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1.
Int J Cancer ; 148(2): 307-319, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32851660

RESUMO

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10-8 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

2.
Front Neurol ; 11: 589628, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224099

RESUMO

Rationale: More than half of patients who receive thrombolysis for acute ischaemic stroke fail to recanalize. Elucidating biological factors which predict recanalization could identify therapeutic targets for increasing thrombolysis success. Hypothesis: We hypothesize that individual patient plasmin potential, as measured by in vitro response to recombinant tissue-type plasminogen activator (rt-PA), is a biomarker of rt-PA response, and that patients with greater plasmin response are more likely to recanalize early. Methods: This study will use historical samples from the Barcelona Stroke Thrombolysis Biobank, comprised of 350 pre-thrombolysis plasma samples from ischaemic stroke patients who received serial transcranial-Doppler (TCD) measurements before and after thrombolysis. The plasmin potential of each patient will be measured using the level of plasmin-antiplasmin complex (PAP) generated after in-vitro addition of rt-PA. Levels of antiplasmin, plasminogen, t-PA activity, and PAI-1 activity will also be determined. Association between plasmin potential variables and time to recanalization [assessed on serial TCD using the thrombolysis in brain ischemia (TIBI) score] will be assessed using Cox proportional hazards models, adjusted for potential confounders. Outcomes: The primary outcome will be time to recanalization detected by TCD (defined as TIBI ≥4). Secondary outcomes will be recanalization within 6-h and recanalization and/or haemorrhagic transformation at 24-h. This analysis will utilize an expanded cohort including ~120 patients from the Targeting Optimal Thrombolysis Outcomes (TOTO) study. Discussion: If association between proteolytic response to rt-PA and recanalization is confirmed, future clinical treatment may customize thrombolytic therapy to maximize outcomes and minimize adverse effects for individual patients.

3.
BMC Cardiovasc Disord ; 20(1): 491, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225900

RESUMO

BACKGROUND: Clinic blood pressure measurement (CBPM) is currently the most commonly used form of screening for hypertension, however it might have a problem detecting white coat hypertension (WCHT) and masked hypertension (MHT). Home blood pressure measurement (HBPM) may be an alternative, but its diagnostic performance is inconclusive relative to CBPM. Therefore, this systematic review aimed to estimate the performance of CBPM and HBPM compared with ambulatory blood pressure measurement(ABPM) and to pool prevalence of WCHT and MHT. METHODS: Medline, Scopus, Cochrane Central Register of Controlled Trials and WHO's International Clinical Trials Registry Platform databases were searched up to 23rd January 2020. Studies having diagnostic tests as CBPM or HBPM with reference standard as ABPM, reporting sensitivity and specificity of both tests and/or proportion of WCHT or MHT were eligible. Diagnostic performance of CBPM and HBPM were pooled using bivariate mixed-effect regression model. Random effect model was applied to pool prevalence of WCHT and MHT. RESULTS: Fifty-eight studies were eligible. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of CBPM, when using 24-h ABPM as the reference standard, were 74% (95% CI: 65-82%), 79% (95% CI: 69%, 87%), and 11.11 (95% CI: 6.82, 14.20), respectively. Pooled prevalence of WCHT and MHT were 0.24 (95% CI 0.19, 0.29) and 0.29 (95% CI 0.20, 0.38). Pooled sensitivity, specificity, and DOR of HBPM were 71% (95% CI 61%, 80%), 82% (95% CI 77%, 87%), and 11.60 (95% CI 8.98, 15.13), respectively. CONCLUSIONS: Diagnostic performances of HBPM were slightly higher than CBPM. However, the prevalence of MHT was high in negative CBPM and some persons with normal HBPM had elevated BP from 24-h ABPM. Therefore, ABPM is still necessary for confirming the diagnosis of HT.

