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1.
Anesthesiol Clin ; 37(3): 411-422, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31337475

RESUMEN

The decision to offer surgery to an older adult with medical comorbidities involves candid conversations between the surgeon, patient, and caregivers. Tools are available to physicians that facilitate patient empowerment. Beyond short-term risks, the conversation should include the potential for institutional discharge, functional and cognitive decline, and longer term mortality.

4.
Hum Gene Ther Clin Dev ; 30(2): 57-66, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30860398

RESUMEN

General safety and toxicology assessments supporting in vivo lentiviral vector-based therapeutic development are sparse. We have previously demonstrated the efficacy of a lentiviral vector expressing fumarylacetoacetate hydrolase (LV-FAH) to cure animal models of hereditary tyrosinemia type 1. Therefore, we performed a complete preclinical toxicological evaluation of LV-FAH, in a large cohort (n = 20/group) of wildtype mice and included matched groups of N-nitrosodiethylamine/carbon tetrachloride (DEN/CCl4)-induced liver injury mice to assess specific toxicity in fibrotic liver tissue. Mice receiving LV-FAH alone (109 TU/mouse) or in combination with DEN/CCl4 presented clinically similar to control animals, with only slight reductions in total body weight gains over the study period (3.2- to 3.7-fold vs. 4.2-fold). There were no indications of toxicity attributed to administration of LV-FAH alone over the duration of this study. The known hepatotoxic combination of DEN/CCl4 induced fibrotic liver injury, and co-administration with LV-FAH was associated with exaggeration of some findings such as an increased liver:body weight ratio and progression to focal hepatocyte necrosis in some animals. Hepatocellular degeneration/regeneration was present in DEN/CCl4-dosed animals regardless of LV-FAH as evaluated by Ki-67 immunohistochemistry and circulating alpha fetoprotein levels, but there were no tumors identified in any tissue in any dose group. These data demonstrate the inherent safety of LV-FAH and support broader clinical development of lentiviral vectors for in vivo administration.

5.
Microb Pathog ; 128: 396-404, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30660737

RESUMEN

BACKGROUND: Gastric fluid pH serves an important function as an ecological filter to kill unwanted microbial taxa that would otherwise colonise the intestines, thereby shaping the diversity and composition of microbial communities found in the gut. The typical American-based diet causes the gastric pH to increase to pH 4 to 5, and it takes ∼2 h to return to pH 1.5 (normal). This window of increased gastric pH may allow potential pathogens to negotiate the hostile environment of the stomach. Another factor to consider is that in developing countries many people experience hypochlorhydria related to malnutrition and various gastric diseases. Enteropathogenic E. coli (EPEC) is a leading cause of infantile diarrhoea and has a high incidence in the developing world. The aim of this study was to assess the survival and recovery of non-acid adapted EPEC exposed to simulated gastric fluid (SGF) over a period of 180 min. RESULTS: EPEC were grown in nutrient-rich medium and acid challenged in SGF at pH 1.5, 2.5, 3.5 and 4.5. Culturability was evaluated using a standard plate count method, and metabolic viability was assessed via cellular energy (adenosine triphosphate [ATP] assay) and respiratory activity (3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide [XTT] assay), and recovery and proliferation by means of optical density in liquid cultures. Sampling was performed at 0, 30, 60, 120, and 180 min post-SGF exposure. The results of this study showed that EPEC is remarkably acid resistant and was able to survive a simulated gastric environment for up to 3 h (180 min) at various pH (1.5, 2.5, 3.5, and 4.5). EPEC was culturable at all pH (1.5, 2.5, 3.5 and 4.5) at the higher inoculum size of 5.4-7.1 × 106 CFU/ml, and at all pH except pH 1.5 at the lower inoculums of 5.4-7.1 × 103 CFU/ml or 5.4-7.1 × 101 CFU/ml. The organism remained metabolically viable at pH 1.5, 2.5, 3.5, and 4.5 and was able to recover and proliferate once placed in a neutral, nutrient-rich environment. CONCLUSION: In this study, EPEC demonstrated remarkable acid resistance and recovery at low pH without prior acid adaptation, which could prove to be problematic even in healthy people. In individuals with decreased gastric acidity, there is a higher probability of pathogen colonization and a resulting change in the gut microbiome. The results highlight the potential increase of food- and waterborne diseases in persons with compromised gastric function, or who are malnourished or immunocompromised. The data herein may possibly help in calculating more precisely the risk associated with consuming bacterial contaminated food and water in these individuals.


