Managing Risk to Improve Health Outcomes: How to Move Population Health Forward in an Era of Uncertainty

Abstracts 2020

Forecasting of COVID-19 infections in E7 countries and proposing some policies based on the Stringency Index

COVID-19 infection data of Emerging 7 (E7) countries, namely Brazil, China, India, Indonesia, Mexico, Russia, and Turkey were described by an empirical model or a special case of this empirical model. Near-future forecasts were also performed. Moreover, the causalities between the Stringency Index’s indicators and total cases in E7 countries in COVID-19 period were examined. Countries were grouped as “stationary,” “transition,” and “exponential” based on the data and model fits. The proposed models produced good fits to the COVID-19 data of E7 countries and it was possible to predict the number of cases in the near future. Some policies to control total cases in E7 countries were also proposed in the final phase of this study based on the findings and forecasting in these countries.

The use of lung ultrasound during the COVID-19 pandemic

The novel coronavirus disease (COVID-19) is a challenge to every health system. Unfortunately, it is unlikely that this pandemic will disappear soon. No health system, with its present resources and workflow, is capable enough to deal with a full-blown wave of this pandemic. Acquisition of specific new skills may be fundamental in delivering appropriate health care for our patients. The gold standard for diagnosis of the COVID-19 infection is real-time reverse transcription polymerase chain reaction. Radiological investigations (chest X-ray or high-resolution computerized tomography [CT]) can be helpful both for diagnosis and management, but they have many limitations. Ultrasound has been suggested as a reliable and accurate tool for assessing the lungs in COVID-19 patients. Lung ultrasound (LUS) can show specific signs of inter-stitial pneumonia, which is characteristic of COVID-19 pulmonary infection. In addition, nonradiologist specialists with experience in ultrasound can be trained on LUS with a relatively rapid learning curve. In pregnancy, LUS can be particularly useful due to the avoidance of exposure to ionizing radiation. In this review, we present the advantages, techniques, and limitations of the use of LUS during the COVID-19 pandemic, with specific focus on pregnancy.

New-generation antiepileptic drugs during pregnancy and the risk of attention-deficit hyperactivity disorder

The use of maternal antiepileptic drug (AED) during pregnancy is associated with an increased risk of cognitive adverse effects among the offspring. As new-generation AEDs continue to enter the market, evidence on their safety during pregnancy is limited yet necessary. To date, there are no published reviews summarizing the evidence of new-generation AED exposure in utero and the development of attention deficit-hyperactivity disorder (ADHD) in the offspring. The objective of this scoping review is to summa-rize the available evidence on the risk of ADHD after maternal exposure to new-generation AEDs during pregnancy. We searched EMBASE and MEDLINE for articles published from January 1988 to April 2020. New-generation AEDs were considered if marketed after 1988. ADHD was defined as attention-deficit hyperac-tivity disorder, hyperkinetic disorder, hyperkinesis, or conduct disorder. Of the total articles screened (n = 805), eight publications were finally included (seven cohort studies and one systematic review). Across the studies, the sample size of pregnant women exposed to AEDs ranged from 1 to 1383. Monotherapy was examined in six studies (mostly lamotrigine), while only two studies examined polytherapy. The included studies reported a range of adjusted relative risks, from 0.84 [0.59– 1.19] to 1.63 [0.41–6.06]. Lamotrigine monotherapy holds the largest body of evidence, concluding that no significant risk of ADHD exists among the offspring. However, the available evidence is considered scarce and has several method-ological limitations. Disentangling the effect of AEDs from epilepsy itself and examining polytherapies are challenges that merit additional investigations. Further comparative safety studies with longer follow-up periods and large sample sizes are needed to accurately quantify the true impact of new-generation AED exposure during pregnancy and ADHD in children.

The Role of Vegan Diets in Lipotoxicity-Induced Beta-Cell Dysfunction in Type-2-Diabetes

Type-2-diabetes is considered the new plague of the current century and both, its incidence and prevalence are rapidly increasing. Chronic insulin resistance and a progressive decline in beta-cell function are discussed as the root causes of type-2-diabetes. Both were associated with obesity and pathologically elevated concentrations of circulating free fatty acids in the blood. The harmful effects of chronically elevated free fatty acid levels on glucose homeostasis and non-adipose tissues are referred to as lipotoxicity. Pancreatic beta-cells appear to be particularly vulnerable and both, dietary fat quantity and quality may impact beta-cell function. Diets high in saturated fats are especially harmful to beta-cells while (poly-)unsaturated fatty acids were associated with beta-cell protective effects. This review examined how a dietary modification towards a low-fat vegan diet, which is particularly low in saturated and trans-fats, could help to prevent or reduce lipotoxicity-induced beta cell dysfunction. Several potential mechanisms of action were identified including: (1) reduced total fat intake (fat quantity), (2) a more favorable polyunsaturated fatty acid to saturated fatty acid ratio (fat quality), (3) improved body weight and a reduction in adipose tissue mass, and finally (4) improved glycemic control. The latter appears of paramount importance in light of the accumulating evidence that lipotoxic events are tightly coupled to excess glucose levels. All four mechanisms are likely to contribute complementarily to improved beta-cell function in individuals with type-2-diabetes and may reduce the likelihood of lipotoxic events to occur. Physicians must consider these findings when counseling patients on lifestyle and nutrition.