4.
Implement Sci ; 15(1): 98, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148294

RESUMO

BACKGROUND: Despite being one of the few evidence-based treatments for acute ischemic stroke, intravenous thrombolysis has low implementation rates-mainly due to a narrow therapeutic window and the health system changes required to deliver it within the recommended time. This systematic review and meta-analyses explores the differential effectiveness of intervention strategies aimed at improving the rates of intravenous thrombolysis based on the number and type of behaviour change wheel functions employed. METHOD: The following databases were searched: MEDLINE, EMBASE, PsycINFO, CINAHL and SCOPUS. Multiple authors independently completed study selection and extraction of data. The review included studies that investigated the effects of intervention strategies aimed at improving the rates of intravenous thrombolysis and/or onset-to-needle, onset-to-door and door-to-needle time for thrombolysis in patients with acute ischemic stroke. Interventions were coded according to the behaviour change wheel nomenclature. Study quality was assessed using the QualSyst scoring system for quantitative research methodologies. Random effects meta-analyses were used to examine effectiveness of interventions based on the behaviour change wheel model in improving rates of thrombolysis, while meta-regression was used to examine the association between the number of behaviour change wheel intervention strategies and intervention effectiveness. RESULTS: Results from 77 studies were included. Five behaviour change wheel interventions, 'Education', 'Persuasion', 'Training', 'Environmental restructuring' and 'Enablement', were found to be employed among the included studies. Effects were similar across all intervention approaches regardless of type or number of behaviour change wheel-based strategies employed. High heterogeneity (I2 > 75%) was observed for all the pooled analyses. Publication bias was also identified. CONCLUSION: There was no evidence for preferring one type of behaviour change intervention strategy, nor for including multiple strategies in improving thrombolysis rates. However, the study results should be interpreted with caution, as they display high heterogeneity and publication bias.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33144283

RESUMO

BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. METHODS: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e. inverse-variance meta-analysis, co-localization, and M-values), and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. RESULTS: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10-9). In addition, four novel sub-genome wide regions at 7p22.2, 7q22.1, 9p12 and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines, and expression quantitative trait loci (eQTL) data highlighted candidate target genes for further investigation. CONCLUSION: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.

6.
Australas J Ageing ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33166034

RESUMO

OBJECTIVE: To evaluate whether a safe medication strategy compared with usual care, provided to people with dementia during an unplanned admission, reduces readmissions to hospital and re-presentation to emergency departments within three months. METHODS: A prospective, controlled pre-/post-trial conducted at two regional hospitals in New South Wales, Australia. RESULTS: No treatment effect was seen for time to first re-presentation or readmission within three months (P = .3). Compliance with six strategies applicable for all participants in the intervention phase was 58%. There was no treatment effect for secondary outcomes including dose administration aid use, home medicines review (HMR) requests by general practitioners and completed HMRs; however, they were significantly higher at the intervention site in both phases. CONCLUSION: A bundle of care to improve medication safety in people with dementia did not reduce re-presentations or readmissions within three months.

7.
BMC Health Serv Res ; 20(1): 1082, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238996

RESUMO

BACKGROUND: Aboriginal and Torres Strait Islander people have high rates of avoidable hospital admissions for chronic conditions, however little is known about the frequency of avoidable admissions for this population. This study examined trends in avoidable admissions among Aboriginal and non-Aboriginal people with chronic conditions in New South Wales (NSW), Australia. METHODS: A historical cohort analysis using de-identified linked administrative data of Aboriginal patients and an equal number of randomly sampled non-Aboriginal patients between 2005/06 to 2013/14. Eligible patients were admitted to a NSW public hospital and who had one or more of the following ambulatory care sensitive chronic conditions as a principal diagnosis: diabetic complications, asthma, angina, hypertension, congestive heart failure and/or chronic obstructive pulmonary disease. The primary outcomes were the number of avoidable admissions for an individual in each financial year, and whether an individual had three or more admissions compared with one to two avoidable admissions in each financial year. Poisson and logistic regression models and a test for differences in yearly trends were used to assess the frequency of avoidable admissions over time, adjusting for sociodemographic variables and restricted to those aged ≤75 years. RESULTS: Once eligibility criteria had been applied, there were 27,467 avoidable admissions corresponding to 19,025 patients between 2005/06 to 2013/14 (71.2% Aboriginal; 28.8% non-Aboriginal). Aboriginal patients were 15% more likely than non-Aboriginal patients to have a higher number of avoidable admissions per financial year (IRR = 1.15; 95% CI: 1.11, 1.20). Aboriginal patients were almost twice as likely as non-Aboriginal patients to experience three or more avoidable admissions per financial year (OR = 1.90; 95% CI = 1.60, 2.26). There were no significant differences between Aboriginal and non-Aboriginal people in yearly trends for either the number of avoidable admissions, or whether or not an individual experienced three or more avoidable admissions per financial year (p = 0.859; 0.860 respectively). CONCLUSION: Aboriginal people were significantly more likely to experience frequent avoidable admissions over a nine-year period compared to non-Aboriginal people. These high rates reflect the need for further research into which interventions are able to successfully reduce avoidable admissions among Aboriginal people, and the importance of culturally appropriate community health care.

