Nonadherence to antihypertensive treatment is a critical contributor to suboptimal blood pressure control. There are limited and heterogeneous data on the risk factors for nonadherence because few ...studies used objective-direct diagnostic methods. We used high-performance liquid chromatography-tandem mass spectrometry of urine and serum to detect nonadherence and explored its association with the main demographic- and therapy-related factors in 1348 patients with hypertension from 2 European countries. The rates of nonadherence to antihypertensive treatment were 41.6% and 31.5% in the UK and Czech populations, respectively. Nonadherence was inversely related to age and male sex. Each increase in the number of antihypertensive medications led to 85% and 77% increase in nonadherence (
<0.001) in the UK and Czech populations, respectively. The odds of nonadherence to diuretics were the highest among 5 classes of antihypertensive medications (
≤0.005 in both populations). The predictive model for nonadherence, including age, sex, diuretics, and the number of prescribed antihypertensives, showed area under the curves of 0.758 and 0.710 in the UK and Czech populations, respectively. The area under the curves for the UK model tested on the Czech data and for the Czech model tested on UK data were calculated at 0.708 and 0.756, respectively. We demonstrate that the number and class of prescribed antihypertensives are modifiable risk factors for biochemically confirmed nonadherence to blood pressure-lowering therapy. Further development of discriminatory models incorporating these parameters might prove clinically useful in assessment of nonadherence in countries where biochemical analysis is unavailable.
Coronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated ...comprehensively, because available studies have involved limited genomic scope and limited sample sizes.
This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention.
Using a meta-analytic approach to combine large-scale, genome-wide, and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS) consisting of 1.7 million genetic variants. We externally tested metaGRS, both by itself and in combination with available data on conventional risk factors, in 22,242 CAD cases and 460,387 noncases from the UK Biobank.
The hazard ratio (HR) for CAD was 1.71 (95% confidence interval CI: 1.68 to 1.73) per SD increase in metaGRS, an association larger than any other externally tested genetic risk score previously published. The metaGRS stratified individuals into significantly different life course trajectories of CAD risk, with those in the top 20% of metaGRS distribution having an HR of 4.17 (95% CI: 3.97 to 4.38) compared with those in the bottom 20%. The corresponding HR was 2.83 (95% CI: 2.61 to 3.07) among individuals on lipid-lowering or antihypertensive medications. The metaGRS had a higher C-index (C = 0.623; 95% CI: 0.615 to 0.631) for incident CAD than any of 6 conventional factors (smoking, diabetes, hypertension, body mass index, self-reported high cholesterol, and family history). For men in the top 20% of metaGRS with >2 conventional factors, 10% cumulative risk of CAD was reached by 48 years of age.
The genomic score developed and evaluated here substantially advances the concept of using genomic information to stratify individuals with different trajectories of CAD risk and highlights the potential for genomic screening in early life to complement conventional risk prediction.
Adult height is associated with risk of several diseases, but the breadth of such associations and whether these associations are primary or due to confounding are unclear. We examined the ...association of adult height with 50 diseases spanning multiple body systems using both epidemiological and genetic approaches, the latter to identify un-confounded associations and possible underlying mechanisms.
We examined the associations for adult height (using logistic regression adjusted for potential confounders) and genetically determined height (using a two-sample Mendelian randomisation approach with height-associated genetic variants as instrumental variables) in 417,434 individuals of white ethnic background participating in the UK Biobank. We undertook pathway analysis of height-associated genes to identify biological processes that could link height and specific diseases.
Height was associated with 32 diseases and genetically determined height associated with 12 diseases. Of these, 11 diseases showed a concordant association in both analyses, with taller height associated with reduced risks of coronary artery disease (odds ratio per standard deviation (SD) increase in height OR
= 0.80, 95% CI 0.78-0.81; OR per SD increase in genetically determined height OR
= 0.86, 95% CI 0.82-0.90), hypertension (OR
= 0.83, 95% CI 0.82-0.84; OR
= 0.88, 95% CI 0.85-0.91), gastro-oesophageal reflux disease (OR
= 0.85, 95% CI 0.84-0.86; OR
= 0.94, 95% CI 0.92-0.97), diaphragmatic hernia (OR
= 0.81, 95% CI 0.79-0.82; OR
= 0.91, 95% CI 0.88-0.94), but increased risks of atrial fibrillation (OR
= 1.42, 95% CI 1.38-1.45; OR
= 1.33, 95% CI 1.26-1.40), venous thromboembolism (OR
= 1.18, 95% CI 1.16-1.21; OR
= 1.15, 95% CI 1.11-1.19), intervertebral disc disorder (OR
= 1.15, 95% CI 1.13-1.18; OR
= 1.14, 95% CI 1.09-1.20), hip fracture (OR
= 1.19, 95% CI 1.12-1.26; OR
= 1.27, 95% CI 1.17-1.39), vasculitis (OR
= 1.15, 95% CI 1.11-1.19; OR
= 1.20, 95% CI 1.14-1.28), cancer overall (OR
= 1.09, 95% CI 1.08-1.11; OR
= 1.06, 95% CI 1.04-1.08) and breast cancer (OR
= 1.08, 95% CI 1.06-1.10; OR
= 1.07, 95% CI 1.03-1.11). Pathway analysis showed multiple height-associated pathways associating with individual diseases.
