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Observational studies have found associations between smoking and both poorer cognitive ability and lower educational attainment; however, evaluating causality is challenging. We used two complementary methods to explore this.
We conducted observational analyses of up to 12 004 participants in a cohort study (Study One) and Mendelian randomisation (MR) analyses using summary and cohort data (Study Two). Outcome measures were cognitive ability at age 15 and educational attainment at age 16 (Study One), and educational attainment and fluid intelligence (Study Two).
Study One: heaviness of smoking at age 15 was associated with lower cognitive ability at age 15 and lower educational attainment at age 16. Adjustment for potential confounders partially attenuated findings (e.g. fully adjusted cognitive ability β −0.736, 95% CI −1.238 to −0.233, p = 0.004; fully adjusted educational attainment β −1.254, 95% CI −1.597 to −0.911, p < 0.001). Study Two: MR indicated that both smoking initiation and lifetime smoking predict lower educational attainment (e.g. smoking initiation to educational attainment inverse-variance weighted MR β −0.197, 95% CI −0.223 to −0.171, p = 1.78 × 10−49). Educational attainment results were robust to sensitivity analyses, while analyses of general cognitive ability were less so.
We find some evidence of a causal effect of smoking on lower educational attainment, but not cognitive ability. Triangulation of evidence across observational and MR methods is a strength, but the genetic variants associated with smoking initiation may be pleiotropic, suggesting caution in interpreting these results. The nature of this pleiotropy warrants further study.
At International Harvester, a 1902 merger, the defining feature was discord. A J. P. Morgan financier by the name of George W. Perkins and a formal agreement initiated changes to mitigate stress and struggle. Existing research dates improvement to 1906. This paper extends the analysis and documents that, among changes, entrepreneur William Deering and his children parted with some holdings, helping to diminish tensions. Meanwhile, the McCormicks agreed to a stock dividend. This action helped mellow strife and augment their power. How did discord affect efficiency? The conventional answer centers on management along with expansion abroad, but that analysis is enhanced through study of seven brands and their local factories, pricing, and an antitrust consent decree. When a voting trust ran out its clock in 1912, conflict at International Harvester was receding. The firm’s record suggests various governance formats could yield efficiency and profitability.
Electronic health record (EHR) data have emerged as an important resource for population health and clinical research. There have been significant efforts to leverage EHR data for research; however, given data security concerns and the complexity of the data, EHR data are frequently difficult to access and use for clinical studies. We describe the development of a Clinical Research Datamart (CRDM) that was developed to provide well-curated and easily accessible EHR data to Duke University investigators.
The CRDM was designed to (1) contain most of the patient-level data elements needed for research studies; (2) be directly accessible by individuals conducting statistical analyses (including Biostatistics, Epidemiology, and Research Design (BERD) core members); (3) be queried via a code-based system to promote reproducibility and consistency across studies; and (4) utilize a secure protected analytic workspace in which sensitive EHR data can be stored and analyzed. The CRDM utilizes data transformed for the PCORnet data network, and was augmented with additional data tables containing site-specific data elements to provide additional contextual information.
We provide descriptions of ideal use cases and discuss dissemination and evaluation methods, including future work to expand the user base and track the use and impact of this data resource.
The CRDM utilizes resources developed as part of the Clinical and Translational Science Awards (CTSAs) program and could be replicated by other institutions with CTSAs.
Statistical literacy is essential in clinical and translational science (CTS). Statistical competencies have been published to guide coursework design and selection for graduate students in CTS. Here, we describe common elements of graduate curricula for CTS and identify gaps in the statistical competencies.
We surveyed statistics educators using e-mail solicitation sent through four professional organizations. Respondents rated the degree to which 24 educational statistical competencies were included in required and elective coursework in doctoral-level and master’s-level programs for CTS learners. We report competency results from institutions with Clinical and Translational Science Awards (CTSAs), reflecting institutions that have invested in CTS training.