8.
J Am Geriatr Soc ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33124692

RESUMO

BACKGROUND/OBJECTIVES: Older people living in residential aged care facilities (RACFs) experience acute deterioration requiring assessment and decision making. We evaluated the impact of a large-scale regional Aged Care Emergency (ACE) program in reducing hospital admissions and emergency department (ED) transfers. DESIGN: A stepped wedge nonrandomized cluster trial with 11 steps, implemented from May 2013 to August 2016. SETTING: A large regional and rural area of northern and western New South Wales, Australia. PARTICIPANTS: Nine hospital EDs and 81 RACFs participated in the evaluation. INTERVENTION: The ACE program is an integrated nurse-led intervention underpinned by a community of practice designed to improve the capability of RACFs managing acutely unwell residents. It includes telephone support, evidence-based algorithms, defining goals of care for ED transfer, case management in the ED, and an education program. MEASUREMENTS: ED transfers and subsequent hospital admissions were collected from administrative data including 13 months baseline and 9 months follow-up. RESULTS: A total of 18,837 eligible ED visits were analyzed. After accounting for clustering by RACFs and adjusting for time of the year as well as RACF characteristics, a statistically significant reduction in hospital admissions (adjusted incident rate ratio = .79; 95% confidence interval [CI] = .68-.92); P = .0025) was seen (i.e., residents were 21% less likely to be admitted to the hospital). This was also observed in ED visit rates (adjusted incidence rate ratio = .80; 95% CI = .69-.92; P = .0023) (i.e., residents were 20% less likely to be transferred to the ED). Seven-day ED re-presentation fell from 5.7% to 4.9%, and 30-day hospital readmissions fell from 12% to 10%. CONCLUSION: The stepped wedge design allowed rigorous evaluation of a real-world large-scale intervention. These results confirm that the ACE program can be scaled up to a large geographic area and can reduce ED visits and hospitalization of older people with complex healthcare needs living in RACFs.

9.
BMC Med Genet ; 21(1): 210, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087043

RESUMO

BACKGROUND: Replication studies showed conflicting effects of ABCG2 and SLC2A9 polymorphisms on gout and serum urate. This meta-analysis therefore aimed to pool their effects across studies. METHODS: Studies were located from MEDLINE and Scopus from inception to 17th June 2018. Observational studies in adults with any polymorphism in ABCG2 or SLC2A9, and outcome including gout, hyperuricemia, and serum urate were included for pooling. Data extractions were performed by two independent reviewers. Genotype effects were pooled stratified by ethnicity using a mixed-effect logistic model and a multivariate meta-analysis for dichotomous and continuous outcomes. RESULTS: Fifty-two studies were included in the analysis. For ABCG2 polymorphisms, mainly studied in Asians, carrying 1-2 minor-allele-genotypes of rs2231142 and rs72552713 were respectively about 2.1-4.5 and 2.5-3.9 times higher odds of gout than non-minor-allele-genotypes. The two rs2231142-risk-genotypes also had higher serum urate about 11-18 µmol/l. Conversely, carrying 1-2 minor alleles of rs2231137 was about 36-57% significantly lower odds of gout. For SLC2A9 polymorphisms, mainly studied in Caucasians, carrying 1-2 minor alleles of rs1014290, rs6449213, rs6855911, and rs7442295 were about 25-43%, 31-62%, 33-64%, and 35-65% significantly lower odds of gout than non-minor-allele-genotypes. In addition, 1-2 minor-allele-genotypes of the latter three polymorphisms had significantly lower serum urate about 20-49, 21-51, and 18-54 µmol/l than non-minor-allele-genotypes. CONCLUSIONS: Our findings should be useful in identifying patients at risk for gout and high serum urate and these polymorphisms may be useful in personalized risk scores. TRIAL REGISTRATION: PROSPERO registration number: CRD42018105275 .

