Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 341
Filtrar
2.
J Prev Alzheimers Dis ; 9(2): 277-285, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35543001

RESUMO

BACKGROUND: Widespread lifestyle risk reduction at the community level is considered effective in decreasing Alzheimer's disease (AD). To address the limited use of risk deduction in AD, this study aimed to explore the feasibility of community-level implementation. Diverse older adults (60+) living in Richmond, VA, with incomes below $12,000/year and managing diabetic/cardiovascular symptoms were offered weekly lifestyle telephone-health coaching for 12-weeks in 2019-2020 (Phase 1). The health coaching sessions were framed to provide AD lifestyle risk reduction education, goal setting, and support: motivations and self-efficacy. The study sample (n=40, mean age 68 years (range: 60-76 years)) was 90% African American/Black (n=36), 100% Non-Hispanic, and 45% males (n=18). Twenty-five participants (60%) reported experiencing some/often memory problems in the last 12-months. Thirty-nine (95%) of subjects successfully participated in coaching sessions; on average, 11 (91.9%) sessions per subject were completed. Participants provided positive anecdotal feedback and stated the need for continued health coaching. Consequently, n=30 (75%) of the original sample consented to continued health coaching during the 2020-2021 COVID-19 pandemic (Phase 2). All study subjects were examined at baseline (Time 1), 3-month (Time 2), covid-baseline (Time 3), and 3-months postcovid-baseline (Time 4). Repeated Measures ANOVAs were done to examine Time and Time*Memory Status effects. RESULTS: There was a total risk reduction at Phase 1 (F=9.26; p=.004; effect size=.19). At Phase 2, alcohol use decreased (p=.05), quadratic time effects were observed in physical activity (p=.01-.02), and cubic time effects were observed in depression (p=.02). Overall, total risk reduction in Phase 2 was observed at F=5.05; p=.03 effect size=.16. Pre/post-test analyses indicated improvement in Memory Problem Time Interaction (p=.007), AD knowledge (p=.01-.03), and Tired Days (p=.04) across Phase 1. There was also improvement in Social Isolation Time Interaction (p=.03); Tobacco Addiction (p=.001); Poor Mental Health Days (p=.05), and Worried Days Time Interaction (p=.02-.01) across Phase 2. Between subject Memory Status effects, indicating poorer baseline levels for individuals reporting memory problems had greater improvement seen in memory complaints (p=.001), poor mental health days (.02), and tired days (.003-.01). CONCLUSIONS: This preliminary work creates the impetus for future large-scale lifestyle AD risk reduction investigations to mitigate and improve modifiable AD risk among low-income, diverse older adults, including individuals reporting memory problems. Our findings surrounding participant engagement and positive trends in AD risk reduction support the hypothesis that telephone-based health coaching is a practical and feasible AD risk reduction intervention.


Assuntos
Doença de Alzheimer , COVID-19 , Tutoria , Idoso , Doença de Alzheimer/prevenção & controle , Feminino , Humanos , Masculino , Pandemias , Telefone
4.
Integr Org Biol ; 3(1): obab020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34409260

RESUMO

Captive breeding can affect how sexual selection acts on subsequent generations. One context where this is important is in fish hatcheries. In many salmon hatcheries, spawning is controlled artificially and offspring are reared in captivity before release into the wild. While previous studies have suggested that hatchery- and natural-origin fish may make different mate choice decisions, it remains to be determined how hatchery fish may be making different mate choice decisions compared with natural-origin fish at a genetic level. Using genotyping-by-sequencing, we identify single-nucleotide polymorphisms (SNPs) associated with variation in mate pairings from a natural context involving hatchery- and natural-origin coho salmon (Oncorhynchus kisutch). In both natural-origin and hatchery mate pairs, we observed more SNPs with negative assortment than positive assortment. However, only 3% of the negative assortment SNPs were shared between the two mating groups, and 1% of the positive assortment SNPs were shared between the two mating groups, indicating divergence in mating cues between wild and hatchery-raised salmon. These findings shed light on mate choice in general and may have important implications in the conservation management of species as well as for improving other captive breeding scenarios. There remains much to discover about mate choice in salmon and research described here reflects our intent to test the potential of ongoing advances in population genomics to develop new hatchery practices that may improve the performance of hatchery offspring, lessening the differences and thus potential impacts upon wild stocks.

