Methodological biases in observational hospital studies of COVID-19 treatment effectiveness: pitfalls and potential.

Introduction: This study aims to discuss and assess the impact of three prevalent methodological biases: competing risks, immortal-time bias, and confounding bias in real-world observational studies evaluating treatment effectiveness. We use a demonstrative observational data example of COVID-19 patients to assess the impact of these biases and propose potential solutions. Methods: We describe competing risks, immortal-time bias, and time-fixed confounding bias by evaluating treatment effectiveness in hospitalized patients with COVID-19. For our demonstrative analysis, we use observational data from the registry of patients with COVID-19 who were admitted to the Bellvitge University Hospital in Spain from March 2020 to February 2021 and met our predefined inclusion criteria. We compare estimates of a single-dose, time-dependent treatment with the standard of care. We analyze the treatment effectiveness using common statistical approaches, either by ignoring or only partially accounting for the methodological biases. To address these challenges, we emulate a target trial through the clone-censor-weight approach. Results: Overlooking competing risk bias and employing the naïve Kaplan-Meier estimator led to increased in-hospital death probabilities in patients with COVID-19. Specifically, in the treatment effectiveness analysis, the Kaplan-Meier estimator resulted in an in-hospital mortality of 45.6% for treated patients and 59.0% for untreated patients. In contrast, employing an emulated trial framework with the weighted Aalen-Johansen estimator, we observed that in-hospital death probabilities were reduced to 27.9% in the "X"-treated arm and 40.1% in the non-"X"-treated arm. Immortal-time bias led to an underestimated hazard ratio of treatment. Conclusion: Overlooking competing risks, immortal-time bias, and confounding bias leads to shifted estimates of treatment effects. Applying the naïve Kaplan-Meier method resulted in the most biased results and overestimated probabilities for the primary outcome in analyses of hospital data from COVID-19 patients. This overestimation could mislead clinical decision-making. Both immortal-time bias and confounding bias must be addressed in assessments of treatment effectiveness. The trial emulation framework offers a potential solution to address all three methodological biases.

A new force profile signal for a convex solution of muscle force estimation from electromyographic signals.

High-Density Surface Electromyography (HD-sEMG) is a non-invasive technique for measuring the electrical activity of a muscle with multiple, closely spaced electrodes. Estimation of muscle force is one of the applications of HD-sEMG. Usually, validating different EMG-Force models entails simple movements limited to laboratory settings. The validity of these models in more ecological conditions, requesting force production over a wide frequency band, remains unknown. In this study, we, therefore, compare the results of force prediction using four different types of input force profiles that can be representative of daily life activities, and we investigate whether the crest factor of these different input signals affects force prediction. For predicting the force from sEMG signals, we used our real-time and convex methods. HD-sEMG signals were recorded with 144 channels from the biceps brachii, brachioradialis, and triceps (long, lateral, and medial head) muscles of 24 healthy subjects during random signal, random phase, Schroeder phase, and minimum crest factor (crestmin) signal. The correlation and coefficient of determination (R2) between measured and predicted forces were calculated for the different force feedback profiles. The crestmin signal showed significantly better results based on statistical tests (P-value < 0.05), with correlation and R2 equal to 0.92±0.03 and 0.86±0.05, respectively. The results demonstrate that the crest factor of input signals is a crucial parameter that can impact the performance of EMG-Force models and must be considered during training.Clinical Relevance- This study demonstrates that lower crest factor multisine force profiles result in improved fitness for force prediction and can be used as an alternative to random signals.

Target trial emulation with multi-state model analysis to assess treatment effectiveness using clinical COVID-19 data.