There were 24 CTSA-funded respondents representing 13 doctoral-level programs and 23 master’s-level programs. For doctoral-level programs, competencies covered extensively in required coursework for all doctoral-level programs were basic principles of probability and hypothesis testing, understanding the implications of selecting appropriate statistical methods, and computing appropriate descriptive statistics. The only competency extensively covered in required coursework for all master’s-level programs was understanding the implications of selecting appropriate statistical methods. The least covered competencies included understanding the purpose of meta-analysis and the uses of early stopping rules in clinical trials. Competencies considered to be less fundamental and more specialized tended to be covered less frequently in graduate courses.
While graduate courses in CTS tend to cover many statistical fundamentals, learning gaps exist, particularly for more specialized competencies. Educational material to fill these gaps is necessary for learners pursuing these activities.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Why patients with psychosis use cannabis remains debated. The self-medication hypothesis has received some support but other evidence points towards an alleviation of dysphoria model. This study investigated the reasons for cannabis use in first-episode psychosis (FEP) and whether strength in their endorsement changed over time.
FEP inpatients and outpatients at the South London and Maudsley, Oxleas and Sussex NHS Trusts UK, who used cannabis, rated their motives at baseline (n = 69), 3 months (n = 29) and 12 months (n = 36). A random intercept model was used to test the change in strength of endorsement over the 12 months. Paired-sample t-tests assessed the differences in mean scores between the five subscales on the Reasons for Use Scale (enhancement, social motive, coping with unpleasant affect, conformity and acceptance and relief of positive symptoms and side effects), at each time-point.
Time had a significant effect on scores when controlling for reason; average scores on each subscale were higher at baseline than at 3 months and 12 months. At each time-point, patients endorsed ‘enhancement’ followed by ‘coping with unpleasant affect’ and ‘social motive’ more highly for their cannabis use than any other reason. ‘Conformity and acceptance’ followed closely. ‘Relief of positive symptoms and side effects’ was the least endorsed motive.
Patients endorsed their reasons for use at 3 months and 12 months less strongly than at baseline. Little support for the self-medication or alleviation of dysphoria models was found. Rather, patients rated ‘enhancement’ most highly for their cannabis use.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Perinatal depression is a depressive illness that affects 10–15% of women in the UK with an estimated cost of £1.8 billion/year. Zinc deficiency is associated with the development of mood disorders and zinc supplementation has been shown to help reduce the symptoms of depression. Women who are pregnant and breastfeeding are at risk of lower levels of zinc because of the high demand from the developing and feeding baby. However, studies in the perinatal period are limited. With a long-term aim of designing a randomised controlled trial (RCT) to examine if zinc supplementation reduces depressive symptoms in pregnant and lactating women;the objective of this review was to systematically evaluate previous RCTs assessing zinc supplementation and depressive symptoms, in order to establish a zinc dosing regimen with regards to Galenic formulation, unit dose and frequency. The review was conducted by independent reviewers in accordance with PRISMA guidelines and is registered at Prospero (CRD42017059205). The Allied and Complimentary Medicine, CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and Cochrane databases were searched since records began, with no restrictions, for intervention trials assessing Galenic formulation, unit dose and frequency of zinc supplementation to reduce the symptoms of depression. From a total of 66 identified records, 7 articles met the inclusion and exclusion criteria; all assessed the effect of zinc supplementation on mood. Risk of bias was independently assessed using the standard ‘Cochrane risk of bias tool’. Overall, 5 of the 7 papers were rated as high-quality trials; of the other two, one was rated poor and the other fair but both had a number of learning points. Preliminary findings indicate at the end of supplementing zinc, depression scores were reduced significantly. In one study, the Beck score decreased in the placebo group, but this reduction was not significant compared to the baseline. In two of the studies there was a significant correlation between serum zinc and self-reported mood questionnaires. Results also suggest that 25 mg zinc supplementation combined with antidepressant drugs can be effective in the treatment of major depression in women. This supports other work where researchers supplemented 25 mg of elemental zinc for 12 weeks or longer and found a reduction of symptoms in both pregnant and non-pregnant women. Thus, an early conclusion is that 25 mg of elemental zinc is an effective dose for improving low mood and is achievable in a trial setting.