5.
BJA Educ ; 21(7): 270-277, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34178384
6.
Acad Med ; 96(8): 1205-1212, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33496432

RESUMO

PURPOSE: The financial impact of graduate medical education (GME) on teaching hospitals remains poorly understood, while calls for increased federal support continue alongside legislative threats to reduce funding. Despite studies suggesting that residents are more "economical" than alternative providers, GME is widely believed to be an expensive investment. Assumptions that residents increase the cost of patient care have persisted in the absence of convincing evidence to the contrary. Thus, the authors sought to examine resident influence on patient care costs by comparing costs between a resident-driven service (RS) and a nonresident-covered service (NRS), with attention to clinical outcomes and how potential cost differences relate to the utilization of resources, length of stay (LOS), and other factors. METHOD: This prospective study compared costs and clinical outcomes of internal medicine patients admitted to an RS versus an NRS at Massachusetts General Hospital (July 1, 2016-June 30, 2017). Total variable direct costs of inpatient admission was the primary outcome measure. LOS; 30-day readmission rate; utilization related to diagnostic radiology, pharmaceuticals, and clinical labs; and other outcome measures were also compared. Linear regression models quantified the relationship between log-transformed variable direct costs and service. RESULTS: Baseline characteristics of 5,448 patients on the 2 services (3,250 on an RS and 2,198 on an NRS) were similar. On an RS, patient care costs were slightly less and LOS was slightly shorter than on an NRS, with no significant differences in hospital mortality or 30-day readmission rate detected. Resource utilization was comparable between the services. CONCLUSIONS: These findings undermine long-held assumptions that residents increase the cost of patient care. Though not generalizable to ambulatory settings or other specialties, this study can help inform hospital decision making around sponsorship of GME programs, especially if federal funding for GME remains capped or is subject to additional reductions.


Assuntos
Pacientes Internados , Medicina Interna , Hospitais de Ensino , Humanos , Medicina Interna/educação , Tempo de Internação , Estudos Prospectivos
7.
Br J Biomed Sci ; 77(4): 159-167, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33252323

RESUMO

Each year the British Journal of Biomedical Science publishes a 'What have we learned' editorial designed to introduce readers within the major disciplines of laboratory medicine to developments outside their immediate area. In addition it is designed to inform a wider readership of the advances in the diagnosis and treatment of disease. To this end, in 2020 the journal published 39 articles covering the disciplines within Biomedical Science in the 4 issues comprising volume 77. These included a review of COVID-19 in this issue, 27 original articles, 6 Biomedical Science 'In Brief' and 4 case histories. 27 of the articles involved molecular techniques, with one of these comparing results with a mass spectrometry based method. The preponderance of molecular genetic studies gives us a good idea of the likely future direction of the disciplines.


Assuntos
Pesquisa Biomédica/tendências , Pandemias , Revisão da Pesquisa por Pares/tendências , COVID-19/virologia , Humanos , SARS-CoV-2/patogenicidade
9.
Br J Biomed Sci ; 77(4): 168-184, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32942955

RESUMO

The COVID-19 disease is caused by the SARS-CoV-2 virus, which is highly infective within the human population. The virus is widely disseminated to almost every continent with over twenty-seven million infections and over ninety-thousand reported deaths attributed to COVID-19 disease. SARS-CoV-2 is a single stranded RNA virus, comprising three main viral proteins; membrane, spike and envelope. The clinical features of COVID-19 disease can be classified according to different degrees of severity, with some patients progressing to acute respiratory distress syndrome, which can be fatal. In addition, many infections are asymptomatic or only cause mild symptoms. As there is no specific treatment for COVID-19 there is considerable endeavour to raise a vaccine against SARS-CoV-2, in addition to engineering neutralizing antibody interventions. In the absence of an effective vaccine, movement controls of varying stringencies have been imposed. Whilst enforced lockdown measures have been effective, they may be less effective against the current strain of SARS-CoV-2, the G614 clade. Conversely, other mutations of the virus, such as the Δ382 variant could reduce the clinical relevance of infection. The front runners in the race to develop an effective vaccine focus on the SARS-Co-V-2 Spike protein. However, vaccines that produce a T-cell response to a wider range of SARS-Co-V-2 viral proteins, may be more effective. Population based studies that determine the level of innate immunity to SARS-CoV-2, from prior exposure to the virus or to other coronaviruses, will have important implications for government imposed movement control and the strategic delivery of vaccination programmes.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Pandemias , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/virologia , Humanos , SARS-CoV-2/patogenicidade , Vacinas Virais/uso terapêutico
10.
Bone Joint J ; 101-B(3): 281-287, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30813797

