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The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.
Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6–51 and HR = 7.0, 95% CI 1.5–33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88–1.5) or diabetes (HR = 1.1, 95% CI 0.9–1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84–20) or general population (SIR: 1.9, 95% CI 1.0–3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.
Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described.
As uncertainty remains about whether clinical response influences cognitive function after electroconvulsive therapy (ECT) for depression, we examined the effect of remission status on cognitive function in depressed patients 4 months after a course of ECT.
A secondary analysis was undertaken on participants completing a randomised controlled trial of ketamine augmentation of ECT for depression who were categorised by remission status (MADRS ⩽10 v. >10) 4 months after ECT. Cognition was assessed with self-rated memory and neuropsychological tests of anterograde verbal and visual memory, autobiographical memory, verbal fluency and working memory. Patients were assessed through the study, healthy controls on a single occasion, and compared using analysis of variance.
At 4-month follow-up, remitted patients (N = 18) had a mean MADRS depression score of 3.8 (95% CI 2.2–5.4) compared with 27.2 (23.0–31.5) in non-remitted patients (N = 19), with no significant baseline differences between the two groups. Patients were impaired on all cognitive measures at baseline. There was no deterioration, with some measures improving, 4-months after ECT, at which time remitted patients had significantly improved self-rated memory, anterograde verbal memory and category verbal fluency compared with those remaining depressed. Self-rated memory correlated with category fluency and autobiographical memory at follow-up.
We found no evidence of persistent impairment of cognition after ECT. Achieving remission improved subjective memory and verbal memory recall, but other aspects of cognitive function were not influenced by remission status. Self-rated memory may be useful to monitor the effects of ECT on longer-term memory.
Scientific quality and feasibility are part of ethics review by Institutional Review Boards (IRBs). Scientific Review Committees (SRCs) were proposed to facilitate this assessment by the Clinical and Translational Science Award (CTSA) SRC Consensus Group. This study assessed SRC feasibility and impact at CTSA-affiliated academic health centers (AHCs).
SRC implementation at 10 AHCs was assessed pre/post-intervention using quantitative and qualitative methods. Pre-intervention, four AHCs had no SRC, and six had at least one SRC needing modifications to better align with Consensus Group recommendations.
Facilitators of successful SRC implementation included broad-based communication, an external motivator, senior-level support, and committed SRC reviewers. Barriers included limited resources and staffing, variable local mandates, limited SRC authority, lack of anticipated benefit, and operational challenges. Research protocol quality did not differ significantly between study periods, but respondents suggested positive effects. During intervention, median total review duration did not lengthen for the 40% of protocols approved within 3 weeks. For the 60% under review after 3 weeks, review was lengthened primarily due to longer IRB review for SRC-reviewed protocols. Site interviews recommended designing locally effective SRC processes, building buy-in by communication or by mandate, allowing time for planning and sharing best practices, and connecting SRC and IRB procedures.
The CTSA SRC Consensus Group recommendations appear feasible. Although not conclusive in this relatively short initial implementation, sites perceived positive impact by SRCs on study quality. Optimal benefit will require local or federal mandate for implementation, adapting processes to local contexts, and employing SRC stipulations.
