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2.
Hum Reprod Open ; 2022(2): hoac019, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35591921

RESUMO

STUDY QUESTION: Is the Patient Health Questionnaire-8 (PHQ-8) a valid and reliable measure of depression in first-time mothers who conceived via ART? SUMMARY ANSWER: The results from this study provide initial support for the reliability and validity of the PHQ-8 as a measure of depression in mothers who have conceived using ART. WHAT IS KNOWN ALREADY: Women who achieved a clinical pregnancy using ART experience many stressors and may be at an increased risk of depression. The PHQ-8 is a brief measure designed to detect the presence and severity of depressive symptoms. It has been validated in many populations; however, it has not been validated for use in this population. STUDY DESIGN SIZE DURATION: This is a cross-sectional study of 171 first-time mothers in the USA, recruited through Amazon's Mechanical Turk (MTurk). PARTICIPANTS/MATERIALS SETTING METHODS: The reliability of the PHQ-8 was measured through a Cronbach's alpha, the convergent validity was measured through the correlation between the PHQ-8 and the Generalized Anxiety Disorder-7 (GAD-7) measure of anxiety symptoms, and the structural validity was measured through a Confirmatory Factor Analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The Cronbach's alpha for the total PHQ-8 was acceptable (α = 0.922). The correlation between the PHQ-8 and the GAD-7 was large (r = 0.88) indicating good convergent validity. Ultimately, a bifactor model provided the best model fit ( χ 2 (13) = 23.8, P = 0.033; Comparative Fit Index = 0.987; Root Mean Square Error of Approximation = 0.07, Tucker-Lewis Index = 0.972). LIMITATIONS REASONS FOR CAUTION: The results are limited by: the predominantly white and well-educated sample, a lack of causation between the use of artificial reproductive technology and depressive symptoms, including mothers with children up to 5 years old, convergent validity being based on associations with a related construct instead of the same construct, lack of test-retest reliability, divergent validity and criterion-related validity, data collected through MTurk, and the fact that the measures used were all self-report and therefore may be prone to bias. WIDER IMPLICATIONS OF THE FINDINGS: Consistent with previous literature, a bifactor model for the PHQ-8 was supported. As such, when assessing depression in first-time mothers who conceived via ART, using both the PHQ-8 total score and subdomain scores may yield the most valuable information. The results from this study provide preliminary support for the reliability and validity of the PHQ-8 as a measure of depression in first-time mothers who conceived using ART. STUDY FUNDING/COMPETING INTERESTS: No specific funding was used for the completion of this study. Throughout the study period and manuscript preparation, the authors were supported by the department funds at Baylor University. The authors declare that they have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

3.
Cancer Chemother Pharmacol ; 88(2): 307-312, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33944970

RESUMO

PURPOSE: This study aimed to provide a better understanding of the impact of paclitaxel chemotherapy on breath alcohol in an Irish population. METHODS: Patients attending the Oncology Day Unit at Beaumont Hospital were invited to participate on the day of their treatment. The brand of paclitaxel used was Actavis Pharma Inc and contained 6 mg/mL paclitaxel in 50% Ethanol/ 50% Cremophor EL. Breath alcohol concentration was measured using the AlcoSense ™ Breathalyser on three separate visits. The primary end-point was the number of patients who were above the legal threshold for drink driving in Ireland. RESULTS: In total, 50 patients were recruited. 36 (68%) were female. The most common diagnosis was breast cancer (56%). Ten (20%) patients had metastatic disease and 4 (8%) had liver metastases. The mean paclitaxel dose administered was 118 mg. The mean amount of ethanol infused was 7.7 g. 27 patients had a detectable breath alcohol level on at least one visit. The mean breath alcohol concentration was 2 mcg/100 mL or 0.02 mg/L of breath. The maximum concentration of ethanol in exhaled breath was 11 mcg/100 mL or 0.11 mg/L which is 50% of the statutory limit for drink driving in Ireland. A weak correlation was observed between ethanol concentration in exhaled breath and the total amount of ethanol administered. Although no patient exceeded the general limit for drink driving in Ireland, three (6%) participants had a breath alcohol concentration above the threshold for professional, learner or novice drivers. CONCLUSION: Although definitive conclusions are limited by relatively small numbers, it seems unlikely that weekly paclitaxel infusions pose any significant risk to patients driving.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Etanol/metabolismo , Paclitaxel/metabolismo , Adulto , Idoso , Antineoplásicos Fitogênicos/uso terapêutico , Testes Respiratórios/métodos , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Paclitaxel/uso terapêutico , Estudos Prospectivos
4.
Breast Cancer Res Treat ; 187(3): 635-645, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33983492