RESUMO

AIMS: The aim of this study was to establish the incidence of developmental dysplasia of the hip (DDH) diagnosed after one-year of age in England, stratified by age, gender, year, and region of diagnosis. PATIENTS AND METHODS: A descriptive observational study was performed by linking primary and secondary care information from two independent national databases of routinely collected data: the United Kingdom Clinical Practice Research Datalink and Hospital Episode Statistics. The study examined all children from 1 January 1990 to 1 January 2016 who had a new first diagnostic code for DDH aged between one and eight years old. RESULTS: The incidence of late-diagnosed DDH was 1.28 per 1000 live births. Within the study population, 754 children were identified with a diagnosis of DDH after one-year of age. Of all late diagnoses, 536 (71.1%) were detected between one to two years of age. There were 608 female patients (80.6%) and 146 male patients (19.4%), giving a female-to-male ratio of 4.2:1. Distribution was evenly spread throughout England. CONCLUSION: The incidence of late-diagnosed DDH has not been reduced from that reported 35 years ago, prior to the introduction of the national selective screening programme for DDH. Cite this article: Bone Joint J 2019;101-B:281-287.


Assuntos
Diagnóstico Tardio/estatística & dados numéricos , Luxação Congênita de Quadril/diagnóstico , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Bases de Dados Factuais , Inglaterra/epidemiologia , Feminino , Luxação Congênita de Quadril/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Triagem Neonatal
11.
Epidemiol Psychiatr Sci ; 29: e17, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30714563

RESUMO

AIMS: The nature of the association between child psychiatric symptoms and adolescent suicide-related thoughts (SRT) and attempts (SA) remains unclear. Our objective was to assess whether child psychiatric symptoms from 6 to 10 years of age mediate the association between exposure to maternal depressive symptoms in childhood and offspring SRT and SA in adolescence. METHODS: A population-based cohort study was constructed by linking all eight cycles from the National Longitudinal Survey of Children and Youth (NLSCY), a nationally representative Canadian panel survey conducted from 1994 to 2009. Self-reported maternal depressive symptoms were measured when offspring were between 0 and 5 years. Maternal-reported child psychiatric symptoms and psychiatric comorbid symptoms were measured from 6 to 10 years, and offspring self-reported SRT and SA were measured between 11 and 19 years. Indirect effects, the effect proportion mediated and their corresponding bootstrapped 95% confidence intervals (CI) were estimated. RESULTS: Hyperactivity and inattention significantly mediated the association between maternal depressive symptoms in childhood and risk of both SRT and SA from 11 to 19 years, where approximately 60% (SRT 95% CI 23-94%; SA 95% CI 27-95%) of this association was explained by hyperactivity and inattention. Psychiatric comorbid symptoms also significantly mediated this relationship and accounted for 50% (95% CI 18-81%) of this association with SA. CONCLUSIONS: Targeting hyperactivity and inattention, and co-occurring psychiatric symptoms in offspring of depressed mothers could reduce risk of SRT, eventual SA and halt progression towards suicide. However, further understanding of comorbid psychiatric symptoms in childhood that most strongly predict adolescent SA is needed.


Assuntos
Comportamento do Adolescente/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno Depressivo/psicologia , Mães/psicologia , Ideação Suicida , Tentativa de Suicídio/psicologia , Adolescente , Adulto , Canadá , Criança , Filho de Pais Incapacitados/psicologia , Filho de Pais Incapacitados/estatística & dados numéricos , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Fatores de Risco , Tentativa de Suicídio/estatística & dados numéricos , Adulto Jovem
12.
Epidemiol Psychiatr Sci ; 28(2): 179-190, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28748774

