False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women

Objective: Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others). Design: To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008. Methods: Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status. Results: HIV prevalence was 0.06 % among 921,438 pregnant women and 1.34 % among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14 % vs. 0.21%, odds ratio 0.65 [95 % confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p,0.01) to have Western blot-negative (52.9 % vs. 9.8%) and indeterminate results (17.0 % vs. 3.7%) and lower PPV (30 % vs. 87%). The p24 band was detected more often among pregnant women (p,0.01). Conclusions: False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others

Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome

Scalp-ear-nipple (SEN) syndrome is a rare, autosomal-dominant disorder characterized by cutis aplasia of the scalp; minor anomalies of the external ears, digits, and nails; and malformations of the breast. We used linkage analysis and exome sequencing of a multiplex family affected by SEN syndrome to identify potassium-channel tetramerization-domain-containing 1 (KCTD1) mutations that cause SEN syndrome. Evaluation of a total of ten families affected by SEN syndrome revealed KCTD1 missense mutations in each family tested. All of the mutations occurred in a KCTD1 region encoding a highly conserved bric-a-brac, tram track, and broad complex (BTB) domain that is required for transcriptional repressor activity. KCTD1 inhibits the transactivation of the transcription factor AP-2 alpha (TFAP2A) via its BTB domain, and mutations in TFAP2A cause cutis aplasia in individuals with branchiooculofacial syndrome (BOFS), suggesting a potential overlap in the pathogenesis of SEN syndrome and BOFS. the identification of KCTD1 mutations in SEN syndrome reveals a role for this BTB-domain-containing transcriptional repressor during ectodermal development.National Institutes of Health National Human Genome Research InstituteLife Sciences Discovery FundWashington Research FoundationMassachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USAUniv Washington, Dept Pediat, Seattle, WA 98195 USAUniv Washington, Dept Genome Sci, Seattle, WA 98195 USAUniv Western Sydney Macarthur, Sch Med, Campbelltown, NSW 2560, AustraliaGenet Learning Disabil Serv, Newcastle, NSW 2298, AustraliaJohns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USAUniversidade Federal de São Paulo, Dept Morphol & Genet, Clin Genet Ctr, BR-04021001 São Paulo, BrazilPontificia Univ Catolica Parana, Dept Internal Med, BR-1155 Curitiba, Parana, BrazilWestern Gen Hosp, South East Scotland Clin Genet Serv, Edinburgh EH4 2XU, Midlothian, ScotlandUniv Florence, Dept Genet & Mol Med, I-50132 Florence, ItalyHop Necker Enfants Malad, Dept Genet, INSERM, U781, F-75015 Paris, FranceUniv Paris Descartes Sorbonne Paris Cite, Inst Imagine, F-75015 Paris, FranceHop Cote Nacre, CHU Caen, Serv Genet, F-14033 Caen 9, FranceUniv Connecticut, Ctr Hlth, Dept Reconstruct Sci, Farmington, CT 06030 USABoston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USATreuman Katz Ctr Pediat Bioeth, Seattle Childrens Res Inst, Seattle, WA 98101 USAUniversidade Federal de São Paulo, Dept Morphol & Genet, Clin Genet Ctr, BR-04021001 São Paulo, BrazilNational Institutes of Health National Human Genome Research Institute: 1U54HG006493National Institutes of Health National Human Genome Research Institute: 1RC2HG005608National Institutes of Health National Human Genome Research Institute: 5RO1HG004316Life Sciences Discovery Fund: 2065508Life Sciences Discovery Fund: 0905001Web of Scienc

Prospective association of social circumstance, socioeconomic, lifestyle and mental health factors with subsequent hospitalisation over 6-7 year follow up in people living with HIV.

