Home-based HIV Testing for Children: A Useful Complement for Caregivers with More Children, Who are Male, and with an HIV Negative Partner.

Expanding index and family-based testing (HBT) is a priority for identifying children living with HIV. Our study characterizes predictors that drive testing location choice for children of parents living with HIV. Kenyan adults living with HIV were offered a choice of HBT or clinic-based testing (CBT) for any of their children (0-12 years) of unknown HIV status. Multilevel generalized linear models were used to identify correlates of choosing HBT or CBT for children and testing all versus some children within a family, including caregiver demographics, HIV history, social support, cost, and child demographics and HIV prevention history. Among 244 caregivers living with HIV and their children of unknown HIV status, most (72%) caregivers tested children using CBT. In multivariate analysis, female caregivers [aRR 0.52 (95% CI 0.34-0.80)] were less likely to choose HBT than male caregivers. Caregivers with more children requiring testing [aRR 1.23 (95% CI 1.05-1.44)] were more likely to choose HBT than those with fewer children requiring testing. In subgroup univariate analysis, female caregivers with a known HIV negative spouse were significantly more likely to choose HBT over CBT than those with a known HIV positive spouse [RR 2.57 (95% CI 1.28-5.14), p = 0.008], no association was found for male caregivers. Child demographics and clinical history was not associated with study outcomes. Caregiver-specific factors were more influential than child-specific factors in caregiver choice of pediatric HIV testing location. Home-based testing may be preferable to families with higher child care needs and may encourage pediatric HIV testing if offered as an alternative to clinic testing.

Newly diagnosed HIV positive children: a unique index case to improve HIV diagnosis and linkage to care of parents.

Newly diagnosed HIV positive children may be unique index cases to identify undiagnosed parents. Data was used from the Pediatric Urgent Start of HAART (NCT02063880) trial, which enrolled hospitalized, ART-naïve, HIV positive children ages 0-12 years in Kenya. Exact McNemar's tests were used to compare proportions of mothers and fathers tested for HIV, linked to care, and on ART at baseline and 6 months. This analysis included 87 newly diagnosed children with HIV who completed 6 months of follow-up. Among 83 children with living mothers, there were improvements in maternal linkage to care and treatment comparing baseline to 6 months (36% vs. 78%; p < 0.0001 and 22% vs. 52%; p < 0.0001). Among 80 children with living fathers, there were increases from baseline to 6 months in the number of fathers who knew the child's HIV status (34% vs. 78%; p < 0.0001), fathers ever tested for HIV (43% vs. 65%; p < 0.0001), fathers ever tested HIV positive (21% vs. 43%; p < 0.0001), fathers ever linked to care (15% vs. 35%; p < 0.0001), and fathers ever initiated on ART (11% vs. 23%; p = 0.0039). Newly diagnosed HIV positive children can be important index cases to identify parents with undiagnosed HIV or poor engagement in care.

Pediatric and Adult Recommendations Vary for Sibling Testing in Cystic Fibrosis.

Four to 5 % of cystic fibrosis (CF) patients are diagnosed as adults and often have subtler symptoms. Their siblings are at genetic risk to also have a subtler disease state. Diagnostic testing is recommended for siblings of newly diagnosed infants, but recommendations are less clear for later diagnoses. This study explored sibling testing recommendations in pediatric and adult practice using a survey that was emailed to CF clinicians. There were 58 respondents. Results revealed that 82.5% of pediatric and 36.4% of adult care respondents reported always recommending diagnostic testing for siblings of a newly diagnosed patient. In adult care, another 33.3% reported recommending diagnostic testing if the sibling has symptoms. In pediatric care, whether the sibling had newborn screening was most influential. Most pediatric respondents prefer the sweat chloride test, while 40% in adult practice prefer familial mutation analysis. Perceived barriers included cost, insurance coverage and logistical concerns in both settings, parental emotional state in pediatrics, and concern making recommendations for someone who is not the patient in adult care. Genetic counselors may be able to meet familial needs in CF care, including sibling testing. Many newly diagnosed patients/families do not see a genetic counselor, especially in adult care. These data reveal opportunities for practice guidelines and standardization.

Only 32.3% of Breast Cancer Families with Pathogenic Variants in Cancer Genes Utilized Cascade Genetic Testing.

BACKGROUND: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The purpose of this study was to investigate the clinical use and implementation of cascade family testing (CFT) in families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs) in cancer-related predisposition genes. METHODS: Germline sequencing was carried out with NGS technology using a 52-gene panel, and cascade testing was performed by Sanger sequencing or MLPA. RESULTS: In a cohort of 1785 breast cancer patients (families), 20.3% were found to have PVs/LPVs. Specifically, 52.2%, 25.1%, and 22.7% of patients had positive findings in high-, intermediate-, and low-penetrance breast cancer susceptibility genes, respectively. Although CFT was recommended to all families, only 117 families (32.3%) agreed to proceed with genetic testing. Among the first-degree relatives who underwent CFT, 70.3% were female, and 108 of 121 (89.3%) were cancer free. Additionally, 42.7%, 36.7%, and 20.6% were offspring, siblings, and parents of the subject, respectively. Our data suggest that CFT was mostly undertaken (104/117, 88.8%) in families with positive findings in high-risk genes. CONCLUSIONS: Cascade family testing can be a powerful tool for primary cancer prevention by identifying at-risk family members. It is of utmost importance to implement genetic counseling approaches leading to increased awareness and communication of genetic testing results.

Presymptomatic diagnosis of Fabry's disease: a case report.

BACKGROUND: Fabry's disease is a rare X-linked genetic disorder characterized by reduced levels of the α-galactosidase A enzyme. It may present with a cardiac phenotype resembling hypertrophic cardiomyopathy. However, as a specific enzyme replacement therapy is available, it remains an important differential diagnoses in patients presenting with cardiac hypertrophy. In boys, onset has been reported in early childhood with complaints initially comprising neuropathic pain, reduced sweat production, and gastrointestinal symptoms. Later the cardiac, renal, and central nervous systems may become affected. Female mutation carriers may remain asymptomatic or present at a later age with varying symptoms and clinical manifestations due to random inactivation of the X chromosome in different organs. CASE PRESENTATION: Here we present a case of Fabry's disease diagnosed in the daughter of an elderly, Caucasian woman (81 years old) with late-onset cardiac conduction disease and heart failure. We discuss the implications of cascade screening relatives of elderly probands. CONCLUSIONS: Irrespective of the patient's age, physicians must be on the lookout for phenocopies when identifying patients with possibly inheritable cardiomyopathies. The specific - precise - diagnosis may be crucial for the patient as well as the relatives.