RESUMO

AIMS: The primary objective of this systematic review was to identify and synthesise analytic studies examining the association between exposure to parental psychopathology in childhood and the nature of subsequent suicide-related thoughts (SRT) and suicide-related behaviour (SRB) (severity of ideation, planned/unplanned attempts/lethality) and to describe the direction, and magnitude of associations. The secondary objective was to determine if the associations from the primary objective differ by the type(s) and timing of parental psychopathology, sex/gender of the parent and child and is mediated by child psychiatric symptoms and family functioning. METHODS: A systematic review was conducted using guidelines from the PRISMA statement. MEDLINE, CINAHL, EMBASE, psycINFO, Web of Science and grey literature sources were searched by two reviewers to March, 2017. Studies were included if they examined any parental psychopathology (Diagnostic and Statistical Manual of Mental Disorders criteria or equivalent) or SRT or SRB and offspring SRT or SRB occurring from birth <25 years of age. RESULTS: Out of 10 231 studies identified, 54 were included for review. Studies were clinically and methodologically heterogeneous with none at low risk of bias (ROB). Nine studies with moderate ROB indicated a significantly increased risk of offspring SRT, suicide attempts (SA) and suicide among those exposed to maternal SA and suicide in childhood or adolescence. In the remaining 45 studies with higher ROB this association persisted. Several studies (67%) did not confirm that the exposure occurred in the offspring's childhood or adolescence. Findings were suggestive of a mediating effect of offspring psychiatric symptoms, however, few studies examined mediation and effect modification of contextual variables. CONCLUSIONS: Offspring exposed to maternal SA are at an increased risk of these same behaviours early in life. Prospective attention to the types and timing of maternal and paternal psychopathology and the intermediate pathways to offspring SRT and SRB onset is needed and could have implications for informing modifiable targets for early intervention and prevention.


Assuntos
Crianças Adultas/psicologia , Filho de Pais Incapacitados/psicologia , Relações Pais-Filho , Pais/psicologia , Ideação Suicida , Tentativa de Suicídio/psicologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Psicopatologia , Fatores Sexuais
13.
Malays J Pathol ; 41(3): 243-251, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31901908

RESUMO

INTRODUCTION: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene. MATERIALS AND METHODS: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies. RESULTS: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent. CONCLUSIONS: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.


Assuntos
Neoplasias da Próstata/genética , Receptores Androgênicos/genética , Idoso , Idoso de 80 Anos ou mais , Androgênios/metabolismo , Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/genética , Regulador Transcricional ERG/genética , Repetições de Trinucleotídeos/genética
14.
Malays J Pathol ; 40(2): 103-110, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30173226

RESUMO

INTRODUCTION: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. METHODS: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. RESULTS: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). CONCLUSION: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Neoplasias da Próstata/patologia , Idoso , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Regulador Transcricional ERG/análise , Regulador Transcricional ERG/biossíntese
15.
Osteoporos Int ; 29(6): 1321-1328, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29479646

RESUMO

In the large UK Biobank population-based cohort, we found that amongst men, but not women, prior fragility fracture was associated with increased risk of admission with ischaemic heart disease. INTRODUCTION: We aimed to investigate the relationship between prior fracture and risk of incident ischaemic cardiovascular events in a UK population-based cohort. METHODS: UK Biobank is a large prospective cohort comprising 502,637 men and women aged 40-69 years, with detailed baseline assessment. History of fracture was self-reported, and details of hospital admissions for ischaemic heart disease (IHD) (ICD-10:I20-I25) were obtained through linkage to UK Hospital Episode Statistics. Cox proportional hazards models were used to investigate the prospective relationships between prior fracture and hospital admission for men and women, controlling for age, BMI, smoking, alcohol, educational level, physical activity, systolic blood pressure, calcium and vitamin D use, ankle spacing-width, heel BUA and HRT use (women). RESULTS: Amongst men, a fragility fracture (hip, spine, wrist or arm fracture resulting from a simple fall) within the previous 5 years was associated with a 35% increased risk of IHD admission (fully adjusted HR 1.35; 95%CI 1.00, 1.82; p = 0.047), with the relationship predominantly driven by wrist fractures. Associations with hospitalisation for angina in men were similar in age-adjusted models [HR1.54; 95%CI: 1.03, 2.30), p = 0.037], but did not remain statistical significant after full adjustment [HR 1.64; 95%CI: 0.88, 3.07); p = 0.121]. HRs for admission with angina were lower in women, and neither age- nor fully adjusted relationships attained statistical significance. CONCLUSIONS: Prior fragility fracture is an independent risk factor for incident ischaemic cardiovascular events in men. Further work may clarify whether this association is causal or represents shared risk factors, but these findings are likely to be of value in risk assessment of both osteoporosis and cardiovascular disease.


