controlled viral replication. We have identified a novel HPV-host interaction that functions in the cellular response to DNA damage and cell cycle control. We show that the HPV E2 protein targets Rad50-interacting protein 1 (Rint1) to facilitate virus genome replication. These findings add to our understanding of how HPV replicates and the host cell pathways that are targeted by HPV to support virus replication. Understanding these pathways will allow further research into novel inhibitors of HPV genome replication.
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Proteínas de Ciclo Celular/metabolismo , Replicação do DNA , Proteínas de Ligação a DNA/metabolismo , Papillomavirus Humano 16/fisiologia , Proteínas Oncogênicas Virais/metabolismo , Replicação Viral , Sequência de Aminoácidos , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , DNA Viral/biossíntese , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Domínios e Motivos de Interação entre Proteínas , Transporte Proteico , Origem de Replicação , Pontos de Checagem da Fase S do Ciclo CelularRESUMO
Treatment of acute emergencies in patients with pulmonary arterial hypertension (PAH) can be challenging. In the UK and Ireland, management of adult patients with PAH is centred in eight nationally designated pulmonary hypertension (PH) centres. However, many patients live far from these centres and physicians in local hospitals are often required to manage PAH emergencies. A committee of physicians from nationally designated PH centres identified the 'most common' emergency clinical scenarios encountered in patients with PAH. Thereafter, a review of the literature was performed centred on these specified topics and a management approach was developed based on best available evidence and expert consensus. Management protocols were developed on the following PAH emergencies: chest pain (including myocardial ischaemia), right ventricular failure, arrhythmias, sepsis, haemoptysis ('CRASH'), as well as considerations relevant to surgery, anaesthesia and pregnancy. Emergencies are not uncommon in PAH. While expertise in PAH management is essential, all physicians involved in acute care should be aware of the principles of acute management of PAH emergencies. A multidisciplinary approach is necessary, with physicians from tertiary PH centres supporting care locally and planning safe transfer of patients to PH centres when appropriate.
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Cuidados Críticos , Hipertensão Pulmonar/terapia , Papel do Médico , Arritmias Cardíacas/etiologia , Bacteriemia/microbiologia , Dor no Peito/etiologia , Ensaios Clínicos como Assunto , Medicina Baseada em Evidências , Hemoptise/etiologia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/mortalidade , Irlanda , Guias de Prática Clínica como Assunto , Prognóstico , Fatores de Risco , Resultado do Tratamento , Reino Unido , Disfunção Ventricular Direita/etiologiaRESUMO
OBJECTIVE: To evaluate impact of WHO checklist compliance on risk-adjusted clinical outcomes, including the influence of checklist components (Sign-in, Time-out, Sign-out) on outcomes. BACKGROUND: There remain unanswered questions surrounding surgical checklists as a quality and safety tool, such as the impact in cases of differing complexity and the extent of checklist implementation. METHODS: Data were collected from surgical admissions (6714 patients) from March 2010 to June 2011 at 5 academic and community hospitals. The primary endpoint was any complication, including mortality, occurring before hospital discharge. Checklist usage was recorded as checklist completed in full/partly. Multilevel modeling was performed to investigate the association between complications/mortality and checklist completion. RESULTS: Significant variability in checklist usage was found: although at least 1 of the 3 components was completed in 96.7% of cases, the entire checklist was only completed in 62.1% of cases. Checklist completion did not affect mortality reduction, but significantly lowered risk of postoperative complication (16.9% vs. 11.2%), and was largely noticed when all 3 components of the checklist had been completed (odds ratio = 0.57, 95% confidence interval: 0.37-0.87, P < 0.01). Calculated population-attributable fractions showed that 14% (95% confidence interval: 7%-21%) of the complications could be prevented if full completion of the checklist was implemented. CONCLUSIONS: Checklist implementation was associated with reduced case-mix-adjusted complications after surgery and was most significant when all 3 components of the checklist were completed. Full, as opposed to partial, checklist completion provides a health policy opportunity to improve checklist impact on surgical safety and quality of care.
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Lista de Checagem , Fidelidade a Diretrizes , Avaliação de Resultados da Assistência ao Paciente , Risco Ajustado , Procedimentos Cirúrgicos Operatórios/normas , Humanos , Estudos Longitudinais , Complicações Pós-Operatórias/prevenção & controle , Organização Mundial da SaúdeRESUMO
OBJECTIVES: To evaluate how the World Health Organization (WHO) surgical safety checklist was implemented across hospitals in England; to identify barriers and facilitators toward implementation; and to draw out lessons for implementing improvement initiatives in surgery/health care more generally. BACKGROUND: The WHO checklist has been linked to improved surgical outcomes and teamwork, yet we know little about the factors affecting its successful uptake. METHODS: A longitudinal interview study with operating room personnel was conducted across a representative sample of 10 hospitals in England between March 2010 and March 2011. Interviews were audio recorded over the phone. Interviewees were asked about their experience of how the checklist was introduced and the factors that hindered or aided this process. Transcripts were submitted to thematic analysis. RESULTS: A total of 119 interviews were completed. Checklist implementation varied greatly between and within hospitals, ranging from preplanned/phased approaches to the checklist simply "appearing" in operating rooms, or staff feeling it had been imposed. Most barriers to implementation were specific to the checklist itself (eg, perceived design issues) but also included problematic integration into preexisting processes. The most common barrier was resistance from senior clinicians. The facilitators revealed some positive steps that can been taken to prevent/address these barriers, for example, modifying the checklist, providing education/training, feeding-back local data, fostering strong leadership (particularly at attending level), and instilling accountability. CONCLUSIONS: We identified common themes that have aided or hindered the introduction of the WHO checklist in England and have translated these into recommendations to guide the implementation of improvement initiatives in surgery and wider health care systems.