BACKGROUND: Real-world observational data are an important source of evidence on the treatment effectiveness for patients hospitalized with coronavirus disease 2019 (COVID-19). However, observational studies evaluating treatment effectiveness based on longitudinal data are often prone to methodological biases such as immortal time bias, confounding bias, and competing risks. METHODS: For exemplary target trial emulation, we used a cohort of patients hospitalized with COVID-19 (n = 501) in a single centre. We described the methodology for evaluating the effectiveness of a single-dose treatment, emulated a trial using real-world data, and drafted a hypothetical study protocol describing the main components. To avoid immortal time and time-fixed confounding biases, we applied the clone-censor-weight technique. We set a 5-day grace period as a period of time when treatment could be initiated. We used the inverse probability of censoring weights to account for the selection bias introduced by artificial censoring. To estimate the treatment effects, we took the multi-state model approach. We considered a multi-state model with five states. The primary endpoint was defined as clinical severity status, assessed by a 5-point ordinal scale on day 30. Differences between the treatment group and standard of care treatment group were calculated using a proportional odds model and shown as odds ratios. Additionally, the weighted cause-specific hazards and transition probabilities for each treatment arm were presented. RESULTS: Our study demonstrates that trial emulation with a multi-state model analysis is a suitable approach to address observational data limitations, evaluate treatment effects on clinically heterogeneous in-hospital death and discharge alive endpoints, and consider the intermediate state of admission to ICU. The multi-state model analysis allows us to summarize results using stacked probability plots that make it easier to interpret results. CONCLUSIONS: Extending the emulated target trial approach to multi-state model analysis complements treatment effectiveness analysis by gaining information on competing events. Combining two methodologies offers an option to address immortal time bias, confounding bias, and competing risk events. This methodological approach can provide additional insight for decision-making, particularly when data from randomized controlled trials (RCTs) are unavailable.

Population food intake clusters and cardiovascular disease incidence: a Bayesian quantifying of a prospective population-based cohort study in a low and middle-income country.

Aims: This study was designed to explore the relationship between cardiovascular disease incidence and population clusters, which were established based on daily food intake. Methods: The current study examined 5,396 Iranian adults (2,627 males and 2,769 females) aged 35 years and older, who participated in a 10-year longitudinal population-based study that began in 2001. The frequency of food group consumption over the preceding year (daily, weekly, or monthly) was assessed using a 49-item qualitative food frequency questionnaire (FFQ) administered via a face-to-face interview conducted by an expert dietitian. Participants were clustered based on their dietary intake by applying the semi-parametric Bayesian approach of the Dirichlet Process. In this approach, individuals with the same multivariate distribution based on dietary intake were assigned to the same cluster. The association between the extracted population clusters and the incidence of cardiovascular diseases was examined using Cox proportional hazard models. Results: In the 10-year follow-up, 741 participants (401 men and 340 women) were diagnosed with cardiovascular diseases. Individuals were categorized into three primary dietary clusters: healthy, unhealthy, and mixed. After adjusting for potential confounders, subjects in the unhealthy cluster exhibited a higher risk for cardiovascular diseases [Hazard Ratio (HR): 2.059; 95% CI: 1.013, 4.184] compared to those in the healthy cluster. In the unadjusted model, individuals in the mixed cluster demonstrated a higher risk for cardiovascular disease than those in the healthy cluster (HR: 1.515; 95% CI: 1.097, 2.092). However, this association was attenuated after adjusting for potential confounders (HR: 1.145; 95% CI: 0.769, 1.706). Conclusion: The results have shown that individuals within an unhealthy cluster have a risk that is twice as high for the incidence of cardiovascular diseases. However, these associations need to be confirmed through further prospective investigations.

Post-discharge health assessment in survivors of coronavirus disease: a time-point analysis of a prospective cohort study.