The Colorado Twin Registry (CTR) is a population-based registry formed from birth and school records including twins born between 1968 and the present. Two previous reports on the CTR [Rhea et al., (2006). Twin Research and Human Genetics, 9, 941–949; Rhea et al., (2013).Twin Research and Human Genetics, 16, 351–357] covered developments in the CTR through 2012. This report briefly summarizes previously presented material on ascertainment and recruitment and the relationships between samples and studies, discusses developments since 2012 for four previously described twin samples, describes two new samples and their complementary studies and expands on two subjects briefly mentioned in the last report: a history of genotyping efforts involving CTR samples, and a survey of collaborations and consortia in which CTR twins have been included. The CTR remains an active resource for both ongoing, longitudinal research and the recruitment of new twin samples for newly identified research opportunities.
The purpose of this update is to provide the most current information about both the Colorado Adoption Project (CAP) and the Longitudinal Twin Study (LTS) and to introduce the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife), a product of their merger and a unique study of lifespan behavioral development and cognitive aging. The primary objective of CATSLife is to assess the unique saliency of early childhood genetic and environmental factors to adult cognitive maintenance and change, as well as proximal influences and innovations that emerge across development. CATSLife is currently assessing up to 1600 individuals on the cusp of middle age, targeting those between 30 and 40 years of age. The ongoing CATSLife data collection is described as well as the longitudinal data available from the earlier CAP and LTS assessments. We illustrate CATSLife via current projects and publications, highlighting the measurement of genetic, biochemical, social, sociodemographic and environmental indices, including geospatial features, and their impact on cognitive maintenance in middle adulthood. CATSLife provides an unparalleled opportunity to assess prospectively the etiologies of cognitive change and test the saliency of early childhood versus proximal influences on the genesis of cognitive decline.
Whole-grain cereal breakfast consumption has been associated with beneficial effects on glucose and insulin metabolism as well as satiety. Pearl millet is a popular ancient grain variety that can be grown in hot, dry regions. However, little is known about its health effects. The present study investigated the effect of a pearl millet porridge (PMP) compared with a well-known Scottish oats porridge (SOP) on glycaemic, gastrointestinal, hormonal and appetitive responses. In a randomised, two-way crossover trial, twenty-six healthy participants consumed two isoenergetic/isovolumetric PMP or SOP breakfast meals, served with a drink of water. Blood samples for glucose, insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide (GIP), peptide YY, gastric volumes and appetite ratings were collected 2 h postprandially, followed by an ad libitum meal and food intake records for the remainder of the day. The incremental AUC (iAUC2h) for blood glucose was not significantly different between the porridges (P > 0·05). The iAUC2h for gastric volume was larger for PMP compared with SOP (P = 0·045). The iAUC2h for GIP concentration was significantly lower for PMP compared with SOP (P = 0·001). Other hormones and appetite responses were similar between meals. In conclusion, the present study reports, for the first time, data on glycaemic and physiological responses to a pearl millet breakfast, showing that this ancient grain could represent a sustainable alternative with health-promoting characteristics comparable with oats. GIP is an incretin hormone linked to TAG absorption in adipose tissue; therefore, the lower GIP response for PMP may be an added health benefit.
The present research aimed to describe perceptions and behaviours around the consumption of water and sugar-sweetened beverages (SSB) by youths.
A formative, qualitative study which conducted four focus groups. Transcripts were analysed and themes related to reasons youths drink SSB and water, and conversely do not drink SSB and water, were analysed to reveal thematic clusters around sensory factors, environment and policy, access, marketing and role model influences, and health risks.
A rural, tri-ethnic community in New Mexico, USA.
Middle- and high-school students, parents and teachers.
