Development and validation of machine learning algorithms based on electrocardiograms for cardiovascular diagnoses at the population level.

Artificial intelligence-enabled electrocardiogram (ECG) algorithms are gaining prominence for the early detection of cardiovascular (CV) conditions, including those not traditionally associated with conventional ECG measures or expert interpretation. This study develops and validates such models for simultaneous prediction of 15 different common CV diagnoses at the population level. We conducted a retrospective study that included 1,605,268 ECGs of 244,077 adult patients presenting to 84 emergency departments or hospitals, who underwent at least one 12-lead ECG from February 2007 to April 2020 in Alberta, Canada, and considered 15 CV diagnoses, as identified by International Classification of Diseases, 10th revision (ICD-10) codes: atrial fibrillation (AF), supraventricular tachycardia (SVT), ventricular tachycardia (VT), cardiac arrest (CA), atrioventricular block (AVB), unstable angina (UA), ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), pulmonary embolism (PE), hypertrophic cardiomyopathy (HCM), aortic stenosis (AS), mitral valve prolapse (MVP), mitral valve stenosis (MS), pulmonary hypertension (PHTN), and heart failure (HF). We employed ResNet-based deep learning (DL) using ECG tracings and extreme gradient boosting (XGB) using ECG measurements. When evaluated on the first ECGs per episode of 97,631 holdout patients, the DL models had an area under the receiver operating characteristic curve (AUROC) of <80% for 3 CV conditions (PTE, SVT, UA), 80-90% for 8 CV conditions (CA, NSTEMI, VT, MVP, PHTN, AS, AF, HF) and an AUROC > 90% for 4 diagnoses (AVB, HCM, MS, STEMI). DL models outperformed XGB models with about 5% higher AUROC on average. Overall, ECG-based prediction models demonstrated good-to-excellent prediction performance in diagnosing common CV conditions.

Blood and CSF levels of brain-derived neurotrophic factor in patients with encephalopathy/encephalitis: a systematic review and meta-analysis.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is critical for enhancing the survival and growth of neurons and modulating the synaptic plasticity. BDNF levels have been demonstrated to be changed in plasma and cerebrospinal fluid (CSF) following brain insults such as inflammation or ischemia or infection in several studies. Currently, there is no systematic review regarding BDNF levels in encephalitis or encephalopathy patients. Considering inconsistency between studies, we aimed to pool the data from existing studies to determine whether blood or CSF levels of BDNF are different in patients with encephalopathy/encephalitis. METHODS: We comprehensively searched Web of Science, PubMed, Scopus, and Embase databases to identify eligible studies. The last search occurred in December 2022. RESULTS: 12 studies met our inclusion criteria and ten studies including 283 patients and 323 healthy controls were enrolled in this meta-analysis. In comparison to controls, patients with encephalitis/encephalopathy had higher levels of BDNF in their CSF [standardized mean difference (SMD) = 1.48, 95% CI 0.18-2.77; P = 0.03)], while their blood levels of BDNF did not differ significantly [standardized mean difference (SMD) = 0.27, 95% CI = - 0.71 to 1.25; P = 0.58)]. Moreover, regarding the heterogeneity among studies reporting BDNF blood levels, we performed two subgroup analyses based on the disease etiology and the specimen (plasma and serum); none of them indicated statistically significant difference in BDNF levels between the subgroups (P = 0.41 and 0.20, respectively). CONCLUSION: Meta-analysis provides evidence that patients with encephalopathy/encephalitis have higher CSF levels of BDNF compared to controls.

The analgesic effect and safety of duloxetine in total knee arthroplasty: A systematic review.

Background: Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with clinical efficacy in chronic pain conditions. In this study, we aim to evaluate the analgesic effect and safety of duloxetine in total knee arthroplasty (TKA). Methods: A systematic search was completed on MEDLINE, PsycINFO, and Embase from inception to December 2022 to find relevant articles. We used Cochrane methodology to evaluate the bias of included studies. Investigated outcomes included postoperative pain, opioid consumption, adverse events (AEs), range of motion (ROM), emotional and physical function, patient satisfaction, patient-controlled analgesia (PCA), knee-specific outcomes, wound complications, skin temperature, inflammatory markers, length of stay, and incidence of manipulations. Results: Nine articles involving 942 participants were included in our systematic review. Out of nine papers, eight were randomized clinical trials and one was a retrospective study. The results of these studies indicated the analgesic effect of duloxetine on postoperative pain, which was measured using numeric rating scale and visual analogue scale. Deluxetine was also effective in reducing the morphine requirement and wound complications and enhancing patient satisfaction after surgery. However, the results on ROM, PCA, and knee-specific outcomes were contraventional. Deluxetine was generally safe without serious AEs. The most common AEs included headache, nausea, vomiting, dry mouth, and constipation. Conclusion: Duloxetine may be an effective treatment option for postoperative pain following TKA, but further rigorously designed and well-controlled randomized trials are required.