PURPOSE:  The objective of this study was to quantitatively evaluate psychological and quality of life-related complications at three months following discharge in hospitalized coronavirus disease 2019 (COVID-19) patients during the pandemic in Iran. METHODS: In this time-point analysis of prospective cohort study data, adult patients hospitalized with symptoms suggestive of COVID-19 were enrolled. Patients were stratified in analyses based on severity. The primary outcomes consisted of psychological problems and pulmonary function tests (PFTs) in the three months following discharge, with Health-related quality of life (HRQoL) as the secondary outcome. Exploratory predictors were determined for both primary and secondary outcomes. RESULTS: 283 out of 900 (30%) eligible patients were accessible for the follow-up assessment and included in the study. The mean age was 53.65 ± 13.43 years, with 68% experiencing a severe disease course. At the time of the final follow-up, participants still reported persistent symptoms, among which fatigue, shortness of breath, and cough were the most common. Based on the regression-adjusted analysis, lower levels of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio was associated with higher levels of depression (standardized ß = - 0.161 (SE = 0.042), P = 0.017) and stress levels (standardized ß =- 0.110 (SE = 0.047), P = 0.015). Furthermore, higher levels of anti-SARS-CoV-2 immunoglobulin-M (IgM) were associated with significantly lower levels of depression (standardized ß = - 0.139 (SE = 0.135), P = 0.031). CONCLUSIONS: There is an association between lung damage during COVID-19 and the reduction of pulmonary function for up to three months from acute infection in hospitalized patients. Varying degrees of anxiety, depression, stress, and low HRQoL frequently occur in patients with COVID-19. More severe lung damage and lower COVID-19 antibodies were associated with lower levels of psychological health.

A real-time and convex model for the estimation of muscle force from surface electromyographic signals in the upper and lower limbs.

Surface electromyography (sEMG) is a signal consisting of different motor unit action potential trains and records from the surface of the muscles. One of the applications of sEMG is the estimation of muscle force. We proposed a new real-time convex and interpretable model for solving the sEMG-force estimation. We validated it on the upper limb during isometric voluntary flexions-extensions at 30%, 50%, and 70% Maximum Voluntary Contraction in five subjects, and lower limbs during standing tasks in thirty-three volunteers, without a history of neuromuscular disorders. Moreover, the performance of the proposed method was statistically compared with that of the state-of-the-art (13 methods, including linear-in-the-parameter models, Artificial Neural Networks and Supported Vector Machines, and non-linear models). The envelope of the sEMG signals was estimated, and the representative envelope of each muscle was used in our analysis. The convex form of an exponential EMG-force model was derived, and each muscle's coefficient was estimated using the Least Square method. The goodness-of-fit indices, the residual signal analysis (bias and Bland-Altman plot), and the running time analysis were provided. For the entire model, 30% of the data was used for estimation, while the remaining 20% and 50% were used for validation and testing, respectively. The average R-square (%) of the proposed method was 96.77 ± 1.67 [94.38, 98.06] for the test sets of the upper limb and 91.08 ± 6.84 [62.22, 96.62] for the lower-limb dataset (MEAN ± SD [min, max]). The proposed method was not significantly different from the recorded force signal (p-value = 0.610); that was not the case for the other tested models. The proposed method significantly outperformed the other methods (adj. p-value < 0.05). The average running time of each 250 ms signal of the training and testing of the proposed method was 25.7 ± 4.0 [22.3, 40.8] and 11.0 ± 2.9 [4.7, 17.8] in microseconds for the entire dataset. The proposed convex model is thus a promising method for estimating the force from the joints of the upper and lower limbs, with applications in load sharing, robotics, rehabilitation, and prosthesis control for the upper and lower limbs.

Target Trial Emulation Using Hospital-Based Observational Data: Demonstration and Application in COVID-19.

Methodological biases are common in observational studies evaluating treatment effectiveness. The objective of this study is to emulate a target trial in a competing risks setting using hospital-based observational data. We extend established methodology accounting for immortal time bias and time-fixed confounding biases to a setting where no survival information beyond hospital discharge is available: a condition common to coronavirus disease 2019 (COVID-19) research data. This exemplary study includes a cohort of 618 hospitalized patients with COVID-19. We describe methodological opportunities and challenges that cannot be overcome applying traditional statistical methods. We demonstrate the practical implementation of this trial emulation approach via clone-censor-weight techniques. We undertake a competing risk analysis, reporting the cause-specific cumulative hazards and cumulative incidence probabilities. Our analysis demonstrates that a target trial emulation framework can be extended to account for competing risks in COVID-19 hospital studies. In our analysis, we avoid immortal time bias, time-fixed confounding bias, and competing risks bias simultaneously. Choosing the length of the grace period is justified from a clinical perspective and has an important advantage in ensuring reliable results. This extended trial emulation with the competing risk analysis enables an unbiased estimation of treatment effects, along with the ability to interpret the effectiveness of treatment on all clinically important outcomes.