Organic grain producers are interested in reducing tillage to conserve soil and decrease labor and fuel costs. We examined agronomic and economic tradeoffs associated with alternative strategies for reducing tillage frequency and intensity in a cover crop–soybean (Glycine max L. Merr.) sequence within a corn (Zea mays L.)–soybean–spelt (Triticum spelta L.) organic cropping system experiment in Pennsylvania. Tillage-based soybean production preceded by a cover crop mixture of annual ryegrass (Lolium perenne L. ssp. multiflorum), orchardgrass (Dactylis glomerata L.) and forage radish (Raphanus sativus L.) interseeded into corn grain (Z. mays L.) was compared with reduced-tillage soybean production preceded by roller-crimped cereal rye (Secale cereale L.) that was sown after corn silage. Total aboveground weed biomass did not differ between soybean production strategies. Each strategy, however, was characterized by high inter-annual variability in weed abundance. Tillage-based soybean production marginally increased grain yield by 0.28 Mg ha−1 compared with reduced-tillage soybean. A path model of soybean yield indicated that soybean stand establishment and weed biomass were primary drivers of yield, but soybean production strategy had a measurable effect on yields due to factors other than within-season weed–crop competition. Cumulative tillage frequency and intensity were quantified for each cover crop—sequence using the Soil Tillage Intensity Rating (STIR) index. The reduced-tillage soybean sequence resulted in 50% less soil disturbance compared to tillage-based soybean sequence across study years. Finally, enterprise budget comparisons showed that the reduced-tillage soybean sequence resulted in lower input costs than the tillage-based soybean sequence but was approximately $114 ha−1 less profitable because of lower average yields.
We present a workflow to track icebergs in proglacial fjords using oblique time-lapse photos and the Lucas-Kanade optical flow algorithm. We employ the workflow at LeConte Bay, Alaska, where we ran five time-lapse cameras between April 2016 and September 2017, capturing more than 400 000 photos at frame rates of 0.5–4.0 min−1. Hourly to daily average velocity fields in map coordinates illustrate dynamic currents in the bay, with dominant downfjord velocities (exceeding 0.5 m s−1 intermittently) and several eddies. Comparisons with simultaneous Acoustic Doppler Current Profiler (ADCP) measurements yield best agreement for the uppermost ADCP levels (~ 12 m and above), in line with prevalent small icebergs that trace near-surface currents. Tracking results from multiple cameras compare favorably, although cameras with lower frame rates (0.5 min−1) tend to underestimate high flow speeds. Tests to determine requisite temporal and spatial image resolution confirm the importance of high image frame rates, while spatial resolution is of secondary importance. Application of our procedure to other fjords will be successful if iceberg concentrations are high enough and if the camera frame rates are sufficiently rapid (at least 1 min−1 for conditions similar to LeConte Bay).
Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.
To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.
We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.
Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.
Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.
Declaration of interest
D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.
As demonstrated by neuroimaging data, the human brain contains systems that control responses to threat. The revised Reinforcement Sensitivity Theory of personality predicts that individual differences in the reactivity of these brain systems produce anxiety and fear-related personality traits. Here we discuss some of the challenges in testing this theory and, as an example, present a pilot study that aimed to dissociate brain activity during pursuit by threat and goal conflict. We did this by translating the Mouse Defense Test Battery for human fMRI use. In this version, dubbed the Joystick Operated Runway Task (JORT), we repeatedly exposed 24 participants to pursuit and goal conflict, with and without threat of electric shock. The runway design of JORT allowed the effect of threat distance on brain activation to be evaluated independently of context. Goal conflict plus threat of electric shock caused deactivation in a network of brain areas that included the fusiform and middle temporal gyri, as well as the default mode network core, including medial frontal regions, precuneus and posterior cingulate gyrus, and laterally the inferior parietal and angular gyri. Consistent with earlier research, we also found that imminent threat activated the midbrain and that this effect was significantly stronger during the simple pursuit condition than during goal conflict. Also consistent with earlier research, we found significantly greater hippocampal activation during goal conflict than pursuit by imminent threat. In conclusion, our results contribute knowledge to theories linking anxiety disorders to altered functioning in defensive brain systems and also highlight challenges in this research domain.
Structured, empirically supported psychological interventions are lacking for patients who require organ transplantation. This stage IA psychotherapy development project developed and tested the feasibility, acceptability, tolerability, and preliminary efficacy of an 8-week group cognitive behavioral stress management intervention adapted for patients with end-stage liver disease awaiting liver transplantation.
Twenty-nine English-speaking United Network for Organ Sharing–registered patients with end-stage liver disease from a single transplantation center enrolled in 8-week, group cognitive-behavioral liver stress management and relaxation training intervention adapted for patients with end-stage liver disease. Patients completed pre- and postintervention surveys that included the Beck Depression Inventory II and the Beck Anxiety Inventory. Feasibility, acceptability, tolerability, and preliminary efficacy were assessed.