10.
Artigo em Inglês | MEDLINE | ID: mdl-33039640

RESUMO

BACKGROUND: Nonadherence is common among pregnant women prescribed inhaled corticosteroids (ICS) for asthma and may have serious consequences for mother and baby. Factors associated with ICS nonadherence have not been determined in this population. OBJECTIVES: To determine factors associated with {1} nonadherence to ICS in early-mid pregnancy (cross-sectional) and {2} persistent nonadherence to ICS during pregnancy (longitudinal). METHODS: Data used come from 3 prospective studies (2004-2019) involving women with asthma recruited by 23 weeks' gestation (N = 1614). Demographics, asthma history, and current symptoms were assessed, and spirometry was performed at baseline and throughout pregnancy. Women self-reported current medication use and number of ICS doses missed in the past week. Nonadherence was defined as ≥20% of prescribed dosages missed in the past week (baseline) and on at least 2 occasions during follow-up (persistent). Factors associated with ICS nonadherence were examined using backward stepwise logistic regression. RESULTS: Of 610 (38%) women prescribed ICS at baseline, 236 (39%) were classified as nonadherent. Of 612 (38%) women prescribed ICS during at least 2 follow-up visits, 149 (24%) were classified as persistent nonadherent. Factors associated with nonadherence at baseline were current or ex-smoking, non-Caucasian/non-Indigenous ethnicity, adult diagnosis of asthma, and lower lung function. Factors associated with persistent nonadherence to ICS were lower maternal age, higher parity, and no prescribed ICS at baseline. CONCLUSION: Young multiparous non-Caucasian/non-Indigenous mothers are at increased risk of being nonadherent to ICS during pregnancy. Strategies to improve ICS nonadherence should address maternal smoking and target women who (re-)initiate ICS use in pregnancy.

11.
Intern Med J ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016526

RESUMO

The diagnosis of polyneuropathy usually requires neurophysiological investigation, necessitating specialised testing and interpretation thereby increasing the time to final diagnosis. We investigated the predictive value of the clinical examination in patients with potential neuropathies. Patients were recruited based on their referral requesting neurophysiological testing. Two examiners tested ankle jerk reflexes and gradient to temperature sensation prior to the patient undergoing neurophysiology investigations, blinded to subsequent testing results. The neurophysiology investigations were either standard nerve conduction study (NCS) or thermal threshold testing (TTT) or both. These data were then analysed to determine the Kappa between examiners as well as sensitivity, specificity, and positive and negative likelihood ratios. There was a modest level of agreement between examiners for ankle jerk testing (Kappa=0.6) but poor agreement for gradient temperature testing (Kappa=0.3). Bilateral absence of ankle jerk reflexes was moderately associated with abnormal NCS, with the following characteristics: sensitivity 72%, specificity 91%, positive likelihood ratio 7.6, and negative likelihood ratio 0.3. The presence of a temperature gradient was poorly diagnostic for abnormal TTT: sensitivity 87%, specificity 14%, with positive and negative likelihood ratios close to 1. In conclusion, the absence of ankle jerks performed moderately well in identifying patients likely to have large fibre neuropathy and could potentially be used to help decide who should be sent for NCS. Gradient temperature testing was much more subjective and did not change the likelihood of abnormal TTT. This article is protected by copyright. All rights reserved.

12.
BMC Cardiovasc Disord ; 20(1): 432, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023494

RESUMO

BACKGROUND: Multiple studies have attempted to increase the rate of intravenous thrombolysis for ischemic stroke using interventions to promote adherence to guidelines. Still, many of them did not measure individual-level impact. This study aimed to make a posthoc comparison of the clinical outcomes of patients in the "Thrombolysis ImPlementation in Stroke (TIPS)" study, which aimed to improve rates of intravenous thrombolysis in Australia. METHODS: A posthoc analysis was conducted using individual-level patient data. Excellent (Three-month post treatment modified Rankin Score 0-2) and poor clinical outcome (Three-month post treatment modified Rankin Score 5-6) and post treatment parenchymal haematoma were the three main outcomes, and a mixed logistic regression model was used to assess the difference between the intervention and control groups. RESULTS: There was a non-significant higher odds of having an excellent clinical outcome of 57% (odds ratio: 1.57; 95% CI: 0.73-3.39) and 33% (odds ratio: 1.33; 95% CI: 0.73-2.44) during the active-and post-intervention period respectively, for the intervention compared to the control group. A non-significant lower odds of having a poor clinical outcome was also found in the intervention, relative to control group of 4% (odds ratio: 0.96; 95% CI: 0.56-2.07) and higher odds of having poor outcome of 44% (odds ratio: 1.44 95% CI: 0.61-3.41) during both active and post-intervention period respectively. Similarly, a non-significant lower odds of parenchymal haematoma was also found for the intervention group during the both active- (odds ratio: 0.53; 95% CI: 0.21-1.32) and post-intervention period (odds ratio: 0.96; 95% CI: 0.36-2.52). CONCLUSION: The TIPS multi-component implementation approach was not effective in reducing the odds of post-treatment severe disability at 90 days, or post-thrombolysis hemorrhage. TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.anzctr.org.au/ Unique Identifier: ACTRN12613000939796 .