Asunto(s)
Adaptación Fisiológica/fisiología , Farmacorresistencia Bacteriana/fisiología , Escherichia coli Enteropatógena/efectos de los fármacos , Escherichia coli Enteropatógena/crecimiento & desarrollo , Escherichia coli Enteropatógena/fisiología , Ácido Gástrico , Viabilidad Microbiana/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Proliferación Celular/efectos de los fármacos , Recuento de Colonia Microbiana , Infecciones por Escherichia coli/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Estómago/microbiología , Estrés Fisiológico , Factores de Tiempo
6.
Artículo en Inglés | MEDLINE | ID: mdl-30636691

RESUMEN

OBJECTIVE: The International Liaison Committee on Resuscitation has found that there is a need for high-quality randomised trials of training interventions that improve the effectiveness of resuscitation skills. The objective of this study was to determine whether using a respiratory function monitor (RFM) during mask ventilation training with a manikin reduces facemask leak. DESIGN: Stratified, parallel-group, randomised controlled trial. Outcome assessors were blinded to group allocation. SETTING: Thirteen hospitals in Australia, including non-tertiary sites. PARTICIPANTS: Consecutive sample of healthcare professionals attending a structured newborn resuscitation training course. INTERVENTIONS: An RFM providing real-time, objective, leak, flow and volume information was attached to the facemask during 1.5 hours of newborn ventilation and simulation training using a manikin. Participants were randomised to have the RFM display visible (intervention) or masked (control), using a computer-generated randomisation sequence. MAIN OUTCOME MEASURES: The primary outcome was facemask leak measured after neonatal facemask ventilation training. Tidal volume was an important secondary outcome measure. RESULTS: Participants were recruited from May 2016 to November 2017. Of 402 eligible participants, two refused consent. Four hundred were randomised, 200 to each group, of whom 194 in each group underwent analysis. The median (IQR) facemask leak was 23% (8%-41%) in the RFM visible group compared with 35% (14%-67%) in the masked group, p<0.0001, difference (95% CI) in medians 12 (4 to 22). CONCLUSIONS: The display of information from an RFM improved the effectiveness of newborn facemask ventilation training. TRIAL REGISTRATION NUMBER: ACTRN12616000542493, pre-results.

7.
Magn Reson Med ; 81(1): 90-101, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29802643

RESUMEN

PURPOSE: In this study, a golden ratio stack of spiral (GRASS) sequence that used both golden step and golden angle ordering was implemented. The aim was to demonstrate that GRASS acquisitions could be flexibly reconstructed as both cardiac-gated and time-resolved angiograms. METHODS: Image quality of time-resolved and cardiac-gated reconstructions of the GRASS sequence were compared to 3 conventional stack of spirals (SoS) acquisitions in an in silico model. In 10 patients, the GRASS sequence was compared to conventional breath hold angiography (BH-MRA) in terms of image quality and for vessel measurement. Vessel measurements were also compared to cine images. RESULTS: In the cardiac-gated in silico model, the image quality of GRASS was superior to regular and golden-angle with regular step SoS approaches. In the time-resolved model, GRASS image quality was comparable to the golden-angle with regular step technique and superior to regular SoS acquisitions. In patients, there was no difference in qualitative image scores between GRASS and BH-MRA, but SNR was lower. There was good agreement in vessel measurements between the GRASS reconstructions and conventional MR techniques (BH-MRA: 29.8 ± 5.6 mm, time-resolved GRASS-MRA: 29.9 ± 5.4 mm, SSFP diastolic: 29.4 ± 5.8 mm, cardiac-gated GRASS-MRA diastolic: 29.5 ± 5.5 mm, P > 0.87). CONCLUSION: We have demonstrated that the GRASS acquisition enables flexible reconstruction of the same raw data as both time-resolved and cardiac-gated volumes. This may enable better interrogation of anatomy in congenital heart disease.