Experimental evidence on the efficacy of two new metabolic modulators on mitochondrial biogenesis and function in mouse cardiomyocytes

Proper maintenance of mitochondrial homeostasis is essential for cell health, and mitochondrial dysfunction underlies several metabolic and heart diseases. Stimulation of mitochondrial biogenesis represents a valuable therapeutic tool for the prevention and treatment of disorders characterized by a deficit in energy metabolism. The present study aimed to potentiate the mitochondrial biogenetic efficacy of an amino acid (AA) mixture, enriched in branched-chain amino acids (BCAAs), which we previously showed to boost mitochondrial biogenesis, leading to life span extension and reducing of muscle and liver damage. Hence, we designed and studied several innovative mixtures. Here, we report on two new AA formulas, α5 and E7, created on the BCAA-enriched amino acid mixture (BCAAem) template and enriched with Krebs cycle substrates, including succinate, malate, and citrate. Cardiomyocytes in culture exposed to either mixture showed increased mitochondrial DNA amount, mitochondrial biogenesis markers, and oxygen consump-tion. Furthermore, α5 and E7 also increased the expression of BCAA catabolic genes. Most importantly, all of these effects of α5 and E7 were more pronounced than those observed with BCAAem, confirming the higher mitochondrial biogenesis potential of these new formulas. Therefore, α5 and E7 could represent a more efficient tool for the nutritional treatment of diseases in which energy production is defective.

Metabolic abnormalities among HIV-infected patients: The rational of national health security for people living with HIV

In the era of highly active antiretroviral therapy (ART), traditional risk factors for metabolic syndrome are presented as increasing age. In low- and middle-income countries, the restricted benefit package of national health security for human immunodeficiency virus (HIV) does not facilitate the early detection of metabolic disorders. In order to assess the rational of national health security for metabolic abnormalities among people living with HIV (PLHIV), this retrospective study aims to determine the occurrence of metabolic abnormalities and its predicting factors. The study was approved by the hospital ethics committee and conducted at the internal medicine clinic, Pathum Thani Hospital, Thailand. Patients with HIV having had at least 1 year of first-line ART, and having their fasting glucose, fasting lipid profile, and blood pressure assessed before ART were recruited into the study. Those with any abnormal metabolic component prior to ART or absent history of ART were excluded. The metabolic abnormalities were defined as any of the following: elevated triglyceride, reduced high-density lipoprotein (HDL), elevated blood pressure, elevated fasting glucose, or on drug treatment for these metabolic abnormalities. The occurrence of metabolic abnormalities was found in 102 of 340 patients (30.0%). Hypertension (11.4%) was the most common abnormality. Age became the single predictor of metabolic abnormalities (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.00–1.06). Aging patients with HIV should be the target group for monitoring and treating metabolic abnormalities. The revision of the benefit package on metabolic abnormalities is urgently needed to promote a better quality of life.

An application of a mixture of exponential distributions for assessing hazard rates from COVID-19

In the present study, we are interested in modeling repose time periods (the length of the time intervals between successive deaths) caused by a new, widespread disease called covid-19. This is useful for predicting probabilities of new deaths that occur within pre-determined time intervals. In practical applications, the choice of the statistical model is crucial for obtaining accurate estimates of death hazard rates. Based on an earlier research, we propose to use a mixture of exponential distributions; this model is simple to implement when hazard rates obtained from the components of the mixture are easily calculated, and it is adequate for dealing with nonstationary time series as those appearing in the case of this disease. The model is then applied to the example of Italy, and it appears to be also useful for comparing hazard rates along time.

Statin Initiation: Guideline Concordance and Characteristics of New Users in Quebec, Canada

Statins are widely prescribed for the prevention of cardiovascular (CV) events. Our objective was to describe the characteristics of patients newly prescribed a statin by general practitioners and assess the concordance of prescribing with national guidelines. Patients who were 18 years or older, French-speaking, available for the 2-year study duration, and had no history of statin use were recruited. Biological parameters were measured, and medical history, sociodemographic characteristics, and health behaviours were recorded using structured questionnaires. Patients’ eligibility for a statin was assessed using the Canadian Cardiovascular Society’s dyslipidemia guidelines. Of the 1631 new statin-users enrolled, 47.6% were women. The mean age for all patients was 57.4 years. According to the Canadian guidelines, 50.6% of patients were considered at high risk for a CV event or had a statin-indicated condition. Moderate and low-risk patients represented 26.7 and 22.7% of patients, respectively.

Ten years of evidence for the diagnostic assessment of preschoolers with prenatal alcohol exposure

The assessment of preschoolers with prenatal alcohol exposure (PAE) is challenging for many diagnostic teams and clinicians. The 2016 Canadian Fetal Alcohol Spectrum Disorder (FASD) diagnostic guidelines describe the assessments recommended for individuals with PAE in various age groups. Interpretation of brain domains constituting global impairment in preschoolers is not well described in the literature, and there has been clinical reluctance to consider the interpretation of clinical assessments as definitively diagnostic in this age group. This study describes the results of 10-year retrospective clinical data of over 300 preschoolers with PAE referred to the Manitoba FASD Centre for assessment of FASD. Preschoolers who met the criteria for a diagnosis of FASD showed significantly greater global developmental impairment, compared with those with PAE alone. They also demonstrated poorer receptive and expressive language abilities when compared with preschoolers who were not diagnosed. Preschoolers with FASD were rated as having more difficulties with executive functioning skills and adaptive functioning skills, compared to their counterparts. Significant deficits were found in fine-motor, visual-motor, and components of gross-motor skills. Importantly, significant sensory processing differences are particularly evident in preschoolers and are important in understanding behavior and in intervention planning. Together, standardized assessment of motor and sensory processing skills, with a comprehensive assessment of language, are significant predictors of FASD diagnosis for preschoolers with PAE.