Kernel Density Estimation of Electromyographic Signals and Ensemble Learning for Highly Accurate Classification of a Large Set of Hand/Wrist Motions.

The performance of myoelectric control highly depends on the features extracted from surface electromyographic (sEMG) signals. We propose three new sEMG features based on the kernel density estimation. The trimmed mean of density (TMD), the entropy of density, and the trimmed mean absolute value of derivative density were computed for each sEMG channel. These features were tested for the classification of single tasks as well as of two tasks concurrently performed. For single tasks, correlation-based feature selection was used, and the features were then classified using linear discriminant analysis (LDA), non-linear support vector machines, and multi-layer perceptron. The eXtreme gradient boosting (XGBoost) classifier was used for the classification of two movements simultaneously performed. The second and third versions of the Ninapro dataset (conventional control) and Ameri's movement dataset (simultaneous control) were used to test the proposed features. For the Ninapro dataset, the overall accuracy of LDA using the TMD feature was 98.99 ± 1.36% and 92.25 ± 9.48% for able-bodied and amputee subjects, respectively. Using ensemble learning of the three classifiers, the average macro and micro-F-score, macro recall, and precision on the validation sets were 98.23 ± 2.02, 98.32 ± 1.93, 98.32 ± 1.93, and 98.88 ± 1.31%, respectively, for the intact subjects. The movement misclassification percentage was 1.75 ± 1.73 and 3.44 ± 2.23 for the intact subjects and amputees. The proposed features were significantly correlated with the movement classes [Generalized Linear Model (GLM); P-value < 0.05]. An accurate online implementation of the proposed algorithm was also presented. For the simultaneous control, the overall accuracy was 99.71 ± 0.08 and 97.85 ± 0.10 for the XGBoost and LDA classifiers, respectively. The proposed features are thus promising for conventional and simultaneous myoelectric control.

Fetal ECG Extraction From Maternal ECG Using Attention-Based CycleGAN.

A non-invasive fetal electrocardiogram (FECG) is used to monitor the electrical pulse of the fetal heart. Decomposing the FECG signal from the maternal ECG (MECG) is a blind source separation problem, which is hard due to the low amplitude of the FECG, the overlap of R waves, and the potential exposure to noise from different sources. Traditional decomposition techniques, such as adaptive filters, require tuning, alignment, or pre-configuration, such as modeling the noise or desired signal to map the MECG to the FECG. The high correlation between maternal and fetal ECG fragments decreases the performance of convolution layers. Therefore, the masking region of interest based on the attention mechanism was performed to improve the signal generators' precision. The sine activation function was also used to retain more details when converting two signal domains. Three available datasets from the Physionet, including the A&D FECG, NI-FECG, and NI-FECG challenge, and one synthetic dataset using FECGSYN toolbox, were used to evaluate the performance. The proposed method could map an abdominal MECG to a scalp FECG with an average of 98% R-Square [CI 95%: 97%, 99%] as the goodness of fit on the A&D FECG dataset. Moreover, it achieved 99.7% F1-score [CI 95%: 97.8-99.9], 99.6% F1-score [CI 95%: 98.2%, 99.9%] and 99.3% F1-score [CI 95%: 95.3%, 99.9%] for fetal QRS detection on the A&D FECG, NI-FECG and NI-FECG challenge datasets, respectively. Also, the distortion was in the "very good" and "good" ranges. These results are comparable to the state-of-the-art results; thus, the proposed algorithm has the potential to be used for high-performance signal-to-signal conversion.