Assuntos
Isquemia Miocárdica/epidemiologia , Fraturas por Osteoporose/epidemiologia , Adulto , Idoso , Angina Pectoris/epidemiologia , Angina Pectoris/etiologia , Bancos de Espécimes Biológicos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Isquemia Miocárdica/etiologia , Fraturas por Osteoporose/complicações , Medição de Risco/métodos , Fatores Sexuais , Reino Unido/epidemiologia
16.
J Child Orthop ; 11(6): 440-447, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29263756

RESUMO

Purpose: To determine the prevalence of osteonecrosis (ON) in children following treatment of acute lymphoblastic leukaemia (ALL), characterise these cases and review treatment methods. Methods: All children diagnosed and treated for ALL between 01 January 2003 and 31 December 2013 at our centre were retrospectively reviewed. Logistic regression was used to investigate risk factors for ON occurrence. Results: Of 235 children treated for ALL, 48/235 (20.4%) children suffered musculoskeletal symptoms necessitating radiological investigation. A total of 13 (5.5%) had MRI-diagnosed ON, with a median diagnosis time of 12 months (interquartile range 10 to 14) following initiation of chemotherapy.ON affected 40 joints in 13 children. The most commonly involved joints were hips (14 joints in eight patients) and knees (12 joints in seven patients).Older age at ALL diagnosis was associated with significantly increased risk of development of ON per year (odds ratio 1.35, 95% confidence interval 1.17 to 1.57, p < 0.001).Eight children underwent at least one surgical intervention. Joint arthroplasty was undertaken in nine joints of four children at a mean age of 18.3 years. All patients who underwent hip arthroplasty had previously received core decompression, with a mean time of 27.8 months (18 to 33) between treatments. Conclusions: ON is a significant complication of ALL treatment. Our results suggest risk stratification for development of ON by age, and targeted monitoring of high-risk joints is possible. ON treatment is varied with little evidence base.

17.
Br J Biomed Sci ; 74(4): 176-180, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28705139

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death. Approximately 2-16% of NSCLC patients with wild-type epidermal growth factor receptor (EGFR) harbour anaplastic lymphoma kinase (ALK) mutations. Both EGFR and ALK mutations occur most commonly in Asian patients with NSCLC. As targeted therapy is available for NSCLC patients with these mutations, it is important to establish reliable assays and testing strategies to identify those most likely to benefit from this therapy. MATERIALS AND METHODS: Patients diagnosed with adenocarcinoma of the lung between 2010 and 2014 were tested for EGFR mutations. Of these, 92 cases were identified as EGFR wild type and suitable candidates for ALK testing utilising immunohistochemistry and the rabbit monoclonal antibody D5F3. The reliability of the IHC was confirmed by validating the results against those achieved by fluorescence in situ hybridisation (FISH) to detect ALK gene rearrangements. RESULTS: Twelve (13%) cases were positive for ALK expression using immunohistochemistry. Of the 18 evaluable cases tested by FISH, there was 100% agreement with respect to ALK rearrangement/ALK expression between the assays, with 11 cases ALK negative and 7 cases ALK positive by both assays. ALK tumour expression was significantly more common in female compared to male patients (29.6% vs. 6.2%, P < 0.001), detected exclusively in patients that had never smoked (P < 0.001) and more frequently in metastases (22.7%) than in primary tumours (10%) (P = 0.047). CONCLUSIONS: Detection of ALK expression by IHC is reliable and the most practical way of identifying NSCLC patients likely to benefit from crizotinib treatment.