Towards artificial intelligence-based learning health system for population-level mortality prediction using electrocardiograms.

The feasibility and value of linking electrocardiogram (ECG) data to longitudinal population-level administrative health data to facilitate the development of a learning healthcare system has not been fully explored. We developed ECG-based machine learning models to predict risk of mortality among patients presenting to an emergency department or hospital for any reason. Using the 12-lead ECG traces and measurements from 1,605,268 ECGs from 748,773 healthcare episodes of 244,077 patients (2007-2020) in Alberta, Canada, we developed and validated ResNet-based Deep Learning (DL) and gradient boosting-based XGBoost (XGB) models to predict 30-day, 1-year, and 5-year mortality. The models for 30-day, 1-year, and 5-year mortality were trained on 146,173, 141,072, and 111,020 patients and evaluated on 97,144, 89,379, and 55,650 patients, respectively. In the evaluation cohort, 7.6%, 17.3%, and 32.9% patients died by 30-days, 1-year, and 5-years, respectively. ResNet models based on ECG traces alone had good-to-excellent performance with area under receiver operating characteristic curve (AUROC) of 0.843 (95% CI: 0.838-0.848), 0.812 (0.808-0.816), and 0.798 (0.792-0.803) for 30-day, 1-year and 5-year prediction, respectively; and were superior to XGB models based on ECG measurements with AUROC of 0.782 (0.776-0.789), 0.784 (0.780-0.788), and 0.746 (0.740-0.751). This study demonstrates the validity of ECG-based DL mortality prediction models at the population-level that can be leveraged for prognostication at point of care.

Blood lead level evaluation in children presenting with chronic constipation in Tehran-Iran: a cross-sectional study.

Constipation is a common reason for children seeking medical care worldwide. Abdominal complaints and constipation are also common in lead-poisoned children. This study evaluates the prevalence of abnormal blood lead levels (BLL) among pediatric and adolescent patients and examines the association of constipation with elevated BLL. This was a prospective data collection of patients younger than 18 years old with the chief complaint of constipation seen in the Mofid Children's Hospital gastroenterology clinic and Loghman Hakim pediatric and pediatric gastroenterology clinics were eligible for enrollment in this study. Constipation was defined as infrequent or difficult defecation according to ROME IV criteria lasting 2 months or more. BLL was measured with a fresh capillary whole blood capillary sample. The LeadCare II device assays BLL using an electrochemical technique (anodic stripping voltammetry). A total of 237 patients were enrolled in the study. 122 (51.48%) were female and 115 (48.52%) were male. About one fifth of patients (49; 20.67%) had BLL ≥ 5 µg/dL. The mean BLL in the sample was 3.51 µg/dL. Abdominal pain was the most common symptom accompanying constipation (134; 56%). Multivariate analysis found endoscopic evaluation (P values 0.024, OR 3.646, 95% CI 1.189-11.178), muscle pain (P values 0.020, OR 24.74, 95% CI 1.67-365.83), and maternal education (P values 0.02, OR 4.45, 95% CI 1.27-15.57) with significant differences in groups of patients with normal and elevated BLL. Elevated BLL necessitates an assessment and plans to reduce childhood lead exposure. BLL screening in childhood constipation with refractory chronic abdominal pain may also eradicate the need for invasive procedures like endoscopic evaluation.

Biological, pathological, and multifaceted therapeutic functions of exosomes to target cancer.

Exosomes, small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body. It is considered a "double-edged sword", and depending on its biological source, the action of exosomes varies under physiological conditions. Also, the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome source. Moreover, the uptake of exosomes from the recipients' cells is a vital and initial step for all the physiological actions. There are different mechanisms present in the exosomes' cellular uptake to deliver their cargo to acceptor cells. Once the exosomal uptake takes place, it releases the intracellular particles that leads to activate the physiological response. Even though exosomes have lavish functions, there are some challenges associated with every step of their preparation to bring potential therapeutic efficacy. So, overcoming the pitfalls would give a desired quantity of exosomes with high purity.