Systems biology and machine learning approaches identify drug targets in diabetic nephropathy.

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, has become a massive global health burden. Despite considerable efforts, the underlying mechanisms have not yet been comprehensively understood. In this study, a systematic approach was utilized to identify the microRNA signature in DN and to introduce novel drug targets (DTs) in DN. Using microarray profiling followed by qPCR confirmation, 13 and 6 differentially expressed (DE) microRNAs were identified in the kidney cortex and medulla, respectively. The microRNA-target interaction networks for each anatomical compartment were constructed and central nodes were identified. Moreover, enrichment analysis was performed to identify key signaling pathways. To develop a strategy for DT prediction, the human proteome was annotated with 65 biochemical characteristics and 23 network topology parameters. Furthermore, all proteins targeted by at least one FDA-approved drug were identified. Next, mGMDH-AFS, a high-performance machine learning algorithm capable of tolerating massive imbalanced size of the classes, was developed to classify DT and non-DT proteins. The sensitivity, specificity, accuracy, and precision of the proposed method were 90%, 86%, 88%, and 89%, respectively. Moreover, it significantly outperformed the state-of-the-art (P-value ≤ 0.05) and showed very good diagnostic accuracy and high agreement between predicted and observed class labels. The cortex and medulla networks were then analyzed with this validated machine to identify potential DTs. Among the high-rank DT candidates are Egfr, Prkce, clic5, Kit, and Agtr1a which is a current well-known target in DN. In conclusion, a combination of experimental and computational approaches was exploited to provide a holistic insight into the disorder for introducing novel therapeutic targets.

Automatic Classification Between COVID-19 and Non-COVID-19 Pneumonia Using Symptoms, Comorbidities, and Laboratory Findings: The Khorshid COVID Cohort Study.

Coronavirus disease-2019, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was a disaster in 2020. Accurate and early diagnosis of coronavirus disease-2019 (COVID-19) is still essential for health policymaking. Reverse transcriptase-polymerase chain reaction (RT-PCR) has been performed as the operational gold standard for COVID-19 diagnosis. We aimed to design and implement a reliable COVID-19 diagnosis method to provide the risk of infection using demographics, symptoms and signs, blood markers, and family history of diseases to have excellent agreement with the results obtained by the RT-PCR and CT-scan. Our study primarily used sample data from a 1-year hospital-based prospective COVID-19 open-cohort, the Khorshid COVID Cohort (KCC) study. A sample of 634 patients with COVID-19 and 118 patients with pneumonia with similar characteristics whose RT-PCR and chest CT scan were negative (as the control group) (dataset 1) was used to design the system and for internal validation. Two other online datasets, namely, some symptoms (dataset 2) and blood tests (dataset 3), were also analyzed. A combination of one-hot encoding, stability feature selection, over-sampling, and an ensemble classifier was used. Ten-fold stratified cross-validation was performed. In addition to gender and symptom duration, signs and symptoms, blood biomarkers, and comorbidities were selected. Performance indices of the cross-validated confusion matrix for dataset 1 were as follows: sensitivity of 96% [confidence interval, CI, 95%: 94-98], specificity of 95% [90-99], positive predictive value (PPV) of 99% [98-100], negative predictive value (NPV) of 82% [76-89], diagnostic odds ratio (DOR) of 496 [198-1,245], area under the ROC (AUC) of 0.96 [0.94-0.97], Matthews Correlation Coefficient (MCC) of 0.87 [0.85-0.88], accuracy of 96% [94-98], and Cohen's Kappa of 0.86 [0.81-0.91]. The proposed algorithm showed excellent diagnosis accuracy and class-labeling agreement, and fair discriminant power. The AUC on the datasets 2 and 3 was 0.97 [0.96-0.98] and 0.92 [0.91-0.94], respectively. The most important feature was white blood cell count, shortness of breath, and C-reactive protein for datasets 1, 2, and 3, respectively. The proposed algorithm is, thus, a promising COVID-19 diagnosis method, which could be an amendment to simple blood tests and screening of symptoms. However, the RT-PCR and chest CT-scan, performed as the gold standard, are not 100% accurate.