Although youths and adults were aware of the health risks of soda, they did not translate this information to other SSB, including sports drinks and sweetened tea. Moreover, their perceptions of risks of dyes outweighed their concern with sugar. Youths and adults were aware of water’s health benefits, but they focused on short-term benefits. Youths and adults perceived water as unappealing. Adults were also concerned with water safety and access.
This formative research has implications for decreasing SSB consumption and simultaneously increasing water intake among youths in rural communities. Addressing unique access and safety concerns related to water in rural communities, as well as increasing awareness of the risks of all types of SSB, can work together in a positive feedback loop to change perceptions and behaviours with long-term health consequences. Specific policy suggestions include strengthening school policies to restrict all types of SSB and water promotion efforts that address access, safety and health benefits.
Geomorphic evidence of past glaciation, such as U-shaped valleys, aretes, glacial lakes, and moraines, is preserved in the highland surrounding Cerro Chirripó in the Cordillera de Talamanca, Costa Rica. Previous work to establish a glacial chronology has focused on relative age dating of moraines and on radiocarbon dating of basal lake sediments to infer the timing of deglaciation. We used cosmogenic 36Cl surface exposure dating to constrain the ages of moraines within two formerly glaciated valleys, the Morrenas and Talari valleys. Forty-nine boulder samples were processed and measured from four moraine complexes in the Morrenas Valley and two moraine complexes in the Talari Valley. The exposure ages of these samples indicate a major glacial event occurred in this area from ~25 to 23 ka, broadly synchronous with the global last glacial maximum. Our results also indicate periods of glacial retreats and standstills from the deglacial period to the Early Holocene (~16–10 ka) before the complete disappearance of glaciers in this highland. These findings provide important insights into the glacial chronology and paleoclimate of tropical America.
The drive to control neglected tropical diseases (NTDs) has had many successes but to reach defined targets new approaches are required. Over the last decade, NTD control programmes have benefitted from increased resources, and from effective partnerships and long-term pharmaceutical donations. Although the NTD agenda is broader than those diseases of parasitic aetiology there has been a massive up-scaling of the delivery of medicines to some billion people annually. Recipients are often the poorest, with the aspiration that NTD programmes are key to universal health coverage as reflected within the 2030 United Nations sustainable development goals (SDGs). To reach elimination targets, the community will need to adapt global events and changing policy environments to ensure programmes are responsive and can sustain progress towards NTD targets. Innovative thinking embedded within regional and national health systems is needed. Policy makers, managers and frontline health workers are the mediators between challenge and change at global and local levels. This paper attempts to address the challenges to end the chronic pandemic of NTDs and achieve the SDG targets. It concludes with a conceptual framework that illustrates the interactions between these key challenges and opportunities and emphasizes the health system as a critical mediator.
Multidrug-resistant organisms (MDROs) are increasingly reported in residential care homes for the elderly (RCHEs). We assessed whether implementation of directly observed hand hygiene (DOHH) by hand hygiene ambassadors can reduce environmental contamination with MDROs.
From July to August 2017, a cluster-randomized controlled study was conducted at 10 RCHEs (5 intervention versus 5 nonintervention controls), where DOHH was performed at two-hourly intervals during daytime, before meals and medication rounds by a one trained nurse in each intervention RCHE. Environmental contamination by MRDOs, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter species (CRA), and extended-spectrum β-lactamse (ESBL)–producing Enterobacteriaceae, was evaluated using specimens collected from communal areas at baseline, then twice weekly. The volume of alcohol-based hand rub (ABHR) consumed per resident per week was measured.
The overall environmental contamination of communal areas was culture-positive for MRSA in 33 of 100 specimens (33%), CRA in 26 of 100 specimens (26%), and ESBL-producing Enterobacteriaceae in 3 of 100 specimens (3%) in intervention and nonintervention RCHEs at baseline. Serial monitoring of environmental specimens revealed a significant reduction in MRSA (79 of 600 [13.2%] vs 197 of 600 [32.8%]; P<.001) and CRA (56 of 600 [9.3%] vs 94 of 600 [15.7%]; P=.001) contamination in the intervention arm compared with the nonintervention arm during the study period. The volume of ABHR consumed per resident per week was 3 times higher in the intervention arm compared with the baseline (59.3±12.9 mL vs 19.7±12.6 mL; P<.001) and was significantly higher than the nonintervention arm (59.3±12.9 mL vs 23.3±17.2 mL; P=.006).