Boswellia serrata extract shows cognitive benefits in a double-blind, randomized, placebo-controlled pilot clinical trial in individuals who suffered traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. TBI can result in neuropsychiatric and cognitive problems as well as neurodegenerative pathologies that can appear right after or develop and persist years after injury. METHOD: We conducted a double-blind, randomized, placebo-controlled clinical trial on patients who suffered from TBI three months to three years ago. The patients were randomized to placebo (n = 34) or K-Vie™ group (n = 46) for a treatment period of 3 months. The main primary outcomes include cognitive assessment in the Rey Auditory Verbal Learning Test-Recognition Test (RAVLT), Wechsler adult intelligence Digit Symbol Substitution Test (DSST) and trail-making test part B (TMT-B). Assessments were performed at baseline and at the month 3 follow-up visit. Linear mixed models were carried out to evaluate cognitive changes from baseline across all cognitive assessment tests. RESULT: The current study showed significant (p < 0.05) improvement in cognitive function of patients who were given K-Vie™ compared with placebo across the RAVLT, DSST and TMT-B performance assessments. A larger cohort would be beneficial to further confirm the clinical utility of K-Vie™ and assess its effects in acute phases of TBI.

Post-mortem blood lead analysis; a comparison between LeadCare II and graphite furnace atomic absorption spectrometry analysis results.

PURPOSE: A comparison of the LeadCare II (LCII) point-of-care (POC) device with the gold standard graphite furnace atomic absorption spectroscopy (GFAAS) device was done in the context of post-mortem blood lead concentrations to determine comparability for screening value. METHODS: Consecutive autopsy cases from March 2018 to March 2019 were examined by the forensic medicine center. Blood samples with lead concentrations <10 µg dL-1 by LCII analysis were excluded from GFAAS analysis. Samples were collected from femoral veins or cardiac chambers. Bland-Altman analysis was conducted to evaluate the agreement between both GFAAS and LCII lead values. Linear regression modeling was performed to predict GFAAS results based on LCII results. Five-hundred post-mortem blood samples were evaluated by LCII for blood lead. For 46 cases with LCII blood lead level (BLL) values more than 10 µg dL-1, further analysis was performed by GFAAS. RESULTS: Mean difference of BLL between the two methods was 5.92 µg dL-1 (SD = 7.51; range: -14 to 23.7). GFAAS BLL values were significantly higher than LCII values (p = 0.029). Moreover, substance-user samples had significantly higher GFAAS BLLs (p = 0.006; mean difference = 11.62 µg dL-1). A significant regression equation was found (F [1, 44] = 108.44, p < 0.001, with an R2 of 0.711). Based on Bland-Altman plot averages for both predicted GFAAS BLL and measured GFASS BLL showed a mean difference was 0.014 (SD = 7.51; range: -17.9 to 20). CONCLUSION: In conclusion, on post-mortem BLL samples, LCII and GFAAS show favorable correlation. LCII can be used as a screening technique for post-mortem blood lead analysis.

Adult Lead Poisoning Caused by Contaminated Opium: A Two-Year Longitudinal Follow-Up Study.

Background: A major episode of lead poisoning caused by lead-adulterated opium occurred in Iran in 2016. Patients were removed from exposure and treated with chelating agents. A subset of those patients was evaluated in this follow-up study to evaluate treatment efficacy in relation to patient outcome. Methods: Between March 2016 and December 2017, thirty-five male cases of lead poisoning due to ingestion of lead-adulterated opium were followed for two years. There are three patient groups: 1) those who abstained from opium use; 2) those who continued to use potentially contaminated opium; and 3) those who abstained from opium and were placed on maintenance therapy. Maintenance therapy included: methadone and opium tincture, offered by the Opioid Maintenance Therapy (OMT) clinics. Amongst the three patient groups Blood Lead Levels (BLL), complete blood count, and kidney and liver function tests were compared. Findings: The results of BLL, hemoglobin, hematocrit, and aspartate aminotransferase were significantly different between the admission time and follow-up. Of the three patient groups, no difference was detected in these measures. Conclusions: Treatment of lead poisoning combined with OMT proved an effective method to prevent recurrent lead poisoning.

Environmental assessment of pediatric Lead exposure in Tehran; a prospective cross-sectional study.