13.
Obes Rev ; 21(12): e13127, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32869512

RESUMO

This review examined the risk of cardiovascular disease in adults with metabolically healthy overweight/obesity. A systematic review and meta-analysis using data from Medline, EMBASE, SCOPUS and Cochrane Library searched from inception up to 31st October 2019. We included prospective cohort studies of adults who are metabolically healthy or unhealthy. Outcomes were fatal and nonfatal cardiovascular events, all-cause mortality. Pooled relative risk was calculated for each outcome in populations with metabolically healthy overweight and metabolically healthy obesity using metabolically healthy normal weight as reference. A random-effects model was used for meta-analysis, and risk of bias assessment tool for nonrandomized studies assessed risk of bias within each study. Twenty-three prospective cohort studies with 4,492,723 participants were included. Cardiovascular disease risk was increased in metabolically healthy groups with overweight (RR = 1.34, CI: 1.23-1.46, n = 20, I2 = 90.3%) and obesity (RR = 1.58, CI: 1.34-1.85, n = 21, I2 = 92.2) compared with a reference group with metabolically healthy normal weight. Cardiovascular disease risk was similar irrespective of the number of risk factors used to define metabolically healthy and the risk remained in the group with no metabolic risk factors. Cardiovascular disease risk is increased in populations with overweight and obesity classified as metabolically healthy even when there were no metabolic risk factors.

14.
Mult Scler Relat Disord ; 46: 102524, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32971498

RESUMO

BACKGROUND: Multiple sclerosis (MS) is associated with a breakdown in the intracranial pulse wave dampening or windkessel effect. This is manifest by an increase in the arterial stroke volume and a decrease in the dampening afforded by both the CSF displaced into the spinal canal and the blood displaced by the venous sinus pulsation. There is evidence that the reduction in compliance of the sagittal and straight sinuses in MS is caused by an increase in venous pressure despite the jugular bulb pressures being normal. This implies MS patients have a venous outflow stenosis somewhere between the torcular and jugular bulbs. The purpose of the current study is to define the site, significance and cause of these stenoses. METHODS: 50 patients with MS were prospectively recruited from an MS clinic and compared to 50 matched control patients. Using 3DT1 post contrast images, a survey of the venous sinuses was performed looking for the narrowest portion of the sinuses in each of 4 segments from the sagittal sinus to jugular bulbs. The cross sectional areas and wetted circumferences of the venous sinuses were measured at each site to calculate the minimum hydraulic and effective diameters. The BMI, optic nerve sheath diameters and pituitary heights were measured. Statistical analysis was performed using non-parametric methods and was assessed using α≤0.05. RESULTS: Compared to controls, the MS patients' sagittal sinuses were 24% larger in cross-section (p=0.0001) with an 18% larger wetted circumference (p=0.0001). The MS patients' transverse sinuses had an average effective stenosis of 38% by area (p<0.0001) with 8/50 patients having a high grade stenosis of >65% by area and 16/50 a low grade stenosis of between 40-65% by area compared to 1/50 low grade stenoses in this segment in the controls. The commonest cause of the stenosis was a giant arachnoid granulation. The optic nerve sheaths were larger in MS than controls (p=0.0006). Comparing MS patients with transverse sinus stenosis to those without, the pituitary height was 16% smaller and BMI 25% larger (p=0.02 and 0.003 respectively) CONCLUSION: In patients with MS, the reduction in venous sinus compliance is associated with venous outflow stenoses in the transverse sinuses which increases the upstream venous pressure and dilates the sagittal sinuses. This finding suggests a continuum exists between MS and idiopathic intracranial hypertension.

