Adherence to Anticoagulation Interruption Guidelines in Patients with Atrial Fibrillation.

INTRODUCTION: Annually, 15% of patients who receive oral anticoagulation require interruption for surgery or an invasive procedure. This study evaluates the adherence of patients with atrial fibrillation with a history of stroke or transient ischemic attack to the Thrombosis Canada Perioperative guidelines for the discontinuation and reinitiation of anticoagulation treatment. METHODS: We collected data from a prospective patient survey at the Stroke Prevention Clinic in the University of Alberta hospital. Patients' charts were reviewed from the electronic medical records, and adherence was looked at according to the Thrombosis Canada Perioperative guidelines for the interruption of anticoagulants. RESULTS: During the study period (2016-2019), there were 509 patients surveyed. Anticoagulation treatment was interrupted in 150 patients with 98 interrupted for surgical or invasive procedures. The interruption was adherent to guidelines in only 29 (29.6%) of patients and inappropriate or nonadherent in 69 (70.4%) patients. There were seven ischemic strokes recorded during the period of interruption. The proportion of strokes was higher in patients whose anticoagulation interruption was longer than what the guidelines recommended (6/61 or 9.8%) when compared to those who adhered to recommended perioperative anticoagulation guidelines (1/29 or 3.4%). CONCLUSION: Our results indicate that significant discrepancy with following the recommended perioperative anticoagulation guidelines is common in real-life practice. Delay in re-anticoagulation may increase the risk of complications.

Early Recanalization With Alteplase in Stroke Because of Large Vessel Occlusion in the ESCAPE Trial.

BACKGROUND AND PURPOSE: Quantitating the effect of intravenous alteplase on the technical outcome of early recanalization of large vessel occlusions aids understanding. We report the prevalence of early recanalization in patients with stroke because of large vessel occlusion treated with and without intravenous alteplase and endovascular thrombectomy, and its association with clinical outcome. METHODS: Patients with acute ischemic stroke with large vessel occlusion from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial) were included in this post hoc analysis. Outcomes of interest were the prevalence of early recanalization (1) and good outcome (2), defined as modified Rankin Scale score of 0 to 2 at 90 days. RESULTS: Among 147 patients who did not receive endovascular thrombectomy, early recanalization occurred in 4/30 (13.3%) patients without and 48/117 (41.0%) patients with intravenous alteplase (adjusted risk ratios, 3.2 [95% CI, 1.2-8.1]). Good outcome was achieved by 34/116 (29.3%) of patients who received intravenous alteplase versus 10/29 (34.5%) who did not receive alteplase (adjusted risk ratios, 1.0 [95% CI, 0.6-1.5) and by 20/52 (38.5%) patients with versus 24/93 (25.8%) without early recanalization (adjusted risk ratios, 1.9 [95% CI, 1.2-2.9]). CONCLUSIONS: Early recanalization was confirmed as a strong predictor of good outcome in patients who did not undergo endovascular thrombectomy and was improved with intravenous alteplase, yet a majority of patients (59.0%) did not achieve early reperfusion. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Factors influencing the community integration of patients following traumatic spinal cord injury: a systematic review.

BACKGROUND: Spinal cord injury (SCI) is a high-cost disabling condition, which brings a huge number of changes in individual's life. The emphasis of rehabilitation has moved from medical administration to issues that affect quality of life and community integration. This systematic review was conducted to identify the factors associated with community reintegration of patients with spinal cord injury. . METHODS: Google Scholar, PEDro, Pakmedinet, AMED, BIOMED central, Cochrane Library, MEDLINE, PsychoINFO, PUBMED, ScienceDIRECT, Scirus and Wiley Online Library databses were searched by using key words 'Spinal cord injury' 'Paraplegia' or 'Spinal Cord Lesion' or Tetraplegia. They were cross-linked with 'Community reintegration', 'Community participation' and 'Community access'. The methodological quality of the studies included was analysed by using McMaster University Tool and Thomas Tool. The data extracted included sample size, intervention, duration, results, outcome measures, and follow-up period. RESULTS: A total of 11 relevant studies were located. The evidence extracted was classified into four groups; health-related barriers or facilitators, environment-related barriers or facilitators, psychological barriers and social barriers that are associated with community reintegration of such individuals. CONCLUSIONS: The review revealed that there were more barriers in the form of health-related issues, personal and environmental, psychological and social issues that hinder the community reintegration of individuals with spinal cord injury compared to facilitators. Most studies identified special challenges related to environment in the sense of accessibility of home and public buildings and transportation. Removing barriers related to health, environment, and psychological and social factors can enhance community reintegration of such patients.