RESUMO

BACKGROUND: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. METHODS: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. RESULTS: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). CONCLUSIONS: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Linfócitos , Linfócitos do Interstício Tumoral , Prognóstico , Receptor ErbB-2/genética
5.
J Hosp Infect ; 101(1): 1-10, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30092292

RESUMO

BACKGROUND: Intracavity medical devices (ICMDs) are used in a wide variety of healthcare settings. The approach to their decontamination and the resources available also differ widely. Their potential for infection transmission is considerable. AIM: To produce a comprehensive risk assessment-based approach to the decontamination of ICMDs, accompanied by an adaptable audit tool.


Assuntos
Descontaminação/métodos , Transmissão de Doença Infecciosa/prevenção & controle , Equipamentos e Provisões , Humanos , Sociedades Científicas
6.
J Thromb Haemost ; 2018 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-29802795

RESUMO

Essentials Eisenmenger syndrome is characterised by thrombotic and hemorrhagic risks of unclear aetiology. Calibrated automated thrombography was used to assess these coagulation derangements. Platelet activity supported abnormalities in procoagulant and anticoagulant pathway function. Endothelin-1 antagonism appeared to ameliorate these derangements. SUMMARY: Aims The mechanisms underlying the competing thrombotic and hemorrhagic risks in Eisenmenger syndrome are poorly understood. We aimed to characterize derangements of blood coagulation and to assess the effect of dual endothelin-1 receptor antagonism in modulating hemostasis in this rare disorder. Methods In a 10-month recruitment period at a tertiary cardiology referral center, during which time there were over 14 000 outpatient consultations, consecutive subjects with Eisenmenger syndrome being considered for macitentan therapy (n = 9) and healthy volunteers (n = 9) were recruited. Plasma thrombin generation in platelet-rich and platelet-poor plasma was assessed by calibrated automated thrombography prior to and following therapy. Results Median peak plasma thrombin generation was higher in platelet-rich plasma obtained from Eisenmenger syndrome subjects relative to controls (median peak thrombin [25th-75th percentile]: 228.3 [206.5-258.6] nm vs. 169.9 [164.3-215.8] nm), suggesting a critical mechanistic role for platelets in supporting abnormal hypercoagulability in Eisenmenger syndrome. Abnormal enhanced sensitivity to the anticoagulant activity of activated protein C was also observed in platelet-rich plasma in Eisenmenger syndrome, suggesting that derangements of platelet activity may influence the activity of anticoagulant pathways in a manner that might promote bleeding in this disease state. Following 6 months of macitentan therapy, attenuations in the derangements in both procoagulant and anticoagulant pathways were observed. Conclusions Abnormal platelet activity contributes to derangements in procoagulant and anticoagulant pathways in Eisenmenger syndrome. Therapies targeting the underlying vascular pathology appear to ameliorate these derangements and may represent a novel strategy for the management of the competing prothrombotic and hemorrhagic tendencies in this disorder.

7.
Sci Rep ; 6: 39283, 2016 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-28008932

RESUMO

Sleep is modulated by several factors, including sex, age, and chronotype. It has been hypothesised that contemporary urban populations are under pressure towards shorter sleep duration and poorer sleep quality. Baependi is a small town in Brazil that provides a window of opportunity to study the influence of sleep patterns in a highly admixed rural population with a conservative lifestyle. We evaluated sleep characteristics, excessive daytime sleepiness, and chronotype using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Morningness-Eveningness Questionnaire questionnaires, respectively. The sample consisted of 1,334 subjects from the Baependi Heart study (41.5% male; age: 46.5 ± 16.2 y, range: 18-89 years). Average self-reported sleep duration was 07:07 ± 01:31 (bedtime 22:32 ± 01:27, wake up time: 06:17 ± 01:25 hh:min), sleep quality score was 4.9 + 3.2, chronotype was 63.6 ± 10.8 and daytime sleepiness was 7.4 ± 4.8. Despite a shift towards morningness in the population, chronotype remained associated with reported actual sleep timing. Age and sex modulated the ontogeny of sleep and chronotype, increasing age was associated with earlier sleep time and shorter sleep duration. Women slept longer and later, and reported poorer sleep quality than men (p < 0.0001). This study provides indirect evidence in support of the hypothesis that sleep timing was earlier prior to full urbanisation.