8.
Emerg Med J ; 36(4): 219-224, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30580317

RESUMEN

INTRODUCTION: Death due to opioid overdose was declared a public health crisis in Canada in 2015. Traditionally, patients who have overdosed on opioids that are managed by emergency medical services (EMS) are treated with the opioid antagonist naloxone, provided ventilatory support and subsequently transported to hospital. However, certain EMS agencies have permitted patients who have been reversed from opioid overdose to refuse transport, if the patient exhibits capacity to do so. Evidence on the safety of this practice is limited. Therefore, our intent was to examine the available literature to determine mortality and serious adverse events within 48 hours of EMS treat and release due to suspected rebound opioid toxicity after naloxone administration. METHODS: A systematic search was performed on 11 May 2017 in PubMed, Cochrane Central, Embase and CINHAL. Studies that reported on the outcome of patients treated with prehospital naloxone and released at the scene were included. Analyses for incidence of mortality and adverse events at the scene were conducted. Risk of bias and assessment of publication bias was also done. RESULTS: 1401 records were screened after duplicate removal. Eighteen full-text studies were reviewed with seven selected for inclusion. None were found to be high risk of bias. In most studies, heroin was the source of the overdose. Mortality within 48 hours was infrequent with only four deaths among 4912 patients ï´¾0.081%ï´¿ in the seven studies. Only one study reported on adverse events and found no incidence of adverse events from their sample of 71 released patients. CONCLUSION: Mortality or serious adverse events due to suspected rebound toxicity in patients released on scene post-EMS treatment with naloxone were rare. However, studies involving longer-acting opioids were rare and no study involved fentanyl.


Asunto(s)
Analgésicos Opioides/envenenamiento , Sobredosis de Droga/tratamiento farmacológico , Sobredosis de Droga/mortalidad , Servicios Médicos de Urgencia , Naloxona/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Humanos
9.
Arch Dis Child Fetal Neonatal Ed ; 104(5): F535-F539, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30567774

RESUMEN

OBJECTIVE: To compare the resistance of interfaces used for the delivery of nasal continuous positive airway pressure (CPAP) in neonates, as measured by the generated system pressure at fixed gas flows, in an in vitro setting. DESIGN: Gas flows of 6, 8 and 10 L/min were passed through three sizes of each of a selection of available neonatal nasal CPAP interfaces (Hudson prong, RAM Cannula, Fisher & Paykel prong, Infant Flow prong, Fisher & Paykel mask, Infant Flow mask). The expiratory limb was occluded and pressure differential measured using a calibrated pressure transducer. RESULTS: Variation in resistance, assessed by mean pressure differential, was seen between CPAP interfaces. Binasal prong interfaces typically had greater resistance at the smallest assessed sizes, and with higher gas flows. However, Infant Flow prongs produced low pressures (<1.5 cmH2O) at all sizes and gas flows. RAM Cannula had a high resistance, producing a pressure >4.5 cmH2O at all sizes and gas flows. Both nasal mask interfaces had low resistance at all assessed sizes and gas flows, with recorded pressure <1 cmH2O in all cases. CONCLUSIONS: There is considerable variation in measured resistance of available CPAP interfaces at gas flows commonly applied in clinical neonatal care. Use of interfaces with high resistance may result in a greater drop in delivered airway pressure in comparison to set circuit pressure, which may have implications for clinical efficacy. Device manufacturers and clinicians should consider CPAP interface resistance prior to introduction into routine clinical care.


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua/instrumentación , Cuidado Intensivo Neonatal/métodos , Ensayo de Materiales/métodos , Neonatología , Cánula , Diseño de Equipo , Humanos , Recién Nacido , Cuidado Intensivo Neonatal/normas , Neonatología/instrumentación , Neonatología/métodos , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Dispositivos de Protección Respiratoria
10.
Pediatrics ; 143(1)2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30578325

