Isolated epileptiform activity in children and adolescents: prevalence, relevance, and implications for treatment.

In the field of psychiatry diagnoses are primarily based on the report of symptoms from either the patient, parents, or both, and a psychiatrist's observations. A psychiatric diagnosis is currently the most widely used basis for medication selection and the brain is seldom investigated directly as a source of those symptoms. This study addresses the request from the National Institute of Mental Health (NIMH) Research Domain Criteria Project (RDoC) for scientific research into neurological abnormalities that can be linked to psychiatric symptoms for the purpose of predicting medication response. One such neurological abnormality that has been the focus of many studies over the last three decades is isolated epileptiform discharges (IEDs) in children and adolescents without seizures. We conducted a systematic review of the literature to determine prevalence rates of IEDs within diagnostic categories. We then compared the prevalence of IEDs in the selected literature to our IRB-approved data archive. Our study found a consistent high prevalence of IEDs specifically for ADHD (majority > 25%) and ASD (majority > 59%), and consistent low prevalence rates were found for Depression (3%). If children and adolescents have failed multiple medication attempts, and more than one-third of them have IEDs, then an EEG would be justified within the RDoC paradigm.

Drug-drug interactions between triazole antifungal agents used to treat invasive aspergillosis and immunosuppressants metabolized by cytochrome P450 3A4.

Patients undergoing treatment with immunosuppressant drugs following solid organ or hematopoietic stem cell transplantation are at particular risk for development of serious infections such as invasive aspergillosis. Four triazole antifungal drugs, voriconazole, posaconazole, itraconazole, and isavuconazole, are approved to treat invasive aspergillosis either as first- or second-line therapy. All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus. Thus, co-administration of a triazole antifungal drug with these immunosuppressant drugs can potentially increase plasma concentrations of the immunosuppressant drugs, thereby resulting in toxicity, or upon discontinuation, inadvertently decrease the respective concentrations with increased risk of rejection or graft-versus-host disease. In this article, we review the evidence for the extent of inhibition of cytochrome P450 3A4 by each of these triazole antifungal drugs and assess their effects on cyclosporine, tacrolimus, and sirolimus. We also consider other factors affecting interactions of these two classes of drugs. Finally, we examine recommendations and strategies to evaluate and address those potential drug-drug interactions in these patients.

An assessment of chemical contaminants in sediments from the St. Thomas East End Reserves, St. Thomas, USVI.

The St. Thomas East End Reserves or STEER is located on the southeastern end of the island of St. Thomas, USVI. The STEER contains extensive mangroves and seagrass beds, along with coral reefs, lagoons, and cays. Within the watershed, however, are a large active landfill, numerous marinas, resorts, various commercial activities, an EPA Superfund Site, and residential areas, all of which have the potential to contribute pollutants to the STEER. As part of a project to develop an integrated assessment for the STEER, 185 chemical contaminants were analyzed in sediments from 24 sites. Higher levels of chemical contaminants were found in Mangrove Lagoon and Benner Bay in the western portion of the study area. The concentrations of polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), zinc, copper, lead, and mercury were above a NOAA Effects Range-Low (ERL) sediment quality guideline at one or more sites, indicating impacts may be present in more sensitive species or life stages. Copper at one site in Benner Bay was above a NOAA Effects Range-Median (ERM) guideline indicating effects on benthic organisms were likely. The antifoulant boat hull ingredient tributyltin (TBT) was found at the third highest concentration in the history of NOAA's National Status and Trends (NS&T) Program, which monitors the nation's coastal and estuarine waters for chemical contaminants and bioeffects. The results from this project will provide resource managers with key information needed to make effective decisions affecting coral reef ecosystem health and gauge the efficacy of restoration activities.

Dyslipidaemia in women with polycystic ovary syndrome referred to a teaching hospital in Cape Town, South Africa.

The polycystic ovary syndrome (PCOS) imparts health risks including dyslipidaemia, diabetes and cardiovascular disease that are amenable to lifestyle adjustment and/or medication. We describe dyslipidaemia in women referred to a gynaecological endocrine clinic. Clinical data and endocrine and lipoprotein investigations comprising fasting triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLC) and calculated low density lipoprotein cholesterol (LDLC) were studied along with electrophoresis patterns of apolipoprotein B-containing lipoproteins. The 1721 participants comprised black, mixed ancestry, white and Indian individuals (9.8%, 83.2%, 5.8% and 1.2%, respectively). The mean ± standard deviation of the age, body mass index (BMI) and waist/hip ratio were 26.0 ± 5.9 years, 32.3 ± 8.3 kg/m2 and waist/hip ratio 0.88 ± 0.11, respectively. Overweight status (BMI 26-30 kg/m2) and obesity (BMI >30 kg/m2) involved 272 (15.8%) and 1010 (58.7%) individuals, respectively. Morbid obesity (BMI >40 kg/m2) was present in 309 (17.9%) individuals. The TG, TC, HDLC and LDLC concentrations were 1.22 ± 0.86, 4.77 ± 1.02, 1.3 ± 0.36, 2.94 ± 0.94 mmol/L, respectively. LDL hypercholesterolaemia occurred in 753 (43.7%) and exceeded 5 mmol/L in 39 (2.3%) women. Low HDLC (<0.9 mmol/L) affected 122 (7%), hypertriglyceridaemia (>1.7 mmol/L) affected 265 (15.4%) and exceeded 2.5 mmol/L in 91 (5.3%) women. Mixed hyperlipidaemia (TG >1.7, TC >5.0 mmol/L) occurred in 176 (10.2%). Electrophoresis revealed small LDL particles in 79 (4.6%) and dysbetalipoproteinaemia in 13 (0.76%) of the cohort. Small LDL associated with obesity, blood pressure, TG and glucose concentration and higher androgenic state. Many women with PCOS had unfavourable lipoprotein results: mostly moderate changes in TG, HDLC and LDLC. Small LDL is not rare, may aid risk assessment and is best determined directly. Incidental monogenic disorders of lipoprotein metabolism included dysbetalipoproteinaemia, familial hypercholesterolaemia and severe hypertriglyceridaemia. Dyslipidaemia in PCOS requires more careful diagnosis, individualised management and research.

Comparison of a hepatitis C core antigen assay to nucleic acid amplification testing for detection of hepatitis C viremia in a US population.

The prevalence of hepatitis C virus (HCV) infection in the United States has increased over the past decade despite the development of effective direct-acting antiviral treatments. To meet the World Health Organization's (WHO) goal of eliminating HCV infection by 2030, transmission events must be reduced. Currently, infection screening relies on detection of HCV antibodies, with nucleic acid amplification testing (NAAT) used to confirm HCV viremia and monitor changes in viral load. However, the seroconversion window for detection of HCV antibodies is long, averaging 6 weeks, with delayed seroconversion common in co-infected and immunosuppressed populations. Testing for HCV core antigen, which is present approximately 5 weeks before HCV antibodies, holds promise for earlier detection of HCV infection. It may also hold promise as a cheaper, more accessible, and more rapid alternative to NAAT for infection confirmation. Here, we evaluated the agreement between a research-use HCV Core Antigen Assay and NAAT among US patients receiving clinically indicated NAAT. Among 412 specimens, the overall concordance was 97.1%, with a positive percent agreement of 95.5%. Discrepancies primarily occurred among patients with chronic HCV and low viral loads; 11/12 discrepancies showed viral loads <4,000 IU/mL. Among patients being screened for HCV infection (i.e., excluding those undergoing NAAT for serial monitoring of a previously diagnosed infection), the positive percent agreement was 97.0%. Among patients undergoing serial testing, changes in HCV Core Antigen Assay signal-to-cut-off values were generally correlated with changes in the viral load. Results suggest that the research-use HCV Core Antigen Assay studied here may reliably detect and/or confirm HCV infection. IMPORTANCE: A research-use HCV Core Antigen Assay showed high concordance with nucleic acid amplification testing for the detection of current hepatitis C infection. The assay may enable more rapid and lower-cost detection and/or confirmation of hepatitis C infection.

Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue.

Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue.

Pediatric relapsed acute myeloid leukemia: a systematic review.

Introduction: Pediatric relapsed acute myeloid leukemia (AML) remains lethal in the majority of cases, despite intensive therapy. Randomized trials are largely lacking, and the main issues of optimal therapy and prognostic factors remain unclear. Area covered: This systematic review includes all literature evaluating treatment outcome after first relapse. We searched databases PubMed and Embase.com. Twelve out of six thousand articles were ultimately included, based on age of the population (<21 years), relapsed AML, and information on clinical outcome (second complete remission (CR2), disease-free survival (DFS), event-free survival (EFS) and overall survival (OS)). There was only one randomized clinical trial reported. This review shows that there is no standard treatment for relapsed AML in children, and that outcome varies for CR2 and (2- to 10-year) OS rates, mean 64% (range, 50-75%), and 31% (16-43%), respectively. Children treated with chemotherapy only in first complete remission (CR1) tend to have better outcome after relapse than children receiving allo-SCT in CR1. Allo-SCT seems to be the most effective consolidation therapy in children achieving CR2, after relapse. Duration of CR1 was the most frequently reported statistically significant prognostic factor. Through randomized clinical trials, better knowledge of prognostic factors enabling risk-stratified treatment, and of more effective and less toxic therapies, should contribute to better clinical outcome for children with relapsed AML. Expert opinion: Outcome of pediatric relapsed AML has improved to OS rates up to 40%. However, there is a lack of knowledge on (independent) prognostic factors, optimal reinduction chemotherapy, timing of allo-SCT, and late effects. International collaboration should enable large, randomized clinical trials addressing these issues.