Assuntos
Higiene do Sono , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Fatores Sexuais , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
8.
Evid Based Preclin Med ; 3(1): e00015, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-29214041

RESUMO

The increasing prevalence of Alzheimer's disease (AD) poses a considerable socio-economic challenge. Decades of experimental research have not led to the development of effective disease modifying interventions. A deeper understanding of in vivo research might provide insights to inform future in vivo research and clinical trial design. We therefore performed a systematic review and meta-analysis of interventions tested in transgenic mouse models of AD. We searched electronically for publications testing interventions in transgenic models of AD. We extracted data for outcome, study characteristics and reported study quality and calculated summary estimates of efficacy using random effects meta-analysis. We identified 427 publications describing 357 interventions in 55 transgenic models, involving 11,118 animals in 838 experiments. Of concern, reported study quality was relatively low; fewer than one in four publications reported the blinded assessment of outcome or random allocation to group and no study reported a sample size calculation. Additionally, there were few data for any individual intervention-only 16 interventions had outcomes described in 5 or more publications. Finally, "trim and fill" analyses suggested one in seven pathological and neurobehavioural experiments remain unpublished. Given these historical weaknesses in the in vivo modelling of AD in transgenic animals and the identified risks of bias, clinical trials that are based on claims of efficacy in animals should only proceed after a detailed critical appraisal of those animal data.

10.
Andrology ; 3(6): 1165-72, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26452447

RESUMO

Little is known about how total testosterone and estradiol-17ß influence lower urinary tract symptoms (LUTS) in men with benign prostatic hypertrophy (BPH). We analyzed data from a subset of men aged ≥18 years randomized to tadalafil 5 mg once-daily or placebo who had ≥6 month history of LUTS and an International Prostate Symptom Score (IPSS)≥13 enrolled in one of three randomized, placebo-controlled tadalafil clinical trials (N = 958). Three specific aims were addressed, as follows: (i) To characterize enrolled men by treatment randomization and testosterone level; (ii) to assess cross-sectional associations of estradiol-17ß, testosterone, and LUTS prior to treatment with tadalafil; and, (iii) to assess longitudinal associations between baseline estradiol-17ß and testosterone and improvements or worsening of LUTS during a 12-week period of tadalafil or placebo administration. LUTS were assessed by total IPSS, IPSS voiding sub-score (IPSS-V) and IPSS storage sub-score (IPSS-S) for cross-sectional analyses, and change in total IPSS (ΔIPSS), ΔIPSS-V, and ΔIPSS-S between baseline and 12-week visit for longitudinal analyses. Correlation analyses and linear regression examined associations. Baseline testosterone was not significantly associated with IPSS. In contrast, estradiol-17ß was inversely correlated with IPSS (r = -0.08; p < 0.05) and IPSS-S (r = -0.14; p < 0.05). Tadalafil treatment resulted in greater IPSS improvements in men with lower baseline estradiol-17ß versus those with higher baseline estradiol-17ß. Lower baseline estradiol-17ß was significantly associated with modestly improved ΔIPSS-V (p = 0.04) and Δtotal IPSS (p = 0.05) but not with ΔIPSS-S, following treatment which may substantiate the role of bladder dysfunction because of nerve and smooth muscle changes in the bladder in addition to benign prostatic enlargement in LUTS. Circulating baseline testosterone did not predict ΔIPSS. Men with lower baseline estradiol-17ß levels showed greater responsiveness to tadalafil 5 mg treatment than those with higher baseline estradiol-17ß levels when responsiveness was measured using total IPSS and IPSS-V.


Assuntos
Estradiol/sangue , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Tadalafila/uso terapêutico , Testosterona/sangue , Idoso , Biomarcadores/sangue , Estudos Transversais , Bases de Dados Factuais , Humanos , Estudos Longitudinais , Sintomas do Trato Urinário Inferior/sangue , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Hiperplasia Prostática/sangue , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento
11.
J Thromb Haemost ; 13(11): 2021-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26334448

