Comorbidity in young patients with juvenile systemic lupus erythematosus: how can we improve management?

Clinical Rheumatology -     

Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene

We performed gene–environment interaction genome-wide association analysis (G × E GWAS) to identify SNPs whose effects on metabolic traits are modified by chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis (MESA). In Whites, the G × E GWAS for hip circumference identified five SNPs within the Early B-cell Factor 1 (EBF1) gene, all of which were in strong linkage disequilibrium. The gene-by-stress interaction (SNP × STRESS) term P-values were genome-wide significant (Ps=7.14E−09 to 2.33E−08, uncorrected; Ps=1.99E−07 to 5.18E−07, corrected for genomic control). The SNP-only (without interaction) model P-values (Ps=0.011–0.022) were not significant at the conventional genome-wide significance level. Further analysis of related phenotypes identified gene-by-stress interaction effects for waist circumference, body mass index (BMI), fasting glucose, type II diabetes status, and common carotid intimal–medial thickness (CCIMT), supporting a proposed model of gene-by-stress interaction that connects cardiovascular disease (CVD) risk factor endophenotypes such as central obesity and increased blood glucose or diabetes to CVD itself. Structural equation path analysis suggested that the path from chronic psychosocial stress to CCIMT via hip circumference and fasting glucose was larger (estimate=0.26, P=0.033, 95% CI=0.02–0.49) in the EBF1 rs4704963 CT/CC genotypes group than the same path in the TT group (estimate=0.004, P=0.34, 95% CI=−0.004–0.012). We replicated the association of the EBF1 SNPs and hip circumference in the Framingham Offspring Cohort (gene-by-stress term P-values=0.007–0.012) as well as identified similar path relationships. This observed and replicated interaction between psychosocial stress and variation in the EBF1 gene may provide a biological hypothesis for the complex relationship between psychosocial stress, central obesity, diabetes, and cardiovascular disease.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.     

Serum pepsinogens as markers of response to therapy forHelicobacter pylori gastritis

We have investigated the effect of therapy forHelicobacter pylori gastritis on serum concentrations of pepsinogen I and II in 43 patients. In the 22 patients in whom therapy resulted in dramatic decrease in gastritis scores and in clearance of the bacteria, there was a highly significant (P=0.0001) fall in mean serum pepsinogen II from 13.3±0.8 to 7.9±0.7 μg/liter, and a less pronounced fall in pepsinogen I from 89.0±5.9 to 78.5±0.4 μg/liter (P=0.01). These changes resulted in a significant (P=0.01) increase in the pepsinogen I/II ratio. In contrast, nonsignificant declines of 3.5% and 11.6% were observed in mean pepsinogen I and II levels in the 21 patients whose gastritis failed to resolve histologically and whose infection did not clear. These findings suggest that serum pepsinogen levels, especially pepsinogen II, are a new tool that may be found to be clinically useful in evaluation of treatment outcome in patients withH. pylori-associated gastritis.     

Designing a Primary Care–Based Deprescribing Intervention for Patients with Dementia and Multiple Chronic Conditions: a Qualitative Study

BackgroundPatients with dementia and multiple chronic conditions (MCC) frequently experience polypharmacy, increasing their risk of adverse drug events.ObjectivesTo elucidate patient, family, and physician perspectives on medication discontinuation and recommended language for deprescribing discussions in order to inform an intervention to increase awareness of deprescribing among individuals with dementia and MCC, family caregivers and primary care physicians. We also explored participant views on culturally competent approaches to deprescribing.DesignQualitative approach based on semi-structured interviews with patients, caregivers, and physicians.ParticipantsPatients aged ≥ 65 years with claims-based diagnosis of dementia, ≥ 1 additional chronic condition, and ≥ 5 chronic medications were recruited from an integrated delivery system in Colorado and an academic medical center in Maryland. We included caregivers when present or if patients were unable to participate due to severe cognitive impairment. Physicians were recruited within the same systems and through snowball sampling, targeting areas with large African American and Hispanic populations.ApproachWe used constant comparison to identify and compare themes between patients, caregivers, and physicians.Key ResultsWe conducted interviews with 17 patients, 16 caregivers, and 16 physicians. All groups said it was important to earn trust before deprescribing, frame deprescribing as routine and positive, align deprescribing with goals of dementia care, and respect caregivers’ expertise. As in other areas of medicine, racial, ethnic, and language concordance was important to patients and caregivers from minority cultural backgrounds. Participants favored direct-to-patient educational materials, support from pharmacists and other team members, and close follow-up during deprescribing. Patients and caregivers favored language that explained deprescribing in terms of altered physiology with aging. Physicians desired communication tips addressing specific clinical situations.ConclusionsCulturally sensitive communication within a trusted patient-physician relationship supplemented by pharmacists, and language tailored to specific clinical situations may support deprescribing in primary care for patients with dementia and MCC.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06063-y) contains supplementary material, which is available to authorized users.KEY WORDS: deprescribing, patient-physician communication, dementia     

Human rhinovirus C infections in pediatric hematology and oncology patients

Children with cancer and HSCT recipients are at high risk for common viral infections. We sought to define the viral etiology of ARI and identify risk factors. Nasal wash samples were collected from pediatric hematology–oncology patients and HSCT recipients with ARI during the 2003–2005 winter seasons. Real‐time RT‐PCR was performed to detect Flu A, influenza B, RSV, PIV 1‐3, human MPV, and HRV. HRV specimens were sequenced and genotyped. Seventy‐eight samples from 62 children were included. Viruses were detected in 31 of 78 samples (40%). HRV were detected most frequently, in 16 (52%) including five HRVC; followed by seven (22%) RSV, five (16%) Flu A, four (13%) MPV, and two (6%) PIV2. There was a trend toward higher risk of viral infection for children in day care. Only 8% of the study children had received influenza vaccine. HRV, including the recently discovered HRVC, are an important cause of infection in pediatric oncology and HSCT patients. Molecular testing is superior to conventional methods and should be standard of care, as HRV are not detected by conventional methods.     

Executive functioning in preschool-age children prenatally exposed to alcohol,cocaine, and marijuana

BACKGROUND: Reports from clinical and experimental (animal) research converge on the suggestion that prenatal exposure to alcohol, cocaine, or marijuana undermines executive functioning (EF) and its neurological underpinnings. However, large, adequately controlled, prospective studies of alcohol and marijuana effects on EF have reported conflicting findings, and there have been no such studies of cocaine exposure. METHODS: EF was investigated in a cohort (n = 316) of 4-year-old children the majority of whose mothers had used varying combinations of cocaine, alcohol, and marijuana during pregnancy. With use of postpartum maternal report and biological assay, children were assigned to overlapping prenatal cocaine-exposed, alcohol-exposed, and marijuana-exposed groups and to complementary control groups. The postnatal environmental assessment included measures of maternal intellectual and psychosocial functioning, current drug or alcohol use, and home environment. RESULTS: The children in the alcohol-exposed group had worse tapping-inhibition performance than children in the non-alcohol-exposed group, and this effect persisted when potential confounding environmental variables, other drug variables, and concurrent verbal intelligence were controlled for. CONCLUSIONS: Prenatal alcohol is predictive of decreased EF in early childhood that could not be attributed to environmental factors. The results are discussed in terms of the age and overall high-risk status of the children.