Applying the 4Ps of social marketing to retain and engage participants in longitudinal cohort studies: generation 2 Raine study participant perspectives.

BACKGROUND: Investigations of participant retention in longitudinal health and medical research, document  strategies that work best but overlook social marketing's capacity to influence participant retention. After applying the social marketing framework: the idea that determining what longitudinal participants 'buy' (product), at what cost (price), in what location (place) and through which communication channels (promotion),  this paper  aims to inform and enhance retention efforts. METHODS: This qualitative study was conducted through in-depth interviews with participants from the Raine Study that began in Western Australia in 1989. The Generation 2 participants, initially enrolled into the Raine Study as babies by their parents (Generation 1), are now young adults invited to attend follow-up studies and tests every few years. Our study defined 'active' participants (n = 17) as those who agreed to attend their 27 year follow-up, and 'inactive' (n = 12) participants as those who had attended neither of the past two follow-ups (22 and 27 years). RESULTS: Raine Study participants experienced core, actual and augmented product benefits. Inactive participants focused on the costs (price) associated with participation, and were more likely to suggest tele-health (place) strategies to overcome barriers to follow-up attendance. Both active and inactive participants found professional processes and friendly staff made the Raine Study environment appealing, suggested that social media (promotion) was underutilised, and offered novel ideas to enhance engagement. CONCLUSIONS: Social marketing can support the development of differentiated strategies addressing the unique needs and wants of active and inactive participants. Sophisticated cohort segmentation can reach participants in a more meaningful way, reinforce the study 'brand' and guard against attrition.

Plasmodium yoelii Uses a TLR3-Dependent Pathway to Achieve Mammalian Host Parasitism.

Malaria is associated with complicated immunopathogenesis. In this study, we provide evidence for an unexpected role of TLR3 in promoting the establishment of Plasmodium yoelii infection through delayed clearance of parasitemia in wild type C57BL/6jRj (B6) compared with TLR3 knockout mice. In this study, we confirmed an increased expression of Tlr3, Trif, Tbk1, and Irf7/Irf3 in the liver 42 h postinfection and the initiation of an early burst of proinflammatory response such as Ifng, NF-kB, and Tnfa in B6 mice that may promote parasite fitness. Interestingly, in the absence of TLR3, we showed the involvement of high IFN-γ and lower type I IFN response in the early clearance of parasitemia. In parallel, we observed an increase in splenic NK and NKT cells expressing TLR3 in infected B6 mice, suggesting a role for TLR sensing in the innate immune response. Finally, we find evidence that the increase in the frequency of CD19+TLR3+ B cells along with reduced levels of total IgG in B6 mice possibly suggests the initiation of TLR3-dependent pathway early during P. yoelii infection. Our results thus reveal a new mechanism in which a parasite-activated TLR3 pathway promotes blood stage infection along with quantitative and qualitative differences in Ab responses.

Diffusion-Weighted Imaging Hyperintensities in Subtypes of Acute Intracerebral Hemorrhage: Meta-Analysis.

Background and Purpose- Diffusion-weighted imaging (DWI) hyperintensities in intracerebral hemorrhage (ICH) are associated with increased risk of recurrent ICH, cognitive impairment, and death, but whether these lesions are specific to a subtype of ICH remains uncertain. We investigated the association between DWI lesions and ICH subtype and explored the risk factors for DWI lesions. Methods- In a systematic review of ICH studies, we identified those reporting prevalence of DWI lesions. Two reviewers independently assessed study eligibility and risk of bias and collected data. We determined the pooled prevalence of DWI lesions within 90 days after ICH onset for cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH using random-effects meta-analysis. We calculated odds ratios to compare prevalence of DWI lesions by ICH subtype and to assess risk factors for DWI lesions. Results- Eleven studies (1910 patients) were included. The pooled prevalence of DWI lesions was 18.9% (95% CI, 11.1-26.7) in cerebral amyloid angiopathy- and 21.0% (95% CI, 15.3-26.6) in hypertensive angiopathy-related ICH. There was no difference in the prevalence of DWI lesions between cerebral amyloid angiopathy- (64/292 [21.9%]) and hypertensive angiopathy-related ICH (79/370 [21.4%]; odds ratio, 1.25; 95% CI, 0.73-2.15) in the 5 studies reporting data on both ICH pathogeneses. In all ICH, presence of DWI lesions was associated with neuroimaging features of microangiopathy (leukoaraiosis extension, previous ICH, and presence, and number of microbleeds) but not with vascular risk factors or the use of antithrombotic therapies. Conclusions- Prevalence of DWI lesions in acute ICH averages 20%, with no difference between cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH. Detection of DWI lesions may add valuable information to assess the progression of the underlying microangiopathy.