RESUMO

BACKGROUND: Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests. OBJECTIVES: The primary objective of this study was to measure standard plasma coagulation tests and thrombin generation in very premature infants compared with term infants. The secondary objective was to evaluate whether an association existed between coagulation indices and intraventricular hemorrhage (IVH). PATIENTS/METHODS: Cord and peripheral blood of neonates < 30 weeks gestational age (GA) was drawn at birth, on days 1 and 3 and fortnightly until 30 weeks corrected gestational age. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and coagulation factor levels were measured and tissue factor-stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates. RESULTS: One hundred and sixteen infants were recruited. Median (range) GA was 27.7 (23.7-29.9) weeks and mean (SD) birth weight was 1020 (255) g. Median (5th-95th percentile) day 1 PT, APTT and fibrinogen were 17.5 (12.7-26.6) s, 78.7 (48.7-134.3) s and 1.4 (0.72-3.8) g L(-1) , respectively. No difference in endogenous thrombin potential between preterm and term plasma was observed, where samples were available. Levels of coagulation factors II, VII, IX and X, protein C, protein S and antithrombin were reduced in preterm compared with term plasma. Day 1 APTT and PT were not associated with IVH. CONCLUSION: In the largest cross-sectional study to date of very preterm infants, typical ranges for standard coagulation tests were determined. Despite long clotting times, thrombin generation was observed to be similar in very preterm and term infants.


Assuntos
Testes de Coagulação Sanguínea , Sangue Fetal/fisiologia , Recém-Nascido Prematuro/sangue , Fatores de Coagulação Sanguínea/análise , Transfusão de Componentes Sanguíneos , Ventrículos Cerebrais , Estudos Transversais , Feminino , Fibrinogênio/análise , Idade Gestacional , Transtornos Hemorrágicos/sangue , Transtornos Hemorrágicos/etiologia , Transtornos Hemorrágicos/terapia , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Terapia Intensiva Neonatal , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/etiologia , Masculino , Tempo de Tromboplastina Parcial , Estudos Prospectivos , Tempo de Protrombina , Proteínas Recombinantes/farmacologia , Padrões de Referência , Trombina/biossíntese , Tromboplastina/farmacologia , Vitamina K/uso terapêutico
12.
Int J Clin Pract ; 69(11): 1316-25, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26215544

RESUMO

OBJECTIVE: The objective of this study was to investigate rural/urban and socio-demographic disparities in lower urinary tract symptoms and benign prostatic hyperplasia (LUTS/BPH) in a nationally representative population of men. METHODS: Data on men age ≥40 years (N = 4,492) in the 2001-2008 National Health and Nutrition Examination Surveys were analysed. Self-report of physician-diagnosed enlarged prostate and/or BPH medication use defined recognised LUTS/BPH. Urinary symptoms without BPH diagnosis/medications defined unrecognised LUTS/BPH. Rural-Urban Commuting Area Codes assessed urbanisation. Unadjusted and multivariable associations (odds ratios (OR)) between LUTS/BPH and covariates were calculated using logistic regression. RESULTS: Recognised and unrecognised LUTS/BPH weighted-prevalence estimates were 16.5% and 9.6%. There were no significant associations between LUTS/BPH and rural/urban status. Significant predisposing factors for increased adjusted odds of recognised and unrecognised LUTS/BPH included age, hypertension (OR=1.4;1.4), analgesic use (OR=1.4;1.4) and PSA level >4 ng/mL (OR=2.3;1.9) when adjusted for rural/urban status, race, education, income, alcohol, health insurance, health care and proton pump inhibitor (PPI) use (all p ≤ 0.1). Restricting to urban men only (N = 3,371), healthcare use (≥4visits/year) and PPI's increased adjusted odds of recognised LUTS/BPH (OR=2.0;1.6); no health insurance and

Assuntos
Disparidades nos Níveis de Saúde , Sintomas do Trato Urinário Inferior/epidemiologia , Hiperplasia Prostática/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Idoso , Envelhecimento , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Fatores de Risco , Fatores Socioeconômicos , Estados Unidos/epidemiologia
13.
Evid Based Preclin Med ; 2(1): e00010, 2015 08.
Artigo em Inglês | MEDLINE | ID: mdl-27570629

RESUMO

Despite many efforts by the research community, Alzheimer's disease (AD) is still an incurable neurodegenerative condition that affects an estimated 44 million individuals worldwide and this figure is expected to increase to 135 million by the year 2050. As the research community currently reflects on previous endeavours, it is essential that we maximize the use of existing knowledge to inform future trials in the field. This article describes the development of a systematically identified data set relating to over 300 interventions tested in over 10,000 animals. The data set includes cohort-level information for six structural outcomes and six behavioural assessments. We encourage others to use this dataset to inform the design of future animal experiments modelling AD and to promote effective translation to human health.