Classification of psychiatric symptoms using deep interaction networks: the CASPIAN-IV study.

Identifying the possible factors of psychiatric symptoms among children can reduce the risk of adverse psychosocial outcomes in adulthood. We designed a classification tool to examine the association between modifiable risk factors and psychiatric symptoms, defined based on the Persian version of the WHO-GSHS questionnaire in a developing country. Ten thousand three hundred fifty students, aged 6-18 years from all Iran provinces, participated in this study. We used feature discretization and encoding, stability selection, and regularized group method of data handling (GMDH) to classify the a priori specific factors (e.g., demographic, sleeping-time, life satisfaction, and birth-weight) to psychiatric symptoms. Self-rated health was the most critical feature. The selected modifiable factors were eating breakfast, screentime, salty snack for depression symptom, physical activity, salty snack for worriedness symptom, (abdominal) obesity, sweetened beverage, and sleep-hour for mild-to-moderate emotional symptoms. The area under the ROC curve of the GMDH was 0.75 (CI 95% 0.73-0.76) for the analyzed psychiatric symptoms using threefold cross-validation. It significantly outperformed the state-of-the-art (adjusted p < 0.05; McNemar's test). In this study, the association of psychiatric risk factors and the importance of modifiable nutrition and lifestyle factors were emphasized. However, as a cross-sectional study, no causality can be inferred.

Absolute mortality risk assessment of COVID-19 patients: the Khorshid COVID Cohort (KCC) study.

BACKGROUND: Already at hospital admission, clinicians require simple tools to identify hospitalized COVID-19 patients at high risk of mortality. Such tools can significantly improve resource allocation and patient management within hospitals. From the statistical point of view, extended time-to-event models are required to account for competing risks (discharge from hospital) and censoring so that active cases can also contribute to the analysis. METHODS: We used the hospital-based open Khorshid COVID Cohort (KCC) study with 630 COVID-19 patients from Isfahan, Iran. Competing risk methods are used to develop a death risk chart based on the following variables, which can simply be measured at hospital admission: sex, age, hypertension, oxygen saturation, and Charlson Comorbidity Index. The area under the receiver operator curve was used to assess accuracy concerning discrimination between patients discharged alive and dead. RESULTS: Cause-specific hazard regression models show that these baseline variables are associated with both death, and discharge hazards. The risk chart reflects the combined results of the two cause-specific hazard regression models. The proposed risk assessment method had a very good accuracy (AUC = 0.872 [CI 95%: 0.835-0.910]). CONCLUSIONS: This study aims to improve and validate a personalized mortality risk calculator based on hospitalized COVID-19 patients. The risk assessment of patient mortality provides physicians with additional guidance for making tough decisions.

A Comprehensive Review of Computer-Aided Diagnosis of Major Mental and Neurological Disorders and Suicide: A Biostatistical Perspective on Data Mining.

The World Health Organization (WHO) suggests that mental disorders, neurological disorders, and suicide are growing causes of morbidity. Depressive disorders, schizophrenia, bipolar disorder, Alzheimer's disease, and other dementias account for 1.84%, 0.60%, 0.33%, and 1.00% of total Disability Adjusted Life Years (DALYs). Furthermore, suicide, the 15th leading cause of death worldwide, could be linked to mental disorders. More than 68 computer-aided diagnosis (CAD) methods published in peer-reviewed journals from 2016 to 2021 were analyzed, among which 75% were published in the year 2018 or later. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was adopted to select the relevant studies. In addition to the gold standard, the sample size, neuroimaging techniques or biomarkers, validation frameworks, the classifiers, and the performance indices were analyzed. We further discussed how various performance indices are essential based on the biostatistical and data mining perspective. Moreover, critical information related to the Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines was analyzed. We discussed how balancing the dataset and not using external validation could hinder the generalization of the CAD methods. We provided the list of the critical issues to consider in such studies.