BACKGROUND: Ingestion and inhalation are common routes of exposure for lead in humans. Developing countries still have unacceptably high rates of lead toxicity, especially in children. Studies on probable risk factors of lead poisoning in Iranian children are insufficient. In this study, we aimed to evaluate possible environmental factors in children with high blood lead concentrations living in Tehran and neighboring cities. METHODS: In a prospective cross-sectional study between March 2018 and March 2019 we followed all children referred from two pediatric gastrointestinal clinics with blood lead level (BLL) > 5 µg/dL in metropolitan Tehran to investigate possible environmental risk factors in their home. Household specimens including scratched wall paint, house floor dust, windowsill dust, tap water, and consumed spice were evaluated using atomic absorption method to detect lead concentrations. Epidemiological and environmental data collected through in-depth interviews with parents/guardians. Industrial areas were defined based on municipality maps on industrial places. RESULTS: Thirty of 56 parents/guardians with BLL > 5 µg/dL agreed to be followed through environmental investigation. The only categorical statistically significant risk factor was a history of lead poisoning in the family and living in an industrial zone. There was a positive correlation between BLL and interior windowsills dust lead level, r = 0.46, p = 0.01. Scratched paint lead level and BLL showed a significant positive correlation, r = 0.50, p = 0.005. House floor dust lead level (median = 77.4, p < 0.001) and interior windowsill dust lead level (median = 291, p = 0.011) were both significantly higher than the environmental protection agency (EPA) standards of 40 µg/ft2, 250 µg/ft2. Interior windowsill dust lead concentrations were significantly higher in industrial areas (p = 0.026). CONCLUSION: Children's playing environment should be cleaned more often to reduce dust. Moreover, specific rules may need to be implemented for paint lead concentrations and air pollution, especially in industrial areas.

Idiopathic superficial siderosis of the central nervous system.

BACKGROUND: Regardless of the cause of the superficial siderosis (SS) disease, which is bleeding, the source of bleeding cannot be found in some cases. CASE PRESENTATION: In this article, we report two cases with idiopathic SS. Case 1 presented with bilateral hearing loss, cognitive impairment, sleep disturbances, and tremors. Case 2 presented with sensory neural hearing loss, ataxia, and spastic paraparesis. In both cases, brain MRI indicated evidence of SS. CT myelogram and SPECT with labeled RBC couldn't help finding the source of occult bleeding. CONCLUSION: SS is a rare central nervous system disease caused by the deposition of hemosiderin in the brain and spinal cord, which results in the progression of neurological deficits. The cause of this hemorrhage is often subarachnoid haemorrhage, intracranial surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. The condition progresses slowly and, by the time diagnosis is confirmed, the damage is often irreversible. In our cases, brain MRI clarified the definitive diagnosis, but we could not find the source of bleeding. SS should be considered in cases with ataxia and hearing loss, even if no source of bleeding is found.

Chronic neurological diseases and COVID-19: Associations and considerations.

The 2019 novel coronavirus pandemic, severe acute respiratory syndrome CoV-2 (COVID-19), has been a worldwide urgent public health threat, resulting in six-hundred seventy thousand deaths to date. The COVID-19 pandemic has led to a series of public health challenges. One such challenge is the management of diseases such as chronic neurological diseases during an epidemic event. COVID-19 affects all kinds of people, including older people with chronic underlying diseases, who are particularly at risk of severe infection or even death. Chronic neurological diseases such as epilepsy, dementia, Parkinson's disease (PD), and multiple sclerosis (MS) are frequently associated with comorbidities; thus, these patients are in the high-risk category. Therefore, in this article, we review associations and challenges the people with epilepsy, dementia, PD, and MS faces during the COVID-19 pandemic and suggest approaches to provide consensus recommendations on how to provide the best possible care.

Descriptive Epidemiology of Brain and Central Nervous System Tumours: Results from Iran National Cancer Registry, 2010-2014.

BACKGROUND: Central nervous system (CNS) tumours account for only 1-2% of cancer incidence but are a major reason for mortality and morbidity due to malignancies. Recent studies show an increase in the rate of CNS tumours worldwide, especially in developing countries. Moreover, there is significant heterogeneity in epidemiological patterns worldwide. This study is aimed at representing nationwide epidemiology of CNS tumours in Iran. METHODS: Iran National Cancer Registry 2010-2014 data were reviewed for CNS tumours. The epidemiological rates were calculated for both genders and all age groups using the 2011 census information. RESULTS: Out of 17345 cases, 58.5% were men and 41.5% were women. The mean age was 45.55 years ranging from less than 1 month to 100 years old. Average total age-standardized incidence rate (ASR) was 5.19 for primary tumours. The annual percent change (APC) was 14.23% during the study period. The most frequent site and histology recorded were brain, NOS and diffuse astrocytic, respectively. Geographical distribution showed about five-fold difference in ASRs between different provinces. CONCLUSION: The overall ASR calculated was higher than the global rate in 2012 but lower than that of most developed countries, showing an increasing trend which may be due to either advances in diagnosing or risk factor augmentation. The mean age and incident rates were higher than those of previous reports in Iran.