Assuntos
Lista de Checagem , Hospitais/normas , Segurança do Paciente , Gestão da Segurança , Procedimentos Cirúrgicos Operatórios/normas , Organização Mundial da Saúde , Atitude do Pessoal de Saúde , Inglaterra , Estudos de Avaliação como Assunto , Fidelidade a Diretrizes , Política de Saúde , Humanos , Entrevistas como Assunto , Liderança , Estudos LongitudinaisRESUMO
Many established models of animal foraging assume that individuals are ecologically equivalent. However, it is increasingly recognized that populations may comprise individuals who differ consistently in their diets and foraging behaviors. For example, recent studies have shown that individual foraging site fidelity (IFSF, when individuals consistently forage in only a small part of their population's home range) occurs in some colonial breeders. Short-term IFSF could result from animals using a win-stay, lose-shift foraging strategy. Alternatively, it may be a consequence of individual specialization. Pelagic seabirds are colonial central-place foragers, classically assumed to use flexible foraging strategies to target widely dispersed, spatiotemporally patchy prey. However, tracking has shown that IFSF occurs in many seabirds, although it is not known whether this persists across years. To test for long-term IFSF and to examine alternative hypotheses concerning its cause, we repeatedly tracked 55 Northern Gannets (Morus bassanus) from a large colony in the North Sea within and across three successive breeding seasons. Gannets foraged in neritic waters, predictably structured by tidal mixing and thermal stratification, but subject to stochastic, wind-induced overturning. Both within and across years, coarse to mesoscale (tens of kilometers) IFSF was significant but not absolute, and foraging birds departed the colony in individually consistent directions. Carbon stable isotope ratios in gannet blood tissues were repeatable within years and nitrogen ratios were also repeatable across years, suggesting long-term individual dietary specialization. Individuals were also consistent across years in habitat use with respect to relative sea surface temperature and in some dive metrics, yet none of these factors accounted for IFSF. Moreover, at the scale of weeks, IFSF did not decay over time and the magnitude of IFSF across years was similar to that within years, suggesting that IFSF is not primarily the result of win-stay, lose-shift foraging. Rather, we hypothesize that site familiarity, accrued early in-life, causes IFSF by canalizing subsequent foraging decisions. Evidence from this and other studies suggests that IFSF may be common in colonial central-place foragers, with far-reaching consequences for our attempts to understand and conserve these animals in a rapidly changing environment.
Assuntos
Aves/fisiologia , Comportamento Alimentar/fisiologia , Distribuição Animal , Animais , Composição Corporal , Ecossistema , Isótopos , Fatores de TempoRESUMO
BACKGROUND: Despite the increased prevalence of bioethics research that seeks to use empirical data to answer normative research questions, there is no consensus as to what an appropriate methodology for this would be. This review aims to search the literature, present and critically discuss published Empirical Bioethics methodologies. METHODS: MedLine, Web of Science and Google Scholar were searched between 15/02/12 and 16/06/13 to find relevant papers. These were abstract reviewed independently by two reviewers with papers meeting the inclusion criteria subjected to data extraction. RESULTS: 33 publications (32 papers and one book chapter) were included which contained 32 distinct methodologies. The majority of these methodologies (n = 22) can be classed as either dialogical or consultative, and these represent two extreme 'poles' of methodological orientation. Consideration of these results provoked three central questions that are central to the planning of an empirical bioethics study, and revolve around how a normative conclusion can be justified, the analytic process through which that conclusion is reached, and the kind of conclusion that is sought. CONCLUSION: When considering which methodology or research methods to adopt in any particular study, researchers need to think carefully about the nature of the claims they wish to generate through their analyses, and how these claims align with the aims of the research. Whilst there are superficial similarities in the ways that identical research methods are made use of, the different meta-ethical and epistemological commitments that undergird the range of methodological approaches adopted rehearse many of the central foundational disagreements that play out within moral philosophy and bioethical analysis more broadly. There is little common ground that transcends these disagreements, and we argue that this is likely to present a challenge for the legitimacy of the bioethical enterprise. We conclude, however, that this heterogeneity ought to be welcomed, but urge those involved in the field to engage meaningfully and explicitly with questions concerning what kinds of moral claim they want to be able to make, about normative justification and the methodological process, and about the coherence of these components within their work.