BACKGROUND: Predictors of hospitalisation in people with HIV (PLHIV) in the contemporary treatment era are not well understood. METHODS: This ASTRA sub-study used clinic data linkage and record review to determine occurrence of hospitalisations among 798 PLHIV from baseline questionnaire (February to December 2011) until 1 June 2018. Associations of baseline social circumstance, socioeconomic, lifestyle, mental health, demographic and clinical factors with repeated all-cause hospitalisation from longitudinal data were investigated using Prentice-Williams-Peterson models. Associations were also assessed in 461 individuals on antiretroviral therapy (ART) with viral load ≤50 copies/ml and CD4 count ≥500 cells/ µl. FINDINGS: Rate of hospitalisation was 5.8/100 person-years (95% CI: 5.1-6.5). Adjusted for age, demographic group and time with diagnosed HIV, the following social circumstance, socioeconomic, lifestyle and mental health factors predicted hospitalisation: no stable partner (adjusted hazard ratio (aHR)=1.59; 95% CI=1.16-2.20 vs living with partner); having children (aHR=1.50; 1.08-2.10); non-employment (aHR=1.56; 1.07-2.27 for unemployment; aHR=2.39; 1.70-3.37 for sick/disabled vs employed); rented housing (aHR=1.72; 1.26-2.37 vs homeowner); not enough money for basic needs (aHR=1.82; 1.19-2.78 vs enough); current smoking (aHR=1.39; 1.02-1.91 vs never); recent injection-drug use (aHR=2.11; 1.30-3.43); anxiety symptoms (aHRs=1.39; 1.01-1.91, 2.06; 1.43-2.95 for mild and moderate vs none/minimal); depressive symptoms (aHRs=1.67; 1.17-2.38, 1.91; 1.30-2.78 for moderate and severe vs none/minimal); treated/untreated depression (aHRs=1.65; 1.03-2.64 for treated depression only, 1.87; 1.39-2.52 for depressive symptoms only; 1.53; 1.05-2.24; for treated depression and depressive symptoms, versus neither). Associations were broadly similar in those with controlled HIV and high CD4. INTERPRETATION: Social circumstance, socioeconomic disadvantage, adverse lifestyle factors and poorer mental health are strong predictors of hospitalisation in PLHIV, highlighting the need for targeted interventions and care. FUNDING: British HIV Association (BHIVA) Research Award (2017); SMR funded by a PhD fellowship from the Royal Free Charity

Causes of hospitalisation among a cohort of people with HIV from a London centre followed from 2011 to 2018.

BACKGROUND: We describe the spectrum of ICD-10 classified causes for hospitalisations occurring between 2011 and 2018 in a cohort of people living with HIV (PLHIV). METHODS: This sub-study includes 798 PLHIV participating in the Antiretroviral, Sexual Transmission Risk and Attitudes (ASTRA) questionnaire study who were recruited from a large London centre. A medical record review identified the occurrence and causes of hospitalisation from the date of questionnaire completion (February-December 2011) until 1 June 2018. Up to five causes were classified by an HIV clinician using the ICD-10 system. RESULTS: There were 274 hospitalisations in 153 people (rate = 5.8/100 person-years; 95% CI: 5.1, 6.5). Causes were wide-ranging; the most common were circulatory (16.8%), digestive (13.1%), respiratory (11.7%), infectious diseases (11.0%), injury/poisoning (10.6%), genitourinary diseases (9.9%) and neoplasms (9.1%). A tenth (27/274) of hospitalisations were related to at least one AIDS-defining illness. Median duration of hospitalisation was 5 days (IQR 2-9). At the time of hospitalisation, median CD4 count was high (510 cells/μl; IQR: 315-739), while median CD4 nadir was relatively low (113 cells/μl; IQR: 40-239). At admission, half of individuals (51%) had a previous AIDS-defining illness and 21% had viral load > 50 copies/ml. Individuals admitted for infectious diseases were particularly likely to have unfavourable HIV-related clinical characteristics (low CD4, viral non-suppression, not on antiretroviral therapy (ART), previous AIDS). CONCLUSIONS: In the modern combination antiretroviral therapy era, the spectrum of causes of hospitalisation in PLHIV in the UK is wide-ranging, highlighting the importance of holistic care for PLHIV, including prevention, early detection and treatment of comorbidities

Patient Perspectives with Abbreviated versus Standard Pre-Test HIV Counseling in the Prenatal Setting: A Randomized-Controlled, Non-Inferiority Trial

In the US, an unacceptably high percentage of pregnant women do not undergo prenatal HIV testing. