The Atrial FibriLlatiOn (FLOW-AF) Registry in the Middle East and North Africa: Patient Characteristics, Treatment Patterns and Outcomes.

INTRODUCTION: Limited data on atrial fibrillation (AF) are available from the Middle East and North Africa region (MENA). The aim of the FLOW-AF registry was to evaluate the characteristics, treatment patterns, and clinical and economic outcomes of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) in MENA. METHODS: This multi-center, prospective, observational study (the FLOW-AF registry) enrolled patients newly diagnosed with NVAF across Egypt, Lebanon, Kingdom of Saudi Arabia, and United Arab Emirates. The data collection occurred at enrollment (baseline) and after 6- and 12-months (follow-up). Baseline data included demographics, AF characteristics, medical history, and anti-thrombotic treatment patterns. Clinical events, healthcare resource utilization, and direct costs were collected at follow-up. RESULTS: The study enrolled a total of 1418 patients (52.7% males and 47.3% females). The mean age of the patients was 64.5 years and 90.6% were white. The mean (standard deviation) CHA2DS2-VASc and HAS-BLED risk scores were 2.7 (1.6) and 1.6 (1.2), respectively. Non-vitamin K antagonist oral anticoagulants, antiplatelet therapy, and vitamin K antagonists were prescribed to 65.8%, 16.4%, and 12.9% patients, respectively. During follow-up, the following rates of clinical outcomes were observed: bleeding events (1.7%), transient ischemic attack (1.7%), all-cause mortality (1.7%), stroke (0.6%), myocardial infarction (0.2%), and systemic embolism (0.08%). CONCLUSIONS: This MENA patient population was younger and had lower mean baseline CHA2DS2-VASc and HAS-BLED scores. The rates of clinical outcomes over 1-year in this study were low. Longer follow-up is required to comprehensively assess clinical outcomes in this patient population.

Prevalence of infections and antimicrobial use in the acute-care hospital setting in the Middle East: Results from the first point-prevalence survey in the region.

OBJECTIVES: Community-acquired (CAIs) and healthcare-associated (HAIs) infections are associated with significant morbidity and mortality. Data related to the epidemiology of these infections in the Middle East is scarce. The aim of this study is to estimate the prevalence of infections and antimicrobial use in the acute hospital setting in this region. METHODS: A multicentre Point-Prevalence Survey was conducted in seven Middle Eastern countries: Egypt, Kingdom of Saudi Arabia, United Arab Emirates, Lebanon, Oman, Kuwait and Bahrain. Data were collected by the infection control and infectious diseases teams of the respective hospitals. Study surveys were completed in one day (03 April 2018). RESULTS: The overall point prevalence of infection was 28.3%; HAI and CAI point prevalence was 11.2% and 16.8%, respectively. The majority of patients with an infection (98.2%) were receiving antimicrobial therapy. There were high levels of resistance to antimicrobials among Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae and other Klebsiella sp. CONCLUSIONS: Our findings indicate that the point prevalence of both HAI and CAI is high in a sample of Middle Eastern countries. These findings along with the increased use of antimicrobials represent a significant public health problem in the region; particularly in light of the growing regional antimicrobial resistance.

Rituximab utilization for approved and off-label nononcology indications and patients' experiences with the Patient Alert Card.

This study used retrospective chart review and survey data to evaluate: (1) off-label use of rituximab (MabThera®/Rituxan®) in autoimmune conditions and (2) patients' receipt and knowledge of the Patient Alert Card (PAC), a risk minimization measure for progressive multifocal leukoencephalopathy (PML) and serious infections. Anonymized patient data were collected from infusion centers in Europe from December 2015 to July 2017. Adults receiving rituximab in the same centers were provided a self-administered survey. Outcomes included patterns of off-label rituximab use for nononcology indications, and evaluation of patients' receipt and knowledge of the PAC and its impact. Of 1012 patients in the retrospective chart review, 70.2% received rituximab for rheumatoid arthritis or granulomatosis with polyangiitis/microscopic polyangiitis, and 29.8% received rituximab off label. Among 524 survey participants, 32.8% reported receiving the PAC, 59.3% reported not receiving the PAC and 7.9% did not know whether they received the PAC. A total of 72.4% of patients reported that they were unaware that some patients receiving rituximab experience PML. A higher proportion of PAC recipients identified PML as a potential risk of rituximab than nonrecipients (37.8% vs 19.9%); 58.3% of PAC recipients had poor awareness of PML. Most PAC recipients (90.0%) and nonrecipients (85.5%) correctly answered that they should seek medical attention for infection symptoms. In conclusion, approximately 30% of patients received off-label rituximab. Most patients reported not receiving the PAC or having knowledge of PML but demonstrated understanding of the recommended action in the event of infection symptoms, regardless of PAC receipt.

Childhood attention-deficit/hyperactivity disorder symptoms are risk factors for obesity and physical inactivity in adolescence.

OBJECTIVE: To prospectively investigate the association and directionality between attention-deficit/hyperactivity disorder (ADHD) symptoms and obesity from childhood to adolescence in the general population. We examined whether obesogenic behaviors, namely, physical inactivity and binge eating, underlie the potential ADHD symptom-obesity association. We explored whether childhood conduct disorder (CD) symptoms are related to adolescent obesity/physical inactivity. METHOD: At 7 to 8 years (n = 8,106), teachers reported ADHD and CD symptoms, and parents reported body mass index (BMI) and physically active play. At 16 years (n = 6,934), parents reported ADHD symptoms; adolescents reported physical activity (transformed to metabolic equivalent of task [MET] hours per week) and binge eating; BMI and waist-hip ratio (WHR) were measured via clinical examination. Obesity was defined using the International Obesity Task Force (IOTF) cut-offs for BMI and the 95th percentile cut-off for WHR. RESULTS: Childhood ADHD symptoms significantly predicted adolescent obesity, rather than the opposite. Inattention-hyperactivity symptoms at 8 years were associated with indices of obesity at 16 years (obese BMI: odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.10-3.33; 95th percentile WHR: OR = 1.71, 95% CI = 1.05-2.78), adjusted for gender, baseline BMI, physical activity, family structure change, and maternal education. Child CD symptoms associated with indices of adolescent obesity. Reduced physically active play in childhood predicted adolescent inattention (OR = 1.61, 95% CI = 1.16-2.24). Childhood ADHD and CD symptoms were linked with physical inactivity in adolescence (inattention-hyperactivity; OR = 1.60, 95% CI = 1.20-2.13), but not binge eating. Physical inactivity mediated the associations. CONCLUSIONS: Children with ADHD or CD symptoms are at increased risk for becoming obese and physically inactive adolescents. Physical activity may be beneficial for both behavior problems and obesity.

Prenatal glucocorticoid treatment and later mental health in children and adolescents.

BACKGROUND: Animal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans. METHODS: Using propensity-score-matching, children prenatally exposed to synthetic glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important confounders related to sGC treatment--gestational age and pre-pregnancy BMI. We also used mixed-effects modeling to analyse the entire cohort--matching each sGC case, n=37, to all possible controls, n=6079, on gestational age and sex. We obtained data from the Northern Finland Birth Cohort 1986 at four waves--pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from medical records. Mental health was assessed at 8 years by teachers with the Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self-Report (YSR) scale. RESULTS: Prenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Using the propensity-score-matched subsample, linear multiple regression showed prenatal sGC was significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23-16.45]) and inattention (B= .97 [95% CI: .16-1.80]) at 8 years after control for relevant confounders. Similar findings were obtained at 16 years, but did not reach statistical significance. Mediation by birthweight/placental weight was not detected. CONCLUSIONS: This study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain.

Placental size is associated with mental health in children and adolescents.

BACKGROUND: The role of the placenta in fetal programming has been recognized as a highly significant, yet often neglected area of study. We investigated placental size in relation to psychopathology, in particular attention deficit hyperactivity disorder (ADHD) symptoms, in children at 8 years of age, and later as adolescents at 16 years. METHODOLOGY/PRINCIPAL FINDINGS: Prospective data were obtained from The Northern Finland Birth Cohort (NFBC) 1986. Placental weight, surface area and birth weight were measured according to standard procedures, within 30 minutes after birth. ADHD symptoms, probable psychiatric disturbance, antisocial disorder and neurotic disorder were assessed at 8 years (n = 8101), and ADHD symptoms were assessed again at 16 years (n = 6607), by teachers and parents respectively. We used logistic regression analyses to investigate the association between placental size and mental health outcomes, and controlled for gestational age, birth weight, socio-demographic factors and medical factors, during gestation. There were significant positive associations between placental size (weight, surface area and placental-to-birth-weight ratio) and mental health problems in boys at 8 and 16 years of age. Increased placental weight was linked with overall probable psychiatric disturbance (at 8 y, OR= 1.14 [95% CI= 1.04-1.25]), antisocial behavior (at 8 y, OR = 1.14 [95% CI= 1.03-1.27]) and ADHD symptoms (inattention-hyperactivity at 16 y, OR= 1.19 [95% CI = 1.02-1.38]). No significant associations were detected among girls. CONCLUSIONS/SIGNIFICANCE: Compensatory placental growth may occur in response to prenatal insults. Such overgrowth may affect fetal development, including brain development, and ultimately contribute to psychopathology.

Maternal prenatal anxiety and downregulation of placental 11ß-HSD2.

BACKGROUND: Raised maternal anxiety during pregnancy is associated with increased risk of adverse neurodevelopmental outcomes for her child. The mechanisms underlying this are not known but animal studies suggest prenatal stress may alter the function of the placenta. Here we determined whether maternal prenatal anxiety was associated with a downregulation of placental 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), the enzyme which metabolises cortisol. METHODS: We recruited mothers the day before delivery by elective caesarean, and gave them the Spielberger Trait and State anxiety and Edinburgh Depression self-rating scales. Placentae were collected and aliquots stored for later analysis. RESULTS: Prenatal Trait anxiety was negatively correlated with placental 11ß-HSD2 mRNA expression (r=-0.40, p<0.01, n=56). Results were similar with male and female fetuses (r=-0.39, p=0.04, n=28; r=-0.40, p=0.03, n=28) respectively. Results were also significant with State anxiety (r=-0.27, p=0.05, n=56) but somewhat weaker for depression (r=-0.20, p=0.13, n=56). Preliminary analyses on a subset of cases (n=25) suggested parallel results for enzyme activity. CONCLUSIONS: These findings provide evidence for an association between prenatal maternal mood and downregulation of placental 11ß-HSD2. Results are consistent with raised maternal anxiety being associated with increased fetal exposure to maternal cortisol, and support the hypothesis that this may be one mechanism underlying fetal programming by prenatal stress.