Trends in Stroke Presentations before and during the COVID-19 Pandemic: A Meta-Analysis.

BACKGROUND AND PURPOSE: There are reports of decline in the rates of acute emergency presentations during coronavirus disease 2019 (COVID-19) pandemic including stroke. We performed a meta-analysis of the impact of COVID-19 pandemic on rates of stroke presentations and on rates of reperfusion therapy. METHODS: Following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines, we systematically searched the literature for studies reporting changes in stroke presentations and treatment rates before and during the COVID-19 pandemic. Aggregated data were pooled using meta-analysis with random-effect models. RESULTS: We identified 37 observational studies (n=375,657). Pooled analysis showed decline in rates of all strokes (26.0%; 95% confidence interval [CI], 22.4 to 29.7) and its subtypes; ischemic (25.3%; 95% CI, 21.0 to 30.0), hemorrhagic (27.6%; 95% CI, 20.4 to 35.5), transient ischemic attacks (41.9%; 95% CI, 34.8 to 49.3), and stroke mimics (45.6%; 95% CI, 33.5 to 58.0) during months of pandemic compared with the pre-pandemic period. The decline was most evident for mild symptoms (40% mild vs. 25%-29% moderate/severe). Although rates of intravenous thrombolytic (IVT) and endovascular thrombectomy (EVT) decreased during pandemic, the likelihood of being treated with IVT and EVT did not differ between the two periods, both in primary and in comprehensive stroke centers (odds ratio [OR], 1.08; 95% CI, 0.94 to 1.24 and OR, 0.95; 95% CI, 0.83 to 1.09, respectively). CONCLUSIONS: Rates of all strokes types decreased significantly during pandemic. It is of paramount importance that general population should be educated to seek medical care immediately for stroke-like symptoms during COVID-19 pandemic. Whether delay in initiation of secondary prevention would affect eventual stroke outcomes in the long run needs further study.

Screening of Toxoplasmosis in Owned and Stray Dogs of District Faisalabad, Pakistan through Latex Agglutination and Indirect ELISA.

INTRODUCTION: Toxoplasma gondii (an intracellular protozoan) causes toxoplasmosis in warm-blooded animals, including humans and dogs. The present study was carried out to investigate the seroprevalence of canine toxoplasmosis in the owned and stray populations of dogs in Faisalabad District, Punjab, Pakistan. MATERIALS AND METHODS: Commercially available Latex Agglutination Test (LAT) kits were used for the screening of samples (139 stray and 150 owned), followed by confirmation through ELISA. For the statistical analyses, chi-square was used to correlate the prevalence of toxoplasmosis with various factors. RESULTS: The overall prevalence of toxoplasmosis, determined by the LAT, was 22.5% and, by ELISA, was 21.8%. A nonsignificant association of toxoplasmosis was determined among owned and stray dogs. Among owned dog breeds, Bulldogs showed 28.30% prevalence, and among stray dogs, the highest prevalence was determined in Bhakarwal dogs (39.29%). Young and female dogs showed a slightly higher prevalence of toxoplasmosis than adults and males, respectively. CONCLUSIONS: The present study determined by LAT and ELISA in owned dogs showed the same results, while a little variation was found in the stray dogs. It is concluded that both owned and stray dogs are infected with toxoplasmosis in Faisalabad District, and based on this, it is recommended that province-wide epidemiological studies be carried out to examine the prevalence of Toxoplasma and develop policies in order to control toxoplasmosis.