Attendance rate was 69.40%. The intervention was rated as “good” to “excellent” by 100% of participants who completed the postintervention survey in teaching them new skills to relax and to cope with stress, and by 94.12% of participants in helping them feel supported while waiting for a liver transplant. No adverse events were recorded over the course of treatment. Attrition was 13.79%. Anxious and depressive symptoms were not statistically different after the intervention.
Significance of results
The liver stress management and relaxation training intervention is feasible, acceptable, and tolerable to end-stage liver disease patients within a transplant clinic setting. Anxious and depressive symptoms remained stable postintervention. Randomized controlled trials are needed to study the intervention's effectiveness in this population.
There is no recorded maize (Zea mays spp. mays) from sites predating circa cal AD 800 in the northern Lake Michigan or Lake Superior basins of the western Great Lakes, despite the presence of maize microbotanicals including phytoliths and starches in Michigan, New York, and Quebec as early as 400 cal BC. To evaluate the potential for an earlier maize presence in the northern Lake Michigan basin, samples of carbonized food residues adhering to 16 ceramic vessels were obtained from the Winter site (20DE17) located on the Garden Peninsula in the northern Lake Michigan basin. Each sample was split and sent to two analysts. Both analysts identified low incidences of maize starch and phytoliths in multiple samples, with overlapping identifications on several. Three direct accelerator mass spectrometry dates on the carbonized residues reveal maize incorporated into the residues as early as the second century cal BC, 800 years before any regional macrobotanical evidence. Although the method of dispersal cannot be determined, these results support the proposition that initial northern dispersal of maize in the region may have been nearly 800 years earlier than macrobotanical evidence would suggest and is consistent with the timing of its introduction to the lower Great Lakes area.
In southern Africa, wetlands of different types are an integral part of the drainage network, yet evolve and are sensitive to different combinations of geologic, climatic, geomorphic, edaphic and hydrologic controls. Understanding of these controls can help in the interpretation of environmental and climatic records from different wetland types, given that wetland sensitivity to environmental and climatic changes may vary throughout their ‘life cycle’. The chapter discusses inland wetland records from dated sites in South Africa in order to consider their significance for reconstructing late glacial and Holocene climates; and the relationship of wetlands to preservation of the Pleistocene archaeological record. Wetlands are sensitive to degradation under contemporary environmental and climatic changes, which may impact on their hydrological and ecological function as well as the integrity of associated archaeological sites.
Targeted surveillance has focused on device-associated infections and surgical site infections (SSIs) and is often limited to healthcare-associated infections (HAIs) in high-risk areas. Longitudinal trends in all HAIs, including other types of HAIs, and HAIs outside of intensive care units (ICUs) remain unclear. We examined the incidences of all HAIs using comprehensive hospital-wide surveillance over a 12-year period (2001–2012).
This retrospective observational study was conducted at the University of North Carolina (UNC) Hospitals, a tertiary care academic facility. All HAIs, including 5 major infections with 14 specific infection sites as defined using CDC criteria, were ascertained through comprehensive hospital-wide surveillance. Generalized linear models were used to examine the incidence rate difference by infection type over time.
A total of 16,579 HAIs included 6,397 cases in ICUs and 10,182 cases outside ICUs. The incidence of overall HAIs decreased significantly hospital-wide (−3.4 infections per 1,000 patient days), in ICUs (−8.4 infections per 1,000 patient days), and in non-ICU settings (−1.9 infections per 1,000 patient days). The incidences of bloodstream infection, urinary tract infection, and pneumonia in hospital-wide settings decreased significantly, but the incidences of SSI and lower respiratory tract infection remained unchanged. The incidence of Clostridium difficile infection (CDI) increased remarkably. The outcomes were estimated to include 700 overall HAIs prevented, 40 lives saved, and cost savings in excess of $10 million.