14.
Pediatr Obes ; 10(5): 345-52, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25405952

RESUMO

BACKGROUND: In adolescents the temporal directionality to the asthma and adiposity association remains unclear. Asthma may be a consequence of obesity; however, asthma may increase adiposity. OBJECTIVES: This study aimed to assess the associations between (i) baseline weight status and subsequent asthma and (ii) baseline asthma and subsequent weight status after 4 and 11 years of follow-up (N = 1543 and N = 1596, respectively) using data from three, sequentially enrolled population-based surveys of Norwegians aged 12-30 years from 1995 to 2008. METHODS: Weight status was defined as general (body mass index) or abdominal (waist circumference) underweight, normal weight, overweight or obesity. Self-report physician-diagnosed asthma defined asthma status. RESULTS: Over the longitudinal 11-year follow-up, baseline generally overweight or abdominally obese adolescents had increased risk of asthma. Likewise, baseline asthmatics had increased risk of general overweight or abdominal obesity. After sex stratification, these associations were stronger in males. Generally (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.32, 2.73) or abdominally (OR 1.66; 95% CI 1.13, 2.44) overweight males were at increased risk of asthma. Baseline asthmatic males were also at increased risk of general (OR 2.14; 95% CI 1.54, 2.98) and abdominal (OR 1.77; 95% CI 1.27, 2.47) overweight. CONCLUSIONS: Among Norwegian adolescents, a bidirectional association of asthma and adiposity was observed in males. Each baseline condition increased the risk of the other condition over time. No association was observed in females.


Assuntos
Asma/fisiopatologia , Obesidade Abdominal/fisiopatologia , Adiposidade , Adolescente , Adulto , Asma/epidemiologia , Asma/etiologia , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Noruega/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Razão de Chances , Sobrepeso , Circunferência da Cintura , Adulto Jovem
15.
J Neurosci Methods ; 221: 92-102, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24099992

RESUMO

Meta-analyses of data from human studies are invaluable resources in the life sciences and the methods to conduct these are well documented. Similarly there are a number of benefits in conducting meta-analyses on data from animal studies; they can be used to inform clinical trial design, or to try and explain discrepancies between preclinical and clinical trial results. However there are inherit differences between animal and human studies and so applying the same techniques for the meta-analysis of preclinical data is not straightforward. For example preclinical studies are frequently small and there is often substantial heterogeneity between studies. This may have an impact on both the method of calculating an effect size and the method of pooling data. Here we describe a practical guide for the meta-analysis of data from animal studies including methods used to explore sources of heterogeneity.


Assuntos
Modelos Animais de Doenças , Metanálise como Assunto , Projetos de Pesquisa , Animais , Humanos
16.
Evid Based Preclin Med ; 1(1): e00006, 2014 12.
Artigo em Inglês | MEDLINE | ID: mdl-27668084

RESUMO

BACKGROUND: The development of therapeutics is often characterized by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in glioma. We tested the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of gene therapy in experimental glioma. METHOD: We systematically identified studies testing gene therapy in rodent glioma models by searching three online databases. The number of animals treated and median survival were extracted and studies graded using a quality checklist. We calculated median survival ratios and used random effects meta-analysis to estimate efficacy. We explored effects of study design and quality and searched for evidence of publication bias. RESULTS: We identified 193 publications using gene therapy in experimental glioma, including 6,366 animals. Overall, gene therapy improved median survival by a factor of 1.60 (95% CI 1.53-1.67). Study quality was low and the type of gene therapy did not account for differences in outcome. Study design characteristics accounted for a significant proportion of between-study heterogeneity. We observed similar findings in a data subset limited to the most common gene therapy. CONCLUSION: As the dysregulation of key molecular pathways is characteristic of gliomas, gene therapy remains a promising treatment for glioma. Nevertheless, we have identified areas for improvement in conduct and reporting of studies, and we provide a basis for sample size calculations. Further work should focus on genes of interest in paradigms recapitulating human disease. This might improve the translation of such therapies into the clinic.