15.
Biomolecules ; 10(9)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957504

RESUMO

The tyrosine kinase receptor A (NTRK1/TrkA) is increasingly regarded as a therapeutic target in oncology. In breast cancer, TrkA contributes to metastasis but the clinicopathological significance remains unclear. In this study, TrkA expression was assessed via immunohistochemistry of 158 invasive ductal carcinomas (IDC), 158 invasive lobular carcinomas (ILC) and 50 ductal carcinomas in situ (DCIS). TrkA was expressed in cancer epithelial and myoepithelial cells, with higher levels of TrkA positively associated with IDC (39% of cases) (p < 0.0001). Interestingly, TrkA was significantly increased in tumours expressing the human epidermal growth factor receptor-2 (HER2), with expression in 49% of HER2-positive compared to 25% of HER2-negative tumours (p = 0.0027). A panel of breast cancer cells were used to confirm TrkA protein expression, demonstrating higher levels of TrkA (total and phosphorylated) in HER2-positive cell lines. Functional investigations using four different HER2-positive breast cancer cell lines indicated that the Trk tyrosine kinase inhibitor GNF-5837 reduced cell viability, through decreased phospho-TrkA (Tyr490) and downstream AKT (Ser473) activation, but did not display synergy with Herceptin. Overall, these data highlight a relationship between the tyrosine kinase receptors TrkA and HER2 and suggest the potential of TrkA as a novel or adjunct target for HER2-positive breast tumours.

16.
Int J Surg ; 83: 144-151, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32927135

RESUMO

BACKGROUND: Mesh can be used to prevent incisional hernia (IH) occurrence. However, the effect of various mesh positions has never been compared. This study aimed to compare and rank the effect and safety of various mesh-augmented fascia closure techniques on hernia prophylaxis in midline laparotomy. METHODS: MEDLINE and SCOPUS were searched from inception to December 2019. Randomized clinical trials (RCTs) were eligible if they met the following criteria: comparison of any of the following interventions: onlay (OM), retrorectus (RM), preperitoneal (PM), intraperitoneal mesh (IM) augmentation, and primary suture closure (PSC); and reporting on any of these outcomes: IH, wound infection, seroma, hematoma, and dehiscence. Two independent reviewers extracted data and assessed the risk of bias. A two-stage random-effect network meta-analysis was performed, then intervention effects were pooled and ranked accordingly. RESULTS: A total of 20 RCTs were eligible. Only OM and RM showed a significantly lower risk of IH than PSC with pooled risk ratios (RRs), 95% confidence intervals (95%CI) of 0.24 (0.12, 0.46) and 0.32 (0.16, 0.66), and number needed to treat (NNTs) of 4 and 5, respectively. However, OM showed a significantly higher risk of seroma than PSC (RR 2.21 (1.44, 3.39) with a number needed to harm (NNH) of 14). Most mesh placements showed a higher risk of wound infection, except for RM, but none of these was significantly different. All mesh techniques, except RM, showed a reduction in dehiscence, but again these were not significantly different. CONCLUSIONS: OM and RM provided the most effective IH prevention relative to PSC. However, OM had a higher rate of seroma than RM and PSC. Other complications, including wound infection, hematoma, and dehiscence, were not significantly observed among these fascia closure techniques.

17.
Eat Behav ; 39: 101430, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32942238

RESUMO

AIM: To identify and describe the demographic and social-cognitive factors associated with excessive gestational weight gain using the Weight-Related Behaviours Questionnaire, within an Australian pregnancy cohort. BACKGROUND: Supporting women to achieve optimal weight gain in pregnancy is complex. Social-cognitive factors are recognised antecedents to, and mediators of, weight related behaviour change. Less is known about their role during pregnancy. METHODS: 159 women enrolled in a pregnancy cohort study completed the Weight-Related Behaviours Questionnaire (WRBQ) at approximately 19 weeks gestation, and total gestational weight gain was later measured at 36 weeks. Summary scores were reported descriptively. Multivariable logistic regression was used to test demographic (maternal age, pre pregnancy body mass index, parity, smoking status, marital status, education) and social-cognitive factors (weight locus of control, self- efficacy, attitudes towards weight gain, body image, feelings about motherhood, career orientation) as predictors of excessive gestational weight gain. FINDINGS: Maternal age was the sole demographic factor predictive of excessive gestational weight gain. Older participants (34-41 yrs) were less likely to gain excessive weight when compare to younger participants (18-24 yrs): Odds Ratio 0.20, 95% Confidence Interval 0.05, 0.82. Body image (measured as personal satisfaction and perception of own weight) was the sole social-cognitive factor associated with excessive gestational weight gain. For every one unit improvement in body image score, there was a 33% decreased odds of excessive gestational weight gain (OR 0.67, 95% CI 0.53, 0.85). CONCLUSION: This study suggests that younger maternal age and lower perceived body image are predictive of excessive gestational weight gain.