Assuntos
Adenocarcinoma de Pulmão/enzimologia , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Mutação/genética , Adenocarcinoma de Pulmão/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Br J Anaesth ; 118(6): 938-946, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575332

RESUMO

BACKGROUND.: Dynamic arterial elastance (Ea dyn ), the relationship between pulse pressure variation (PPV) and stroke volume variation (SVV), has been suggested as a functional assessment of arterial load. The aim of this study was to evaluate the impact of arterial load changes during acute pharmacological changes, fluid administration, and haemorrhage on Ea dyn . METHODS.: Eighteen anaesthetized, mechanically ventilated New Zealand rabbits were studied. Arterial load changes were induced by phenylephrine ( n =9) or nitroprusside ( n =9). Thereafter, animals received a fluid bolus (10 ml kg -1 ), followed by stepwise bleeding (blood loss: 15 ml kg -1 ). The influence of arterial load and cardiac variables on PPV, SVV, and Ea dyn was analysed using a linear mixed-effects model analysis. RESULTS.: After phenylephrine infusion, mean ( sd ) Ea dyn decreased from 0.89 (0.14) to 0.49 (0.12), P <0.001; whereas after administration of nitroprusside, Ea dyn increased from 0.80 (0.23) to 1.28 (0.21), P <0.0001. Overall, the fluid bolus decreased Ea dyn [from 0.89 (0.44) to 0.73 (0.35); P <0.01], and haemorrhage increased it [from 0.78 (0.23) to 0.95 (0.26), P =0.03]. Both PPV and SVV were associated with similar arterial factors (effective arterial elastance, arterial compliance, and resistance) and heart rate. Furthermore, PPV was also related to the acceleration and peak velocity of aortic blood flow. Both arterial and cardiac factors contributed to the evolution of Ea dyn throughout the experiment. CONCLUSIONS.: Acute modifications of arterial load induced significant changes on Ea dyn ; vasodilatation increased Ea dyn , whereas vasoconstriction decreased it. The Ea dyn was associated with both arterial load and cardiac factors, suggesting that Ea dyn should be more properly considered as a ventriculo-arterial coupling index.


Assuntos
Artérias/fisiologia , Animais , Artérias/efeitos dos fármacos , Débito Cardíaco , Complacência (Medida de Distensibilidade) , Circulação Coronária/efeitos dos fármacos , Circulação Coronária/fisiologia , Elasticidade , Hidratação , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hemorragia/fisiopatologia , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Coelhos , Resistência Vascular , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
19.
Intensive care med ; 43(3)Mar. 2017.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-948600

RESUMO

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy wasdeveloped at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroupsand among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.(AU)


Assuntos
Humanos , Choque Séptico/tratamento farmacológico , Sepse/tratamento farmacológico , Planejamento de Assistência ao Paciente , Respiração Artificial , Vasoconstritores/uso terapêutico , Calcitonina/uso terapêutico , Avaliação Nutricional , Doença Crônica/tratamento farmacológico , Terapia de Substituição Renal , Hidratação/métodos , Antibacterianos/administração & dosagem
20.
Br J Anaesth ; 117(5): 610-616, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27799175

RESUMO

BACKGROUND: Several guidelines have been published to facilitate implementation of patient blood management (PBM). This study was performed to evaluate clinical practices in PBM. METHODS: An online survey based on the guidelines for the management of severe perioperative bleeding from the European Society of Anaesthesiology (ESA) was conducted among ESA members. We assessed characteristic data of participating physicians, preoperative assessment of bleeding risk and anaemia, intraoperative transfusion practices, specific pharmacologic treatment of significant bleeding, and clinical use of PBM algorithms. Data distributions for five European regions and the workplace and experience of physicians were analysed using a χ2 test. RESULTS: We received 706 fully completed surveys from physicians in 57 countries. Most (99%) respondents were anaesthetists or intensive care physicians, and 68% worked at university or university-affiliated hospitals. A standardised bleeding history before surgery is routinely obtained by 48% of physicians. When bleeding history is negative, 55% of physicians routinely order preoperative coagulation testing. Only 24% of physicians timely assess patients at risk of bleeding during surgery for anaemia before elective surgery. When anaemia is diagnosed, 38% of physicians routinely investigate its cause. The rate of routinely performed targeted haemostatic interventions with fibrinogen, vitamin K or prothrombin complex, and tranexamic acid was 60%, 52%, and 54%, respectively. Algorithms to guide PBM are used by 62% of physicians. Results varied between geographic regions. CONCLUSIONS: Major deficits exist in the use of recommended PBM among anaesthetists, indicating an opportunity to improve clinical standards.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Hemostáticos/uso terapêutico , Assistência Perioperatória/métodos , Padrões de Prática Médica/estatística & dados numéricos , Europa (Continente) , Hemostasia , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...