Combining Standard Conventional Measures and Ecological Momentary Assessment of Depression, Anxiety and Coping Using Smartphone Application in Minor Stroke Population: A Longitudinal Study Protocol.

Context: Stroke has several consequences on survivors' daily life even for those who experience short-lasting neurological symptoms with no functional disability. Depression and anxiety are common psychological disorders occurring after a stroke. They affect long-term outcomes and quality of life but they are difficult to diagnose because of the neurobiological consequences of brain lesions. Current research priority is given to the improvement of the detection and prevention of those post-stroke psychological disorders. Although previous studies have brought promising perspectives, their designs based on retrospective tools involve some limits regarding their ecological validity. Ecological Momentary Assessment (EMA) is an alternative to conventional instruments that could be a key in research for understanding processes that underlined post-stroke depression and anxiety onset. We aim to evaluate the feasibility and validity of anxiety, depression and coping EMA for minor stroke patients. Methods: Patients hospitalized in an Intensive Neuro-vascular Care Unit between April 2016 and January 2017 for a minor stroke is involved in a study based on an EMA methodology. We use a smartphone application in order to assess anxiety and depression symptoms and coping strategies four times a day during 1 week at three different times after stroke (hospital discharge, 2 and 4 months). Participants' self-reports and clinician-rates of anxiety, depression and coping are collected simultaneously using conventional and standard instruments. Feasibility of the EMA method will be assessed considering the participation and compliance rate. Validity will be the assessed by comparing EMA and conventional self-report and clinician-rated measures. Discussion: We expect this study to contribute to the development of EMA using smartphone in minor stroke population. EMA method offers promising research perspective in the assessment and understanding of post-stroke psychological disorders. The development of EMA in stroke population could lead to clinical implications such as remotely psychological follow-ups during early supported discharge. Trial registration: European Clinical Trials Database Number 2014-A01937-40.

Heme dampens T-cell sequestration by modulating glial cell responses during rodent cerebral malaria.

Cerebral malaria is the deadliest complication of Plasmodium falciparum infection. Its pathophysiology is associated with a strong pro-inflammatory reaction and the activation of glial cells. Among modulators released during the infection, heme seems to play a controversial role in the pathophysiology of malaria. Herein, we first investigated the phenotype of glial cells during cerebral malaria in C57BL/6 mice infected with P. berghei ANKA. Given the fact that high levels of heme were associated with cerebral malaria, we then investigated its impact on microglial, astrocyte, and T cell responses to further clarify its contribution in the neuropathophysiology. Surprisingly, we found that administration of heme twice a day from day three of infection induced the expression of the Heme oxygenase-1 (Hmox1) gene and prevented brain damages. More specifically, heme inhibited the M1 phenotype of microglia, hampered the activation of astrocytes, and decreased the cerebral expression of Ifng, Tnfa and Ip10. Heme might that way alter the migration of pathogenic CD4 and CD8 T lymphocytes within the brain observed during cerebral malaria. Taking into account that cerebral malaria results from a complex interplay between host- and parasite-derived factors, it is possible that genetic polymorphisms of Hmox1, which could be associated with the control of systemic levels of heme during P. falciparum infection, might explain its dual role and its contribution to the resistance to cerebral malaria.

Detection of occult atrial fibrillation by pacemaker interrogation in cryptogenic stroke.

PURPOSE: Atrial fibrillation (AF) is a major cause of ischemic strokes, and it is assumed that occult intermittent episodes of AF are responsible for some of the seemingly cryptogenic strokes. Cardiac pacemakers feature rhythm diagnostic capabilities and data storage. We investigated whether pacemaker memory interrogation led to identification of undetected AF episodes prior to cryptogenic strokes. METHODS: The study enrolled all patients admitted between June 2010 and July 2013 for an acute cryptogenic stroke and who were implanted with a permanent pacemaker. Patients with a history of AF and a history of stroke with an identifiable origin were excluded. Pacemaker memories were interrogated to determine the presence of AF prior to the stroke and its temporal relationship with the stroke. RESULTS: Fourteen patients (nine men and five women) with a median (interquartile range) age of 84.5 (82.25-87.5) years were included. Median CHADS2 and CHA2DS2-VASc scores were 2 (1-2.75) and 3.5 (3-4), respectively. Pacemaker memories were activated in 13 patients with atrial arrhythmia detection based on an atrial cutoff rate in 8 patients and on the detection of atrial rate acceleration in 5 patients. Electrograms were available for review in 10 patients. Unknown AF or atrial flutter was diagnosed previous to the stroke in six (43 %) patients. Four patients experienced more than one arrhythmia episode. The last episode occurred in the 48 h prior to stroke in three patients and in the previous 4 weeks in five patients. Anticoagulation was started after the stroke in all of these six patients. CONCLUSIONS: Pacemaker interrogation has a high diagnostic yield in seemingly cryptogenic stroke, with frequent detection of occult AF. The causal link between AF and stroke is convincingly reinforced by their close temporal proximity, and anticoagulation is warranted in this clinical situation.