The direct observation of hand hygiene of residents could reduce environmental contamination by MDROs in RCHEs.
Resolution of inflammation is an active process involving specialised pro-resolving mediators (SPM) generated from the n-3 fatty acids EPA and DHA. n-3 Fatty acid supplementation during pregnancy may provide an intervention strategy to modify these novel SPM. This study aimed to assess the effect of n-3 fatty acid supplementation in pregnancy on offspring SPM at birth and 12 years of age (12 years). In all, ninety-eight atopic pregnant women were randomised to 3·7 g daily n-3 fatty acids or a control (olive oil), from 20 weeks gestation until delivery. Blood was collected from the offspring at birth and at 12 years. Plasma SPM consisting of 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins, 17-hydroxydocosahexaenoic acid (17-HDHA), D-series resolvins, 14-hydroxydocosahexaenoic acid (14-HDHA), 10 S,17S-dihydroxydocosahexaenoic acid, maresins and protectin 1, were measured by liquid chromatography-tandem MS. We identified the resolvins RvE1, RvE2, RvE3, RvD1, 17R-RvD1 and RvD2 for the first time in human cord blood. n-3 Fatty acids increased cord blood 18-HEPE (P<0·001) derived from EPA relative to the control group. DHA-derived 17-HDHA at birth was significantly increased in the n-3 fatty acid group relative to the controls (P=0·001), but other SPM were not different between the groups. n-3 Fatty acid supplementation during pregnancy was associated with an increase in SPM precursors in the offspring at birth but the effects were not sustained at 12 years. The presence of these SPM, particularly at birth, may have functions relevant in the newborn that remain to be established, which may be useful for future investigations.
It is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from ‘fundamental’ (necessary for all) to ‘specialized’ (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.
We surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by ‘fundamental’ and ‘specialized.’
There were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one’s own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).
We have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature.
To study the association between gastrointestinal colonization of carbapenemase-producing Enterobacteriaceae (CPE) and proton pump inhibitors (PPIs).
We analyzed 31,526 patients with prospective collection of fecal specimens for CPE screening: upon admission (targeted screening) and during hospitalization (opportunistic screening, safety net screening, and extensive contact tracing), in our healthcare network with 3,200 beds from July 1, 2011, through December 31, 2015. Specimens were collected at least once weekly during hospitalization for CPE carriers and subjected to broth enrichment culture and multiplex polymerase chain reaction.
Of 66,672 fecal specimens collected, 345 specimens (0.5%) from 100 patients (0.3%) had CPE. The number and prevalence (per 100,000 patient-days) of CPE increased from 2 (0.3) in 2012 to 63 (8.0) in 2015 (P<.001). Male sex (odds ratio, 1.91 [95% CI, 1.15–3.18], P=.013), presence of wound or drain (3.12 [1.70–5.71], P<.001), and use of cephalosporins (3.06 [1.42–6.59], P=.004), carbapenems (2.21 [1.10–4.48], P=.027), and PPIs (2.84 [1.72–4.71], P<.001) in the preceding 6 months were significant risk factors by multivariable analysis. Of 79 patients with serial fecal specimens, spontaneous clearance of CPE was noted in 57 (72.2%), with a median (range) of 30 (3–411) days. Comparing patients without use of antibiotics and PPIs, consumption of both antibiotics and PPIs after CPE identification was associated with later clearance of CPE (hazard ratio, 0.35 [95% CI, 0.17–0.73], P=.005).
Concomitant use of antibiotics and PPIs prolonged duration of gastrointestinal colonization by CPE.