Adult height is associated with risk of a range of diseases. We confirmed previously reported height associations for coronary artery disease, atrial fibrillation, venous thromboembolism, intervertebral disc disorder, hip fracture and cancer and identified potential novel associations for gastro-oesophageal reflux disease, diaphragmatic hernia and vasculitis. Multiple biological mechanisms affecting height may affect the risks of these diseases.
We hypothesized that screening for nonadherence to antihypertensive treatment using liquid chromatography-tandem mass spectrometry-based biochemical analysis of urine/serum has therapeutic ...applications in nonadherent hypertensive patients. A retrospective analysis of hypertensive patients attending specialist tertiary care centers was conducted in 2 European countries (United Kingdom and Czech Republic). Nonadherence to antihypertensive treatment was diagnosed using biochemical analysis of urine (United Kingdom) or serum (Czech Republic). These results were subsequently discussed with each patient, and data on follow-up clinic blood pressure (BP) measurements were collected from clinical files. Of 238 UK patients who underwent biochemical urine analysis, 73 were nonadherent to antihypertensive treatment. Their initial urinary adherence ratio (the ratio of detected to prescribed antihypertensive medications) increased from 0.33 (0-0.67) to 1 (0.67-1) between the first and the last clinic appointments. The observed increase in the urinary adherence ratio in initially nonadherent UK patients was associated with the improved BP control; by the last clinic appointment, systolic and diastolic BPs were ≈19.5 and 7.5 mm Hg lower than at baseline (
=0.001 and 0.009, respectively). These findings were further corroborated in 93 nonadherent hypertensive patients from Czech Republic-their average systolic and diastolic BPs dropped by ≈32.6 and 17.4 mm Hg, respectively (
<0.001), on appointments after the biochemical analysis. Our data show that nonadherent hypertensive patients respond to liquid chromatography-tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop. Such repeated biochemical analyses should be considered as a therapeutic approach in nonadherent hypertensive patients.
Abstract
We hypothesised that measuring changes in urinary levels of EV and miR will predict the onset of acute kidney injury in cardiac surgery patients. The study was performed in the cohort of the ...REVAKI-2 trial. Urine samples were collected before and 24 h after the procedure from 94 cardiac surgery patients. Urinary particle concentrations and size distribution were assessed using NanoSight. EV derivation and levels were measured using flow cytometry. Samples from 10 selected patients were sequenced, and verification was performed with advanced TaqMan assays in samples from all patients. Urinary particle concentrations significantly increased in patients with AKI after surgery, with the percentage of EV positive for CD105 and β1-integrin also increasing. Pre-surgery podocalyxin-positive EV were significantly lower in patients with AKI. Their levels correlated with the severity of the injury. Pre-operative miR-125a-5p was expressed at lower levels in urine from patients with AKI when adjusted for urinary creatinine. Levels of miR-10a-5p were lower after surgery in AKI patients and its levels correlated with the severity of the injury. Pre-operative levels of podocalyxin EVs, urinary particle concentrations and miR-125a-5p had moderate AKI predictive value and, in a logistic model together with ICU lactate levels, offered good (AUC = 82%) AKI prediction.
Neonatal Vitamin K prophylaxis is an effective intervention for reducing vitamin K deficiency bleeding. A recently published report of parental refusal of vitamin K prompted an investigation of the ...prevalence and characteristics of this group, and exploration of whether these same parents were likely to subsequently refuse immunization for their children.
We conducted a retrospective population-based cohort study of all infants born in Alberta between 2006 and 2012 by using linkage of administrative health data. Risk factors for vitamin K refusal were determined by using Poisson regression. The association between vitamin K refusal and nonimmunization was assessed using relative risk.