Medical conditions associated with recurrent miscarriage-Is BMI the tip of the iceberg?

BACKGROUND: In contrast to sporadic miscarriage, recurrent miscarriage (RM) is a rare entity which affects 1% of couples attempting conception. It is distressing for couples and healthcare professionals as the aetiology is unclear with limited treatment options. Apart from anti-phospholipid syndrome (APS), the strength of associations between RM and commonly investigated endocrine, autoimmune, thrombophilic and uterine structural abnormalities remains uncertain and variable. OBJECTIVES: To assess the prevalence of commonly investigated medical conditions associated with RM. STUDY DESIGN: A 9-year retrospective analysis of a prospectively collected database was conducted for 592 patients seen between 2008 and 2016, in tertiary level RM clinic in South Africa. RESULTS: In this period, 592 patients were assessed. The mean age was 29.73±5.46 (mean±SD), gravidity 4.6±1.82 and parity 0.98±1.05. The mean number of miscarriages per patient was 3.34±1.63, of which two-thirds (61.3%) were in the first trimester, a third (33%) in the second trimester and intrauterine fetal deaths (IUFDs) constituted 6% of total losses. Of the 50% of patients with no identified associated disorders, 15% were unexplained (investigations complete but no associations found), 10% became pregnant during investigation (investigations incomplete) and 25% were lost to follow-up (investigations incomplete). Nearly forty percent (38%) of patients had an associated endocrine disorder (22% PCOS, 11% IGT, 3% Diabetes Mellitus and 2% Thyroid Dysfunction) and 10% a uterine factor (4% Cervical Incompetence, 2% Fibroids, 2% Synechiae and 2% Anomalies). APS and Thrombophilias constituted 3% and 2% of patients respectively. The BMI (mean±SD) amongst patients with Unexplained RM, PCOS and IGT were 28.85±5.95, 30.86±7.79 and 33.40±6.47 respectively. Patients with IGT had significantly higher mean BMI in comparison to those with Unexplained RM (p<0.0001)*** and PCOS (p<0.001)**. CONCLUSION: PCOS, IGT and Type II Diabetes are all likely surrogates for elevated BMI and constitute 70% of those women with RM and identified associated medical disorders. In our population, BMI seems to have a substantial impact on recurrent pregnancy loss and future studies should interrogate its effect on recurrent miscarriage.

Writing siblings: Alice James and her brothers.

This essay addresses the relationship of writing to embodiment, through representations of bodily sensation and fantasy in the journal of Alice James. It considers Alice James's writing in relation to her two writer brothers, William and Henry, and in light of their father's experiences of impairment and breakdown.

Reproductive knowledge and use of contraception among women with diabetes.

BACKGROUND: Poorly controlled diabetes is associated with poor maternal and fetal outcomes, yet many women become pregnant before establishing control. Reducing unintended pregnancies is a vital step towards improving perinatal and maternal morbidity and mortality. OBJECTIVES: To assess the reproductive knowledge and use of contraception in women of reproductive age attending diabetes outpatient clinics. METHODS: A prospective descriptive study was conducted of women known to have diabetes, aged 18 - 45 years, attending the diabetic clinics at Groote Schuur Hospital or the local community health centres in Cape Town, South Africa. A questionnaire consisting of social, demographic and family details as well as contraceptive use and knowledge was administered. RESULTS: Some common themes emerged, namely that 44.2% of the women with previous pregnancies had had unintended pregnancies, and that this was more common among single (58.8%) and younger women. Women with type 1 diabetes had better knowledge than those with type 2 diabetes of how pregnancy affects diabetes, but better knowledge did not translate to better contraception use. Despite the fact that 102 participants (88.7%) attended diabetes clinics two or more times a year, knowledge of pregnancy- and reproductive health-related complications was limited, and only 30 participants (26.1%) had received advice on contraception at these clinics. CONCLUSION: Knowledge about the impact of diabetes on pregnancy and that of pregnancy on diabetes was suboptimal. We recommend that reproductive health services be included at the routine diabetes clinic visit.