White matter hyperintensities in patients with Parkinson's disease: A systematic review and meta-analysis.

INTRODUCTION: Mechanisms driving neurodegeneration in Parkinson's disease (PD) are unclear and neurovascular dysfunction may be a contributing factor. White matter hyperintensities (WMH) are commonly found on brain MRI in patients with PD. It is controversial if they are more prevalent or more severe in PD compared with controls. This systematic review aims to answer this question. METHODS: A systematic search of electronic databases was conducted for studies of WMH in patients with PD. A qualitative synthesis was done for studies reporting WMH prevalence or WMH scores on a visual rating scale (VRS). In studies reporting total WMH volume, the difference between patients with PD and controls was pooled using random effects meta-analysis. RESULTS: Among 3860 subjects from 24 studies, 2360 were cases and 1500 controls. Fifteen studies reported WMH scores and four studies reported the prevalence of WMH. On VRS, five studies reported no difference in WMH scores, three found higher WMH scores in PD compared to controls, three reported increased WMH scores either in periventricular or deep white matter, and four reported higher scores only in PD with dementia. In studies reporting WMH volume, there was no difference between patients with PD and controls (pooled standardized mean difference = 0.1, 95%CI: -0.1-0.4, I2 = 81%). CONCLUSION: WMH are not more prevalent or severe in patients with PD than in age-matched controls. PD dementia may have more severe WMH compared to controls and PD with normal cognition. Prospective studies using standardized methods of WMH assessment are needed.

Pre-hospital triage of suspected acute stroke patients in a mobile stroke unit in the rural Alberta.

Mobile Stroke Unit (MSU) expedites the delivery of intravenous thrombolysis in acute stroke patients. We further evaluated the functional outcome of patients shipped to a tertiary care centre or repatriated to local hospitals after triage by MSU in acute stroke syndrome in rural northern Alberta. Consecutive patients with suspected acute stroke syndrome were included. On the basis of neurology consultation and, Computed Tomography findings, patients, who were thrombolysed or needed advanced care were transported to the Comprehensive stroke center (CSC) (Triage to CSC group). Other patients were repatriated to local hospital care (Triage to LHC group). A total of 156 patients were assessed in MSU, 73 (46.8%) were female and the mean age was 66.6 ± 15 years. One hundred and eight (69.2%) patients, including 41 (26.3%) treated with thrombolysis were transported to the CSC (Triage to CSC group) and 48 (30.8%) were repatriated to local hospital care. The diagnosis made in MSU and final diagnosis were matching in 88% (95) and 91.7% (44, p = 0.39) in Triage to CSC and Triage to LHC groups respectively. Prehospital triage by MSU of acute stroke syndrome can reliably repatriate patients to the home hospital. The proposed model has the potential to triage patients according to their medical needs by enabling treatment in home hospitals whenever reasonable.

Construction and Analysis of a Novel Wearable Assistive Device for a Visually Impaired Person.

In this paper, we have given the design and development of a new wearable device that assists visually impaired individuals to travel independently and confidently. The newly proposed device is based on range-based sensors and would work effectively in both indoor and outdoor conditions. It is constructed in the form of two separate modules; one module is designed such that it can be attached to the waist belt of the user, and the other module is designed to wear it on ankle of the user. Both the modules communicate with each other using wireless communication and can cover the full front environment of the user. The information about the front environment is transmitted to the user, via headphone, by sending a set of voice instructions, stored in a memory card added in the belt module. In order to use the device in crowd mode, appropriate networking techniques were also implemented in the prototype such that the interference of two or more devices in the close vicinity can be avoided. In the end, effectiveness of the device is analyzed and proved by conducting experiments and obtaining statistical results.

Circulating microRNA in cardiovascular disease.