RESUMEN

: media-1vid110.1542/5839981898001PEDS-VA_2018-1825Video Abstract CONTEXT: The International Liaison Committee on Resuscitation prioritized to rigorously review the initial fraction of inspired oxygen (Fio2) during resuscitation of newborns. OBJECTIVE: This systematic review and meta-analysis provides the scientific summary of initial Fio2 in term and late preterm newborns (≥35 weeks' gestation) who receive respiratory support at birth. DATA SOURCES: Medline, Embase, Evidence Based Medicine Reviews, and Cumulative Index to Nursing and Allied Health Literature were searched between January 1, 1980 and August 10, 2018. STUDY SELECTION: Studies were selected by pairs of independent reviewers in 2 stages, with a Cohen's κ of 0.8 and 1.0. DATA EXTRACTION: Pairs of independent reviewers extracted data, appraised risk of bias, and assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence. RESULTS: Five randomized controlled trials (RCTs) and 5 quasi RCTs included 2164 patients. Room air (Fio2 0.21) was associated with a statistically significant benefit in short-term mortality compared with 100% oxygen (Fio2 1.0) (7 RCTs; n = 1469; risk ratio [RR] = 0.73; 95% confidence interval [CI]: 0.57 to 0.94). No significant differences were observed in neurodevelopmental impairment (2 RCTs; n = 360; RR = 1.41; 95% CI: 0.77 to 2.60) or hypoxic-ischemic encephalopathy (5 RCTs; n = 1315; RR = 0.89; 95% CI: 0.68 to 1.18). LIMITATIONS: The Grading of Recommendations Assessment, Development and Evaluation certainty of evidence was low for short-term mortality and hypoxic-ischemic encephalopathy and very low for neurodevelopmental impairment. CONCLUSIONS: Room air has a 27% relative reduction in short-term mortality compared with Fio2 1.0 for initiating neonatal resuscitation ≥35 weeks' gestation.

11.
Pediatrics ; 143(1)2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30578326

RESUMEN

: media-1vid110.1542/5839981895001PEDS-VA_2018-1828Video Abstract CONTEXT: The International Liaison Committee on Resuscitation prioritized to review the initial fraction of inspired oxygen (Fio2) during the resuscitation of preterm newborns. OBJECTIVES: This systematic review and meta-analysis provides the scientific summary of initial Fio2 in preterm newborns (<35 weeks' gestation) who receive respiratory support at birth. DATA SOURCES: Medline, Embase, Evidence-Based Medicine Reviews, and Cumulative Index to Nursing and Allied Health Literature were searched between January 1, 1980 and August 10, 2018. STUDY SELECTION: Studies were selected by pairs of independent reviewers in 2 stages with a Cohen's κ of 0.8 and 1.0. DATA EXTRACTION: Pairs of independent reviewers extracted data, appraised the risk of bias (RoB), and assessed Grading of Recommendations Assessment, Development and Evaluation certainty. RESULTS: Ten randomized controlled studies and 4 cohort studies included 5697 patients. There are no statistically significant benefits of or harms from starting with lower compared with higher Fio2 in short-term mortality (n = 968; risk ratio = 0.83 [95% confidence interval 0.50 to 1.37]), long-term mortality, neurodevelopmental impairment, or other key preterm morbidities. A sensitivity analysis in which 1 study with a high RoB was excluded failed to reveal a reduction in mortality with initial low Fio2 (n = 681; risk ratio = 0.63 [95% confidence interval 0.38 to 1.03]). LIMITATIONS: The Grading of Recommendations Assessment, Development and Evaluation certainty of evidence was very low for all outcomes due to RoB, inconsistency, and imprecision. CONCLUSIONS: The ideal initial Fio2 for preterm newborns is still unknown, although the majority of newborns ≤32 weeks' gestation will require oxygen supplementation.

12.
Int J Cancer ; 2018 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-30499236

RESUMEN

As a follow-up to genome-wide association analysis of common variants associated with ovarian carcinoma (cancer), this study considers seven well-known ovarian cancer risk factors and their interactions with 28 genome-wide significant common genetic variants. The interaction analyses were based on data from 9,971 ovarian cancer cases and 15,566 controls from 17 case-control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs never) and rs13255292 (P-value = 3.48 x 10-4 ). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI=0.46-0.60) compared to 0.71 (95%CI=0.66-0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1-5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene-environment analysis in ovarian cancer. This article is protected by copyright. All rights reserved.