High-density surface electromyography signals during isometric contractions of elbow muscles of healthy humans.

This paper presents a dataset of high-density surface EMG signals (HD-sEMG) designed to study patterns of sEMG spatial distribution over upper limb muscles during voluntary isometric contractions. Twelve healthy subjects performed four different isometric tasks at different effort levels associated with movements of the forearm. Three 2-D electrode arrays were used for recording the myoelectric activity from five upper limb muscles: biceps brachii, triceps brachii, anconeus, brachioradialis, and pronator teres. Technical validation comprised a signals quality assessment from outlier detection algorithms based on supervised and non-supervised classification methods. About 6% of the total number of signals were identified as "bad" channels demonstrating the high quality of the recordings. In addition, spatial and intensity features of HD-sEMG maps for identification of effort type and level, have been formulated in the framework of this database, demonstrating better performance than the traditional time-domain features. The presented database can be used for pattern recognition and MUAP identification among other uses.

A one-year hospital-based prospective COVID-19 open-cohort in the Eastern Mediterranean region: The Khorshid COVID Cohort (KCC) study.

The COVID-19 is rapidly scattering worldwide, and the number of cases in the Eastern Mediterranean Region is rising. Thus, there is a need for immediate targeted actions. We designed a longitudinal study in a hot outbreak zone to analyze the serial findings between infected patients for detecting temporal changes from February 2020. In a hospital-based open-cohort study, patients are followed from admission until one year from their discharge (the 1st, 4th, 12th weeks, and the first year). The patient recruitment phase finished at the end of August 2020, and the follow-up continues by the end of August 2021. The measurements included demographic, socio-economics, symptoms, health service diagnosis and treatment, contact history, and psychological variables. The signs improvement, death, length of stay in hospital were considered primary, and impaired pulmonary function and psychotic disorders were considered main secondary outcomes. Moreover, clinical symptoms and respiratory functions are being determined in such follow-ups. Among the first 600 COVID-19 cases, 490 patients with complete information (39% female; the average age of 57±15 years) were analyzed. Seven percent of these patients died. The three main leading causes of admission were: fever (77%), dry cough (73%), and fatigue (69%). The most prevalent comorbidities between COVID-19 patients were hypertension (35%), diabetes (28%), and ischemic heart disease (14%). The percentage of primary composite endpoints (PCEP), defined as death, the use of mechanical ventilation, or admission to an intensive care unit was 18%. The Cox Proportional-Hazards Model for PCEP indicated the following significant risk factors: Oxygen saturation < 80% (HR = 6.3; [CI 95%: 2.5,15.5]), lymphopenia (HR = 3.5; [CI 95%: 2.2,5.5]), Oxygen saturation 80%-90% (HR = 2.5; [CI 95%: 1.1,5.8]), and thrombocytopenia (HR = 1.6; [CI 95%: 1.1,2.5]). This long-term prospective Cohort may support healthcare professionals in the management of resources following this pandemic.

A Hybrid Dynamic Wavelet-Based Modeling Method for Blood Glucose Concentration Prediction in Type 1 Diabetes.