Acute myocardial infarction (AMI) and heart failure (HF) are two major causes of cardiovascular mortality and morbidity. Early diagnosis of these conditions is essential to instigate immediate treatment that may result in improved outcomes. Traditional biomarkers of AMI include cardiac troponins and other proteins released from the injured myocardium but there are a number of limitations with these biomarkers especially with regard to specificity. In the past few years circulating nucleic acids, notably microRNA that are small non-coding RNAs that regulate various cellular processes, have been investigated as biomarkers of disease offering improved sensitivity and specificity in the diagnosis and prognostication of various conditions. In this review, the role of microRNAs as biomarkers used in the diagnosis of AMI and HF is discussed, their advantage over traditional biomarkers is outlined and the potential for their implementation in clinical practice is critically assessed.

Circulating nucleic acids in plasma and serum: recent developments.

Nucleic acids (DNA and RNA) have been detected in plasma, serum, urine, and other body fluids from healthy subjects as well as in patients. The ability to detect and quantitate specific DNA and RNA sequences has opened up the possibility of diagnosis and monitoring of diseases. With the recent developments in the field of circulating nucleic acids the application in the diagnostic field has increased. The recent discovery of epigenetic changes in placental/fetal DNA and the detection of fetal/placental-specific RNAs have made it possible to use this technology in all pregnancies irrespective of the gender of the fetus. With the application of mass spectrometry and other techniques to this field, it is now possible to detect very small amounts of specific DNA in the presence of excess of other nonspecific nucleic acids (e.g., detection of mutations in fetal DNA in the presence of excess of maternal DNA). Circulating nucleic acids have now been shown to be useful in other conditions, such as diabetes mellitus, trauma, stroke, and myocardial infarction. In oncology, detection and monitoring of tumors is now possible by the detection of tumor-derived nucleic acids. In spite of these advances questions regarding the origin and biologic significance of circulating nucleic acids remain to be answered. Furthermore pre-analytical and analytical aspects of this field remain to be standardized.

Circulating nucleic acids and diabetic complications.

Diabetes mellitus is a major health problem across the world. Diabetic retinopathy (DR) and nephropathy are two of the major complications of diabetes. DR is the leading cause of blindness and diabetic nephropathy is the leading cause of end-stage renal failure. We have examined the potential value of circulating nucleic acids in the detection and monitoring of these two complications of diabetes. mRNA for nephrin was significantly higher in all diabetics compared to healthy controls and it was significantly higher in normoalbuminuric patients compared to healthy controls. This may indicate progression to microalbuminuric stage. Circulating rhodopsin mRNA was detectable in healthy subjects and in diabetic patients. It was significantly raised in diabetic patients with retinopathy. Higher rhodopsin mRNA in diabetic patients without retinopathy suggests that some of them may go on to develop it or already have it subclinically. Circulating nucleic acids have the potential to be noninvasive molecular tests for diabetic complications.

Real-time quantitative PCR measurement of thyroglobulin mRNA in peripheral blood of thyroid cancer patients and healthy subjects.

Follow-up of recurrent differentiated thyroid carcinoma involves the measurement of serum thyroglobulin (Tg). However, Tg autoantibodies are present in a high proportion of thyroid carcinoma patients (up to 25%) and these can interfere with the Tg immunoassays. To overcome this obstacle, investigators have used real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to measure Tg mRNA in the blood of patients with differentiated thyroid cancer, with varying degrees of success. In the present study, we demonstrate the first reported use of the PAXgene Blood RNA collection tube and extraction kit method for the preparation of RT-PCR-quality RNA with subsequent deployment of the latter in the development of a specific, sensitive, and reproducible Taqman assay for the detection and quantification of thyroglobulin mRNA. Beta-actin mRNA was also assayed and results are expressed as a ratio of Tg to beta-actin mRNA. The intra-assay coefficient of variations (CVs) for Tg and beta-actin mRNA assay were 27.7% and 25.4%, respectively. Inter-assay CVs were 20.8% and 28.8%, respectively, for the two assays. Tg mRNA was detected in all cancer subjects (n = 42) and healthy individuals (n = 20). Tg mRNA was significantly higher in cancer patients than in the healthy subjects (0.00169 +/- 0.00013 vs. 0.00051 +/- 0.00015; P<0.0001). Fourteen cancer patients had detectable levels of serum Tg, and Tg mRNA levels tended to be higher in these than in cancer subjects with undetectable serum Tg (0.00188 +/- 0.00021 vs. 0.00157 +/- 0.000178; P = 0.08). Circulatory Tg mRNA measurement may serve a useful role in the assessment of thyroid cancer.