13.
Oncotarget ; 9(78): 34735-34747, 2018 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-30410673

RESUMEN

TKI resistance remains a major impediment to successful treatment of CML. In this study, we investigated the emerging modes of ponatinib resistance in TKI-naïve and dasatinib resistant BCR-ABL1+ cell lines. To investigate potential resistance mechanisms, ponatinib resistance was generated in BCR-ABL1+ cell-lines by long-term exposure to increasing concentrations of ponatinib. Two cell lines with prior dasatinib resistance demonstrated BCR-ABL1 kinase domain (KD) mutation(s) upon exposure to ponatinib. In one of these cell lines the T315I mutation had emerged during dasatinib exposure. When further cultured with ponatinib, the T315I mutation level and BCR-ABL1 mRNA expression level were increased. In the other cell line, compound mutations G250E/E255K developed with ponatinib exposure. In contrast, the ponatinib resistant cell lines that had no prior exposure to other TKIs (TKI-naïve) did not develop BCR-ABL1 KD mutations. Rather, both of these cell lines demonstrated Bcr-Abl-independent resistance via Axl overexpression. Axl, a receptor tyrosine kinase, has previously been associated with imatinib and nilotinib resistance. Ponatinib sensitivity was restored following Axl inhibition or shRNA-mediated-knockdown of Axl, suggesting that Axl was the primary driver of resistance and a potential target for therapy in this setting.

14.
PLoS One ; 13(10): e0205487, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30335769

RESUMEN

BACKGROUND: It is unclear whether unintended pregnancies are associated with adverse outcomes. Data are predominantly from high-income countries and have methodological limitations, calling the findings into question. This research was designed to overcome these limitations and assess the relationships between pregnancy intention and miscarriage, stillbirth, low birthweight, neonatal death and postnatal depression in a low-income country. METHODS: The pregnancy intention of 4,244 pregnant women in Mchinji District, Malawi, was measured using the validated Chichewa version of the London Measure of Unplanned Pregnancy (LMUP). Women were re-interviewed postnatally to assess pregnancy outcome. Postnatal depression was assessed using the WHO's Self-Reporting Questionnaire. Multivariable regressions were conducted, with the choice of confounders informed by a pre-existing conceptual epidemiological hierarchy. RESULTS: Planned pregnancies are associated with a reduced risk of any (adjusted RR 0.90 [95%CI 0.86, 0.95]) or high symptoms of depression (adjusted RR 0.76 [95%CI 0.63, 0.91]) compared to unplanned pregnancies in rural Malawi. There was no relationship between pregnancy intention and the composite measure of miscarriage, stillbirth, low birthweight and neonatal death. There was some evidence that greater pregnancy intention was associated with reduced adjusted risk of stillbirth (0·93 [95%CI 0·87, 1·00]). CONCLUSION: Our study is the first to use a psychometrically valid measure of pregnancy intention, and to do so antenatally. As pregnancy intention increases, the risk of postnatal depression and, possibly, stillbirth decreases. This suggests a new, clinical use for the LMUP; identifying women antenatally who are at risk of these adverse pregnancy outcomes.

15.
J Pathol Clin Res ; 4(4): 250-261, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30062862

RESUMEN

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.

16.
Nat Commun ; 9(1): 3166, 2018 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-30093612

RESUMEN

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.

17.
Transl Lung Cancer Res ; 7(3): 272-280, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30050765

RESUMEN

Lung cancer is the leading cause of cancer-related death in the United States (U.S.) and is the second most common non-skin cancer among men and women, accounting for about 30% of cancer-related deaths. There is clear and accumulating evidence that continued tobacco use has multiple adverse effects on cancer treatment outcomes, including greater probability of recurrence, second primary malignancies, reduced survival, greater symptom burden, and poorer quality of life (QOL). Recent findings suggest an avenue to significantly mitigate the impact of smoking on lung cancer mortality rates through the use of low-dose computed tomography (LDCT) lung cancer screening. Based on the reviewed evidence (type B), the U.S. Preventive Services Task Force (USPSTF) guidelines of 2015 recommend screening combined with smoking cessation interventions for high-risk heavy smokers and recent quitters. These practice changes offer opportunities to develop novel smoking cessation strategies tailored to highly specific settings that aim to amplify the survivorship gains expected from screening alone. However, there is a paucity of research and data that speaks to the feasibility and efficacy of providing smoking cessation treatment specifically within the context of the LDCT lung cancer screening environment. While some studies have attempted to characterize the parameters within which smoking cessation interventions should be implemented in this context, further research is needed to explore relevant factors such as the format, components, and timing of interventions, as well as the influence of risk perceptions and results of the screening itself on motivation and ability to quit smoking.