17.
Br J Cancer ; 108(1): 64-71, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23321511

RESUMO

BACKGROUND: Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been established as first-line chemotherapy. We investigate the role of in vivo glioma models in predicting clinical efficacy. METHODS: We searched three online databases to systematically identify publications testing temozolomide in animal models of glioma. Median survival and number of animals treated were extracted and quality was assessed using a 12-point scale; random effects meta-analysis was used to estimate efficacy. We analysed the impact of study design and quality and looked for evidence of publication bias. RESULTS: We identified 60 publications using temozolomide in models of glioma, comprising 2443 animals. Temozolomide prolonged survival by a factor of 1.88 (95% CI 1.74-2.03) and reduced tumour volume by 50.4% (41.8-58.9) compared with untreated controls. Study design characteristics accounted for a significant proportion of between-study heterogeneity, and there was evidence of a significant publication bias. CONCLUSION: These data reflect those from clinical trials in that temozolomide improves survival and reduces tumour volume, even after accounting for publication bias. Experimental in vivo glioma studies of temozolomide differ from those of other glioma therapies in their consistent efficacy and successful translation into clinical medicine.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Glioma/tratamento farmacológico , Animais , Dacarbazina/uso terapêutico , Modelos Animais de Doenças , Camundongos , Ratos , Análise de Sobrevida , Temozolomida , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Food Prot ; 75(2): 328-40, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22289594

RESUMO

A great variety of fruits and vegetables are available in the United States. These items are produced in various geographic regions by a diverse industry. Produce has been increasingly identified as a vehicle for disease outbreaks. Changes in consumption may explain this increase, but analyses of produce consumption are limited. Comprehensive assessments of the public health risks associated with produce depend on quantitative consumption data, including the population fractions and subgroups of consumers, the quantities consumed by these individuals, and the processing that occurs before consumption. Here, we provide an analysis of nationally representative consumption estimates by estimating consumption frequencies, serving sizes, and processing forms for a variety of produce commodities based on 1999 through 2006 data from "What We Eat in America," the dietary interview component of the National Health and Nutrition Examination Survey performed by the National Center for Health Statistics. Consumption patterns for fresh and heat-treated produce were assessed, compared with U.S. food availability estimates from the U.S. Department of Agriculture Economic Research Service (ERS), and combined with ERS data on temporal trends in food availability and nondomestic produce origins. To identify high-consuming population subgroups, we explored consumer habits and demographic predictors of fresh produce consumption (data available at www.foodrisk.org). Our analysis of common outbreak vehicles revealed limited temporal changes in food availability but frequent consumption as fresh commodities. In addition to providing quantitative consumption estimates for risk assessments, our data clearly show that produce consumption differs among fruits and vegetables, fresh and heat-treated foods, and demographic subgroups. These results are valuable for risk assessments and outbreak investigations and allow targeting of risk communication or interventions to those individuals at greatest risk.


Assuntos
Comportamento Alimentar , Contaminação de Alimentos/análise , Frutas/microbiologia , Verduras/microbiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise por Conglomerados , Demografia , Abastecimento de Alimentos/estatística & dados numéricos , Humanos , Técnicas In Vitro , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Medição de Risco , Estados Unidos , Adulto Jovem
20.
Breast Cancer Res Treat ; 130(3): 975-80, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21769659

RESUMO

Evidence suggests that certain reproductive factors are more strongly associated with the incidence of lobular than of ductal breast cancer. The mechanisms influencing breast cancer incidence histology may also affect survival. Women with invasive breast cancer (N = 22,302) diagnosed during 1986-2005 were enrolled in a series of population-based studies in three US states. Participants completed telephone interviews regarding reproductive exposures and other breast cancer risk factors. Histologic subtype was obtained from state cancer registries. Vital status and cause of death were determined through December 2006 using the National Death Index. Women were followed for 9.8 years on average with 3,050 breast cancer deaths documented. Adjusted hazard rate ratios (HR) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazards regression models for breast cancer-specific and all-cause mortality. Parity was inversely associated with breast cancer-specific mortality (P (Trend) = 0.002). Associations were similar though attenuated for all-cause mortality. In women diagnosed with ductal breast cancer, a 15% reduction in breast cancer-specific mortality was observed in women with five or more children when compared to those with no children (HR = 0.85, 95% CI: 0.73-1.00). A similar inverse though non-significant association was observed in women with lobular subtype (HR = 0.70, 95% CI: 0.43-1.14). The trend did not extend to mixed ductal-lobular breast cancer. Age at first birth had no consistent relationship with breast cancer-specific or all-cause mortality. We found increasing parity reduced mortality in ductal and lobular breast cancer. The number of full-term births, rather than age at first birth, has an effect on both breast cancer-specific and overall mortality.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , História Reprodutiva , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
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