Real-time quantitative PCR measurement of circulatory rhodopsin mRNA in healthy subjects and patients with diabetic retinopathy.

Diabetic retinopathy is the commonest complication of diabetes and is the biggest single cause of registered blindness in the UK. No biochemical tests exist to determine the precise state and rate of change of the eyes in the diabetic patient. In the present study, using real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we measured mRNA encoding the retina-specific pigment protein rhodopsin (RHO) in the peripheral blood of healthy individuals (n = 20) and diabetic patients (n = 46) with and without retinopathy. Beta-actin mRNA was also assayed and results are expressed as a ratio of RHO to beta-actin mRNA. Peripheral blood was taken by venipucture directly into PAXgene Blood RNA collection tubes and RNA extracted by use of the PAXgene Blood RNA extraction kit, as per the manufacturer's (Qiagen) instructions. Diabetic patients were divided into three groups defined by the severity of retinopathy as assessed by fundoscopy: A, diabetic without retinopathy; B, background retinopathy; and C, preproliferative retinopathy. Medians of the ratios between groups were compared. RHO mRNA was successfully detected and quantified in peripheral blood in all healthy and diabetic groups, with levels shown to be significantly higher in diabetic patients than in healthy controls (2.54 x 10(-5) vs. 1.29 x 10(-5); P = 0.002). Significant differences in RHO mRNA levels were also seen between healthy control subjects and diabetic groups A (2.52 x 10(-5); P = 0.022), B (1.98 x 10(-5); P = 0.028), and C (5.08 x 10(-5); P = 0.002). The results suggest that there is an increase in circulatory RHO mRNA with the severity of diabetic retinopathy.

Role of cell-free plasma DNA as a diagnostic marker for prostate cancer.

Recent evidence has shown elevated levels of cell-free plasma DNA in cancer patients. The aim of the present study was to quantify and compare the levels of cell-free plasma DNA in patients with prostate cancer, prostatic intraepithelial neoplasia (PIN), and benign prostatic hypertrophy (BPH) to examine if it offered a useful diagnostic test. Blood samples were obtained from 37 patients attending a clinic for prostate biopsies. Samples were taken prior to biopsy, within 1 hour of the biopsy, and then 2 weeks later. DNA was extracted using a QIAamp blood kit (Qiagen) and plasma DNA measured, in genome equivalents/milliliter plasma (GE/mL), using real-time quantitative PCR for the beta-globin gene. Prior to biopsy, plasma DNA concentration in BPH patients was 936 GE/mL (median; range: 633-2074 GE/mL), while cancer and PIN patients had significantly higher levels of DNA at 1734 GE/mL (median; range: 351-3131 GE/mL; P = 0.01) and 1780 GE/mL (median; range: 1514-2732 GE/mL; P = 0.04), respectively. Comparison of plasma DNA concentration before and after biopsy showed that 60 minutes after biopsy values were significantly higher in both BPH (1494 GE/mL; range: 613-2522 GE/mL; P = 0.029) and cancer (2758; range: 1498-5226 GE/mL; P = 0.007) patients. ROC analysis of the data indicated a sensitivity of 85% and a specificity of 73% when DNA concentration of 1000 GE/mL was taken as an indicator of malignancy or PIN. The data suggest that quantification of cell-free plasma DNA may have an important diagnostic role in distinguishing benign and malignant prostate disease.