18.
Healthcare (Basel) ; 8(3)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32751986

RESUMO

This study reports carer strain and coping with medications for people with dementia with an unplanned admission to hospital, and it evaluates the impact of a safe medication intervention on carer coping and carer strain. This was a quasi-experimental pre/post-controlled trial that included a survey of carers about managing medications for people with dementia after discharge. For 88 carers who completed surveys, 33% were concerned about managing medications, and 40% reported difficulties with medication management, including resistive behaviours by people with dementia. Dose administration aids were used by 72% of carers; however, only 15% reported receiving a recent home medicines review by a community pharmacist. High carer strain was reported by 74% of carers. Carer comments described many issues that contributed to high carer stress, as well as their engagement in vigilant activities to maintain medication safety. Strategies that can contribute to carers managing medications and reducing their strain include an increased use of dose administration aids, increased provision of home medicines reviews, and increased education of health professionals to provide adequate support and education about managing medications.

19.
Health Educ Res ; 35(4): 243-257, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32632449

RESUMO

While there is some guidance to support the adaptation of evidence-based public health interventions, little is known about adaptation in practice and how to best support public health practitioners in its operationalization. This qualitative study was undertaken with researchers, methodologists, policy makers and practitioners representing public health expert organizations and universities internationally to explore their views on available adaptation frameworks, elicit potential improvements to such guidance, and identify opportunities to improve implementation of public health initiatives. Participants attended a face to face workshop in Newcastle, Australia in October 2018 where World Café and focus group discussions using Appreciative Inquiry were undertaken. A number of limitations with current guidance were reported, including a lack of detail on 'how' to adapt, limited information on adaptation of implementation strategies and a number of structural issues related to the wording and ordering of elements within frameworks. A number of opportunities to advance the field was identified. Finally, a list of overarching principles that could be applied together with existing frameworks was generated and suggested to provide a practical way of supporting adaptation decisions in practice.

20.
J Clin Med ; 9(7)2020 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-32664649

RESUMO

Abstract: Timely surgical intervention in hip fracture has been linked to improved outcomes. Direct Oral Anticoagulants (DOACs) are an emerging class of anticoagulants without evidence-based guidelines on surgical timing. This study aims to investigate how DOACs affect surgical timing and hence perioperative outcomes. A retrospective database/registry review was conducted for geriatric hip fracture patients aged 65 and over between 2011 and 2018. Primary outcome was 30-day mortality. Secondary outcomes included serious adverse events (SAE), transfusion and postoperative day (POD) 1 haemoglobin (Hb) levels. From a cohort of 3264 patients, 112 admitted subjects were taking DOACs; the annual proportion on DOACs increased over time. Mean time to surgery from last dose (Ts) was 2.2 (±1.0 SD) days. The primary outcome, 30-day mortality, occurred in 16 (14%) patients with secondary outcomes of SAEs in 25 (22%) patients and transfusion in 30 (27%) patients. Ts (days) did not significantly affect 30-day mortality (odds ratio (OR): 1.37, 95% confidence interval (CI): 0.80-2.33; p = 0.248), SAE (hazard ratio (HR): 1.03, 95% CI: 0.70-1.52; p = 0.885), transfusion (OR: 0.72 95% CI: 0.45 to 1.16; p = 0.177) or POD 1 Hb (OR: 1.99, 95% CI: -0.59 to 4.57; p = 0.129). Timing of surgery does not influence common surgical outcomes such as 30-day mortality, SAE, transfusion, and POD1 Hb in patients taking DOACs on admission.

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