We demonstrated success in reducing overall HAIs over a 12-year period. Our data underscore the necessity for surveillance and infection prevention interventions outside of the ICUs, for non–device-associated HAIs, and for CDI.
Infect Control Hosp Epidemiol 2015;36(10):1139–1147
People who undergo hematopoietic stem cell transplantation are highly dependent on their caregiver during their lengthy treatment and recovery. The effectiveness of their caregiver's social support can profoundly affect their day-to-day treatment experiences and, in turn, how they recall those experiences and are affected by them long after the treatment ends.
Our participants were 182 men and women who had undergone a transplant within the previous 9 months to 3 years. They completed baseline measures (including a measure of caregiver social support effectiveness) and then completed three writing assignments describing their transplant experiences. Linguistic analyses were conducted to investigate their use of words indicating negative emotions, cognitive processing (insight and causation), and practical problems with money and insurance. Theory-based hypotheses predicted associations between specific functional types of caregiver support (emotional, informational, and instrumental) and these word categories.
As hypothesized, the effectiveness of different functional types of support from a caregiver were uniquely associated with theoretically relevant categories of word use. Structural equation models indicated that more effective caregiver emotional support predicted lower use of negative emotion words; more effective caregiver informational support predicted lower use of causation words; and more effective caregiver instrumental support predicted lower use of words related to money and insurance.
Significance of results:
Our findings provide insights to guide research on the mechanisms through which caregiver support influences patient outcomes after stem cell transplantation. For instance, research suggests that these kinds of effects could have implications for survivors' current self-concept, psychosocial functioning, and meaning-making.
Burn injuries are a common source of morbidity and mortality in the United States, with an estimated 450,000 burn injuries requiring medical treatment, 40,000 requiring hospitalization, and 3,400 deaths from burns annually in the United States. Patients with severe burns are at high risk for local and systemic infections. Furthermore, burn patients are immunosuppressed, as thermal injury results in less phagocytic activity and lymphokine production by macrophages. In recent years, multidrug-resistant (MDR) pathogens have become major contributors to morbidity and mortality in burn patients.
Since only limited data are available on the incidence of both device- and nondevice-associated healthcare-associated infections (HAIs) in burn patients, we undertook this retrospective cohort analysis of patients admitted to our burn intensive care unit (ICU) from 2008 to 2012.
To examine the micronutrient status of disadvantaged pre-schoolers from Northeast Brazil, following the introduction of pro-poor policies, by assessing the prevalence of anaemia and micronutrient deficiencies and the role of sociodemographic factors, genetic Hb disorders and parasitic infections.
In a cross-sectional study, data on sociodemographic status, health, growth, genetic Hb disorders, parasites and nutrient supply from day-care meals were obtained. Fasting blood samples were collected and analysed for Hb, serum ferritin, transferrin receptor, folate, vitamin B12, retinol, Zn and Se.
Pre-schoolers aged 3–6 years from disadvantaged households.
Of the 376 sampled children, 94 % were of black or mixed race; 33 % and 29 % had at least one genetic Hb disorder and intestinal parasite, respectively. Stunting and underweight were ≤5 %; 14 % were overweight. Day-care centres supplied micronutrient-dense meals and snacks each weekday. Less than 10 % of pre-schoolers had anaemia and micronutrient deficiencies. Predictors (P < 0·05) of Hb were α3·7 thalassaemia, Se and retinol (but not ferritin). Micronutrient predictors (P < 0·05) were: elevated α1-glycoprotein for ferritin, Hb AS and BMI Z-score >1 for transferrin receptor, Zn and elevated α1-glycoprotein for retinol, sex and helminths for Se, helminths for vitamin B12, and Giardia intestinalis infection for serum folate.
Impaired growth, anaemia and micronutrient deficiencies were uncommon among these disadvantaged pre-schoolers attending day care. A range of interventions including provision of micronutrient-dense, fortified day-care meals, deworming and vitamin A supplementation likely contributed to improved micronutrient status, suggesting expanded coverage of these programmes.