Overview of circulating nucleic acids in plasma/serum.

The existence of circulating nucleic acids in plasma and serum (CNAPS) was first described almost six decades ago. However, the prognostic and diagnostic utility of this circulating DNA/RNA has only really begun to be appreciated in the last decade. Earlier studies concentrated mainly on investigations concerned with fetal medicine and oncology, and significant progress was made in both specialities. More recently the field of enquiry has extended further, and attention has turned to other pathologic states, including trauma, sepsis, myocardial infarction, stroke, transplantation, diabetes mellitus, and hematologic disorders. In some of these studies, mitochondrial as well as genomic DNA and tissue-specific mRNA have been analyzed, either quantitatively or qualitatively or both, and have been shown to be modified in the presence of disease. While there is tremendous potential for CNAPS as a clinical modality, many of the emerging studies seem to be confined to a few dedicated labs. Therefore, additional independent studies are necessary in some cases in order to show reproducibility, which will further consolidate the field. Despite this shortcoming, and with the evidently increasing number of applications for CNAPS, it is highly likely that routine testing, as described, will become reality within the next 5 to 10 years.

Circulating 11beta-hydroxysteroid dehydrogenase type 1 mRNA and cardiovascular risk factors.

11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been implicated in the pathogenesis of central obesity and metabolic syndrome. It has been shown that tissue-specific mRNA is present in blood, raising the possibility that quantifiable levels of 11beta-HSD1 mRNA may also be present in circulation. The aim of this study was to determine whether a relationship exists between circulating 11beta-HSD1 mRNA levels and various cardiovascular risk factors. Whole blood was collected using PAXgene Blood RNA tubes from 73 subjects. Total RNA was extracted, reverse-transcribed to cDNA, and 11beta-HSD1 mRNA was measured by quantitative real time PCR. The median BMI was 24 (range = 17-36) and the concentration of 11beta-HSD1 mRNA tended to decrease with increasing BMI (r=-0.206; P= 0.08). Multiple linear regression analysis identified BMI as an independent predictor of mRNA levels (beta=-0.412, P= 0.002). Other factors included in the analysis are age (beta= 0.952, P < 0.001), smoking (beta=-0.228, P= 0.027), alcohol intake (beta= 0.479, P < 0.001), and duration of menopause (beta=-1.602, P < 0.001). The results suggest a net decrease in systemic expression of 11beta-HSD1 with increased smoking, BMI, and duration of menopause. Increased systemic expression is seen with increasing age and alcohol intake.

Effect of hypoxia on circulating levels of retina-specific messenger RNA in type 2 diabetes mellitus.

Previously it was shown that the circulating rhodopsin mRNA level was higher in diabetic retinopathy (DR). Recent evidence suggests that hypoxia may also be associated with DR. The aim of this study was to investigate the effect of oxygen desaturation on circulating retina-specific mRNA in type 2 diabetic patients. Thirty-five type 2 diabetic patients underwent overnight oximetry. Two parameters from oximetry were used to measure oxygen desaturation: the number of times per hour the oxygen saturation decreased by 4% or greater (number of dips/hr) and percentage of sleep time with oxygen saturation (SpO(2)) <90%. Blood samples were collected into PAXgene Blood RNA tubes. Total RNA was extracted from the samples and reverse-transcribed into cDNA, and retina-specific markers were measured by quantitative real time PCR. In patients with >/=5 dips/hr, mRNA values for rhodopsin (P= 0.05) and RPE65 (P= 0.044) were significantly higher than in patients with <5 dips/hr. No change was seen in retinoschisin mRNA expression. In patients with preproliferative or proliferative DR, median levels for rhodopsin mRNA and RPE65 mRNA were 30% and 80% higher and retinoschisin mRNA was lower in patients with >/=5 dips/hr when compared to patients with <5 dips/hr. These results indicate that hypoxia may modulate expression of genes in the retina.