Among the 282378 children in the cohort, 99.7% received vitamin K and 0.3% declined. Midwife-assisted deliveries were more likely to be associated with vitamin K refusal compared with physician-attended delivery (risk ratio 8.4, 95% confidence interval CI 6.5-11.0). Planned home delivery (risk ratio 4.9, CI 3.8-6.4) or delivery in a birth center (risk ratio 3.6, CI 2.3-5.6) were more likely to result in decline of vitamin K compared with hospital delivery. Vitamin K refusal was associated with a 14.6 (CI 13.9-15.3) higher relative risk of having no recommended childhood vaccines at 15 months.
This is the first population-based study to characterize parents who are likely to decline vitamin K for their infants and whose children are likely to be unimmunized. These findings enable earlier identification of high-risk parents and provide an opportunity to enact strategies to increase uptake of vitamin K and childhood immunizations.
Background
We assessed the prevalence and pregnancy outcomes of pre‐existing diabetes mellitus (pre‐DM) and gestational diabetes mellitus (GDM) in Alberta, Canada, 2005–11.
Methods
327 198 singleton ...and 5552 twin pregnancies resulting in live births or stillbirths were included. The odds ratios of adverse outcomes were evaluated comparing pre‐DM with no diabetes and GDM with no diabetes, controlling for maternal characteristics.
Results
Diabetes complicated 6.3% of pregnancies, with 88% being GDM. In singleton pregnancies, pre‐DM and GDM were associated with increased risks of pre‐eclampsia (adjusted odds ratio aOR = 3.38 and 1.83, respectively), cesarean delivery (aOR 2.53, 1.55), spontaneous preterm (aOR 4.20, 1.71), and labor‐induced preterm (aOR 3.82, 2.00) in the mother, and macrosomia (aOR 2.11, 1.30), shoulder dystocia (aOR 1.54, 1.32), congenital anomalies (aOR 1.61, 1.20), and neonatal intensive care unit (NICU) admissions (aOR 3.81, 1.60) in the infants. In addition, pre‐DM was associated with an increased likelihood of stillbirth (aOR 3.73) and neonatal death (aOR 2.00) compared with non‐diabetic pregnancies. In twin pregnancies, pre‐DM was associated with increased risks of spontaneous (aOR 3.54) and labor‐induced (aOR 3.57) preterm births, large for gestational age (LGA) infants (aOR 3.73), congenital anomalies (aOR 3.05) and NICU admissions (aOR 2.91); GDM was associated with an increased risk of pre‐eclampsia (aOR 1.54), cesarean delivery (aOR 1.57), and LGA infants (aOR 1.63).
Conclusions
Pre‐existing diabetes confers higher risks than GDM. Diabetes is associated with adverse outcomes in singleton and twin pregnancies, and the increased risks are generally similar or less in twins, probably due to their higher “baseline” risks and closer clinical monitoring.
摘要
背景
我们评估了2005‐11年加拿大亚伯达省妊娠前存在的糖尿病(preexisting diabetes mellitus,pre‐DM)与妊娠糖尿病(GDM)的患病率以及妊娠结局。
方法
研究纳入了327198名单胎妊娠以及5552名双胎妊娠并且最终分娩活胎或者死胎的孕妇。将pre‐DM与非糖尿病孕妇相比,GDM与非糖尿病孕妇相比,评估了她们的不良结局优势比,并且按照母亲的特征进行了校正。
结果
妊娠合并糖尿病的比例为6.3%,合并GDM的比例为88%。在单胎妊娠中,pre‐DM以及GDM都与孕妇发生先兆子痫(校正后的优势比aOR分别为3.38、1.83)、剖宫产(aOR分别为2.53、1.55)、自发性早产(aOR分别为4.20、1.71)以及劳动诱发早产(aOR分别为3.82、2.00)的风险增加有关,并且都与婴儿出现巨大儿(aOR分别为2.11、1.30)、肩难产(aOR分别为1.54、1.32)、先天异常(aOR分别为1.61、1.20)以及入住新生儿重症监护治疗病房(aOR分别为3.81、1.60)的风险增加有关。另外,与非糖尿病孕妇相比较,pre‐DM还与死胎(aOR为3.73)以及新生儿死亡(aOR为2.00)的可能性增加有关。在双胎妊娠中,pre‐DM与自发性早产(aOR为3.54)、劳动诱发早产(aOR为3.57)、过期妊娠胎儿(aOR为3.73)、先天异常(aOR为3.05)以及入住新生儿重症监护治疗病房(aOR为2.91)的风险增加有关;GDM与先兆子痫(aOR为1.54)、剖宫产(aOR为1.57)以及过期妊娠胎儿(aOR为1.63)的风险增加有关。
结论
与GDM相比较,妊娠前存在糖尿病导致的风险更高。在单胎妊娠与双胎妊娠中,糖尿病与不良结局有关,并且与单胎妊娠相比,双胎妊娠增加的风险通常都相似或者更少,这可能与她们的“基线”风险更高并且临床监测更紧密有关。
Good project management outcomes include completing projects to an acceptable level of quality, within budget and on time. As construction accidents may cause project delays, safety management plays ...an important role in a project's timely completion. This study aims to undertake a comparative study of HR practices adopted for safety management on construction projects in the United States (US) and Singapore and to investigate the relationship between HR practices and construction safety management outcomes (severity and frequency of accidents). The research method included exploratory interviews and industry surveys of contractors in the US and Singapore by email and post. Data were collected using structured questionnaires. Compared to Singapore contractors, the results show that US contractors' project management practices place significantly more emphasis on highlighting organizational safety values to new workers and taking working experience into account during the selection process. On the other hand, Singapore contractors place more emphasis on providing appropriate rest areas for workers. Many HR practices are significantly correlated with safety management outcomes. These include: taking age into consideration during selection process and giving feedback to workers about their unsafe behaviour. It is recommended that project managers adopt relevant HR practices that lead to more effective safety management on construction projects.