Association of Depression with Migraine without Aura; A Cross-Sectional Study.

OBJECTIVE: Migraine is ranked as the seventh leading cause of disability worldwide, and it is characterized by a manifestation of combined neurological, gastrointestinal, and autonomic symptoms linked with different provoking factors. Aim of the study: This study investigates the association between migraine without aura and depression. METHOD: A total number of 100 patients were enrolled in the study and were divided into two groups: 50 individuals with confirmed migraine without aura (the study group) and 50 individuals with no history of headaches (control group). All individuals were evaluated using the ICHD- II diagnostic criteria for migraine, as well as the Beck test for depression. RESULTS: Statistical analysis showed a significant relationship between migraine without aura and depression (p=0.023), but no significant association between depression and BMI, migraine length, gender, family history of depression, alcoholism, smoking cigarettes and number of drugs consumed. CONCLUSIONS: Based on our data we can confirm an association between depression and migraine without aura.

Positive Effects of Cognitive Behavioral Therapy on Depression, Anxiety and Stress of Family Caregivers of Patients with Prostate Cancer: A Randomized Clinical Trial

Background: The family caregivers of patients with cancer mightexperience various physical, mental, and spiritual difficulties, the neglect of which can causeseriousproblems for theentirefamily. If caregivers are left without appropriate treatment and intervention, their level of physical and mental health will substantially decrease-they will, in other words, become"hidden patients." Materials and Methods: The current study is a clinical trial of 80 family caregivers of patients with prostate cancer, who were allocated to control and experimental groups. The experimental group received 10 sessions of group cognitive behavioral therapy. The 21-item Depression Anxiety Stress Scales were completed before the intervention as well4 and 8 weeks after. Data were analyzed using descriptive statistics (means and standard deviations) andvariousstatistical tests. Results: The results showed thatthecognitivebehavioral intervention reduceddepression, anxiety, and stress among familycaregivers. Conclusion: Because of the positive impact of this intervention, its implementation in clinical care by nurses is recommended.

Neurobehavioral toxicity of carbon nanotubes in mice.

OBJECTIVES: The aim of this study was to evaluate neurobehavioral toxicity of single-walled (SWNTs) and multiwalled carbon nanotubes (MWNTs) in mice. METHODS: Male NMRI mice were randomized into 5 groups ( n = 10 each): Normal control (NC) group was injected intraperitoneally (i.p.) with phosphate-buffered saline (PBS) solution (pH 7.8; ca. 1 mL), MW80 and MW800 groups were injected with either i.p. 80 or 800 mg kg-1 MWNTs suspended in 1 mL of PBS and SW80 and SW800 groups were injected with either i.p. 80 or 800 mg kg-1 SWNTs suspended in 1 mL of PBS. After 2 weeks, five mice from each group were evaluated for brain-derived neurotrophic factor (BDNF) messenger RNA expression and protein content of brain tissues. Locomotion, anxiety, learning and memory, and depression were measured by open field test (OFT), elevated plus-maze (EPM), object recognition test (ORT), and forced swimming test (FST), respectively. RESULTS: Ambulation time and center arena time in the OFT did not change among groups. In the EPM paradigm, SWNTs (800 mg kg-1) and MWNTs (80 and 800 mg kg-1) showed an anxiogenic effect. In ORT, MWNTs (80 mg kg-1) increased the discrimination ratio while in FST, MWNTs showed a depressant effect as compared to vehicle. The BDNF gene expression in mice treated with 80 and 800 mg kg-1 SWNTs or 80 mg kg-1 MWNTs decreased as compared to NC mice although BDNF gene expression increased in mice that were treated with 800 mg kg-1 MWNTs. The whole brain BDNF protein content did not change among groups. CONCLUSION: Our study showed that i.p. exposure to carbon nanotubes (CNTs) may result in behavioral toxicity linked with expression of depression or anxiety that depends on the type of CNTs. In addition, exposure to CNTs changed BDNF gene expression.