BACKGROUND: Diabetes mellitus (DM) is a chronic disease that affects public health. The prediction of blood glucose concentration (BGC) is essential to improve the therapy of type 1 DM (T1DM). METHODS: Having considered the risk of hyper- and hypo-glycemia, we provide a new hybrid modeling approach for BGC prediction based on a dynamic wavelet neural network (WNN) model, including a heuristic input selection. The proposed models include a hybrid dynamic WNN (HDWNN) and a hybrid dynamic fuzzy WNN (HDFWNN). These wavelet-based networks are designed based on dominant wavelets selected by the genetic algorithm-orthogonal least square method. Furthermore, the HDFWNN model structure is improved using fuzzy rule induction, an important innovation in the fuzzy wavelet modeling. The proposed networks are tested on real data from 12 T1DM patients and also simulated data from 33 virtual patients with an UVa/ Padova simulator, an approved simulator by the US Food and Drug Administration. RESULTS: A comparison study is performed in terms of new glucose-based assessment metrics, such as gFIT, glucose-weighted form of ESODn (gESODn), and glucose-weighted R2 (gR2). For real patients' data, the values of the mentioned indices are accomplished as gFIT = 0.97 ± 0.01, gESODn = 1.18 ± 0.38, and gR2 = 0.88 ± 0.07. HDFWNN, HDWNN and jump NN method showed the prediction error (root mean square error [RMSE]) of 11.23 ± 2.77 mg/dl, 10.79 ± 3.86 mg/dl and 16.45 ± 4.33 mg/dl, respectively. CONCLUSION: Furthermore, the generalized estimating equation and post hoc tests show that proposed models perform better compared with other proposed methods.

Pathways leading to prevention of fatal and non-fatal cardiovascular disease: An interaction model on 15 years population-based cohort study.

BACKGROUND: A comprehensive study on the interaction of cardiovascular disease (CVD) risk factors is critical to prevent cardiovascular events. The main focus of this study is thus to understand direct and indirect relationships between different CVD risk factors. METHODS: A longitudinal data on adults aged ≥35 years, who were free of CVD at baseline, were used in this study. The endpoints were CVD events, whereas their measurements were demographic, lifestyle components, socio-economics, anthropometric measures, laboratory findings, quality of life status, and psychological factors. A Bayesian structural equation modelling was used to determine the relationships among 21 relevant factors associated with total CVD, stroke, acute coronary syndrome (ACS), and fatal CVDs. RESULTS: In this study, a total of 3161 individuals with complete information were involved in the study. A total of 407 CVD events, with an average age of 54.77(10.66) years, occurred during follow-up. The causal associations between six latent variables were identified in the causal network for fatal and non-fatal CVDs. Lipid profile, with the coefficient of 0.26 (0.01), influenced the occurrence of CVD events as the most critical factor, while it was indirectly mediated through risky behaviours and comorbidities. Lipid profile at baseline was influenced by a wide range of other protective factors, such as quality of life and healthy lifestyle components. CONCLUSIONS: Analysing a causal network of risk factors revealed the flow of information in direct and indirect paths. It also determined predictors and demonstrated the utility of integrating multi-factor data in a complex framework to identify novel preventable pathways to reduce the risk of CVDs.

COVID-SAFE: An IoT-Based System for Automated Health Monitoring and Surveillance in Post-Pandemic Life.

In the early months of the COVID-19 pandemic with no designated cure or vaccine, the only way to break the infection chain is self-isolation and maintaining the physical distancing. In this article, we present a potential application of the Internet of Things (IoT) in healthcare and physical distance monitoring for pandemic situations. The proposed framework consists of three parts: a lightweight and low-cost IoT node, a smartphone application (app), and fog-based Machine Learning (ML) tools for data analysis and diagnosis. The IoT node tracks health parameters, including body temperature, cough rate, respiratory rate, and blood oxygen saturation, then updates the smartphone app to display the user health conditions. The app notifies the user to maintain a physical distance of 2 m (or 6 ft), which is a key factor in controlling virus spread. In addition, a Fuzzy Mamdani system (running at the fog server) considers the environmental risk and user health conditions to predict the risk of spreading infection in real time. The environmental risk conveys from the virtual zone concept and provides updated information for different places. Two scenarios are considered for the communication between the IoT node and fog server, 4G/5G/WiFi, or LoRa, which can be selected based on environmental constraints. The required energy usage and bandwidth (BW) are compared for various event scenarios. The COVID-SAFE framework can assist in minimizing the coronavirus exposure risk.