►Taking age, height and build into account during selection. ►Giving feedback to workers on their unsafe behaviour. ►Allowing workers to participate in decision making relating to safety.
Patient blood management (PBM) interventions aim to improve clinical outcomes by reducing bleeding and transfusion. We assessed whether existing evidence supports the routine use of combinations of ...these interventions during and after major surgery.
Five systematic reviews and a National Institute of Health and Care Excellence health economic review of trials of common PBM interventions enrolling participants of any age undergoing surgery were updated. The last search was on June 1, 2019. Studies in trauma, burns, gastrointestinal haemorrhage, gynaecology, dentistry, or critical care were excluded. The co-primary outcomes were: risk of receiving red cell transfusion and 30-day or hospital all-cause mortality. Treatment effects were estimated using random-effects models and risk ratios (RR) with 95% confidence intervals (CIs). Heterogeneity assessments used I2. Network meta-analyses used a frequentist approach. The protocol was registered prospectively (PROSPERO CRD42018085730).
Searches identified 393 eligible randomised controlled trials enrolling 54 917 participants. PBM interventions resulted in a reduction in exposure to red cell transfusion (RR=0.60; 95% CI 0.57, 0.63; I2=77%), but had no statistically significant treatment effect on 30-day or hospital mortality (RR=0.93; 95% CI 0.81, 1.07; I2=0%). Treatment effects were consistent across multiple secondary outcomes, sub-groups and sensitivity analyses that considered clinical setting, type of intervention, and trial quality. Network meta-analysis did not demonstrate additive benefits from the use of multiple interventions. No trial demonstrated that PBM was cost-effective.
In randomised trials, PBM interventions do not have important clinical benefits beyond reducing bleeding and transfusion in people undergoing major surgery.
ObjectiveTo identify research priorities that address the needs of people affected by cardiac surgery and those who support and care for them.DesignJames Lind Alliance (JLA) process—two surveys and a ...consensus workshop guided by an independent JLA adviser.SettingThe UK with international participation.ParticipantsThree stakeholder groups—heart surgery patients, carers and healthcare professionals involved in care delivery.MethodsThe initial survey was set to collect potential research questions in cardiac surgery as identified by stakeholders. Submitted questions were summarised into indicative questions. The existing evidence was searched to verify that these indicative questions had not been answered. In the second survey, stakeholders then voted for their top 10 from the list of unanswered questions. The top voted questions were taken forward for final ranking in a workshop.ResultsIn the initial survey, 629 respondents (28% patients/carers, 62% healthcare professionals) submitted 1082 potential questions. Of these, 797 in-scope questions were summarised into 49 indicative questions and of which 45 had not been answered by existing research. In the second survey, 492 respondents (43% patients/carers, 49% healthcare professionals) cast their votes with the top 12 from each of the three stakeholder groups totalling 21 questions advancing to the final priority setting workshop. The workshop attended by 25 delegates (10 patients/carers and 15 healthcare professionals) agreed on the top 10 research questions including long-term outcomes (quality of life), and aspects from preoperative personalised care (prehabilitation, frailty, comorbidities), intraoperative management (minimally invasive techniques), to prevention and management of postoperative complications (organ injury, atrial fibrillation, infection).ConclusionsThis Priority Setting Partnership (PSP) identified the priorities and unmet needs of patients and clinicians in cardiac surgery. The next step is to disseminate and implement the PSP results to ensure that these priorities shape future research and improve clinical services.
PDF