18.
Diagnostics (Basel) ; 8(2)2018 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-29882765

RESUMEN

Biomarkers have the potential to aid in the study of Alzheimer’s disease (AD); unfortunately, AD biomarker values often have a high degree of overlap between healthy and AD individuals. This study investigates the potential utility of a series of novel AD biomarkers, the sixty second 129Xe retention time, and the xenon washout parameter, based on the washout of hyperpolarized 129Xe from the brain of AD participants following inhalation. The xenon washout parameter is influenced by cerebral perfusion, T1 relaxation of xenon, and the xenon partition coefficient, all factors influenced by AD. Participants with AD (n = 4) and healthy volunteers (n = 4) were imaged using hyperpolarized 129Xe magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to determine the amount of retained xenon in the brain. At 60 s after the breath hold, AD patients retained significantly higher amounts of 129Xe compared to healthy controls. Data was fit to a pharmacokinetic model and the xenon washout parameter was extracted. Xenon washout in white and grey matter occurs at a slower rate in Alzheimer’s participants (129Xe half-life time of 42 s and 43 s, respectively) relative to controls (20 s and 16 s, respectively). Following larger scale clinical trials for validation, the xenon washout parameter has the potential to become a useful biomarker for the support of AD diagnosis.

19.
Int J Occup Environ Med ; 9(2): 69-78, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29667644

RESUMEN

BACKGROUND: Emotional distress is becoming a great concern and is more common in both developed and developing countries. It is associated with several disease conditions. OBJECTIVE: To determine the prevalence of self-perceived emotional distress and its relation to work-related musculoskeletal disorders (WRMSDs) in nurses. METHODS: A self-administered questionnaire survey was carried out on 660 female nurses working in public hospitals in the Klang Valley, Malaysia. The validated Malay version of the standardized Nordic musculoskeletal questionnaire (M-SNMQ) was used to identify the annual prevalence of WRMSDs; perceived emotional distress was assessed using the validated Malay short version, depression, anxiety, and stress (M-DASS) instrument. In addition, socio-demographic and occupational profiles of the participants were considered. Factors associated with WRMSDs were identified using logistic regression analysis. RESULTS: A total of 376 nurses completed the survey (response rate 83.3%). 73.1% of the nursing staffs experienced WRMSDs in at least one anatomical site 12 months prior to the study. 75% of nurses expressed emotional distress. Of these, over half also reported anxiety and stress. Multiple logistic regression analysis showed that stress and anxiety significantly increased the risk of WRMSDs by approximately twofold. CONCLUSION: There were significant associations between emotional distress and WRMSDs. Future longitudinal studies are therefore needed to investigate and identify the sources of emotional distress (non-occupational and occupational) to be used to establish preventive strategies to reduce the risk of WRMSDs.


Asunto(s)
Enfermedades Musculoesqueléticas/psicología , Enfermeras y Enfermeros/psicología , Enfermedades Profesionales/psicología , Estrés Psicológico/psicología , Adulto , Femenino , Humanos , Malasia , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Profesionales/epidemiología , Prevalencia , Encuestas y Cuestionarios
20.
Br J Cancer ; 118(11): 1513-1517, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29670295

RESUMEN

BACKGROUND: Telomeres protect cells from genomic instability. We examined telomere length and lung cancer risk prospectively in heavy smokers. METHODS: In a nested case-control study with 709 cases and 1313 controls, conditional logistic regression was used to evaluate associations between telomere length (global, chromosome 5p, and 13q) and lung cancer risk by histotype, controlling for detailed smoking history. RESULTS: Risks of overall lung cancer and adenocarcinoma were suggestively elevated among individuals with telomere length in the longest tertile. No clear patterns were observed for other histotypes, or for chromosome 5p or 13q telomere length. Associations with adenocarcinoma were strongest among (OR, 95% CI for longest versus shortest tertile): former smokers (2.26, 1.03-4.96), individuals <65 years (2.22, 1.13-4.35), and women (2.21, 0.99-4.93). CONCLUSIONS: Our large study of heavy smokers adds additional evidence that long telomere length prior to diagnosis is associated with risk of lung adenocarcinoma, but not other histotypes.

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