Validation of a new language screening tool for patients with acute stroke: the Language Screening Test (LAST).

BACKGROUND AND PURPOSE: Standard aphasia scales such as the Boston Diagnosis Aphasia Evaluation are inappropriate for use in acute stroke. Likewise, global stroke scales do not reliably detect aphasia, and existing brief aphasia screening scales suitable for patients with stroke have several limitations. The objective of this study was to generate and validate a bedside language screening tool, the Language Screening Test, suitable for use in the emergency setting. METHODS: The Language Screening Test comprises 5 subtests and a total of 15 items. To avoid retest bias, we created 2 parallel versions of the scale. We report the equivalence of the 2 versions, their internal and external validity, and their interrater reliability. We validated the scale by administering it to 300 consecutive patients within 24 hours after admission to our stroke unit and to 104 stabilized patients with and without aphasia using the Boston Diagnosis Aphasia Evaluation as a reference. RESULTS: The 2 versions of the Language Screening Test were equivalent with an intraclass correlation coefficient of 0.96. Internal validity was good; none of the items showed a floor or ceiling effect with no redundancy and good internal consistency (Cronbach α 0.88). External validation against the Boston Diagnosis Aphasia Evaluation showed a sensitivity of 0.98 and a specificity of 1. Interrater agreement was near perfect (intraclass correlation coefficient, 0.998). The median time to complete the Language Screening Test was approximately 2 minutes. Importantly, the Language Screening Test does not need to be administered by a speech and language therapist. CONCLUSIONS: This comprehensively validated language rating scale is simple and rapid, making it a useful tool for bedside evaluation of patients with acute stroke in routine clinical practice.

Watershed infarctions are more prone than other cortical infarcts to cause early-onset seizures.

BACKGROUND: Early-onset seizures(ESs) have been reported in 2% to 6% of strokes. Most previous studies have been retrospective and did not systematically perform cerebral magnetic resonance imaging (MRI). OBJECTIVE: To determine the prevalence and determinants of ESs in a prospective cohort. DESIGN: Prospective cohort study. SETTING: Stroke unit in an academic hospital. PATIENTS: Six hundred sixty-one consecutive individuals admitted to our stroke unit during an 18-month period for suspected stroke. MAIN OUTCOME MEASURES: Initial investigations systematically included cerebral MRI. Among patients with MRI-confirmed cerebral infarction, individuals with ES, defined as occurring within 14 days of stroke, were identified. RESULTS: Three hundred twenty-eight patients had MRI-confirmed cerebral infarcts and 178 had cortical involvement. The ESs, all initially partial seizures, occurred in 14 patients (4.3%) and at stroke onset in 5 patients. The ESs occurred exclusively in patients with cortical involvement (P <.001). With infarcts involving the cerebral cortex, there was a higher risk of ESs in watershed infarctions than in territorial strokes (6 of 26 [23.1%] vs 8 of 152 [5.3%], P = .007). Logistic regression analysis showed an almost 4-fold increased risk of ES in patients with watershed infarctions compared with other cortical infarcts (odds ratio, 4.7; 95% confidence interval, 1.5- 15.4; P = .01). Age, sex, diabetes mellitus, hypertension, smoking, National Institutes of Health Stroke Scale score, and cardioembolic origin were not significant risk factors for ES. CONCLUSIONS: The cortical hemispheric location of ischemic strokes is associated with a higher risk of ES. Among these patients, the watershed mechanism is a strong and independent determinant of stroke-related ES.

Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD.

There is increasing evidence that genetic variants of mitochondrial DNA have an important role in the cause of idiopathic Parkinson's disease. We determined the mitochondrial DNA haplogroup of 455 Parkinson's disease cases, 185 Alzheimer's disease cases, and 447 healthy English control subjects. The UKJT haplogroup cluster was associated with a 22% reduction in population-attributable risk for Parkinson's disease. There was no association between individual haplogroups or the UKJT cluster and Alzheimer's disease, confirming that the association with Parkinson's disease was disease specific and not a general effect seen in all neurodegenerative diseases.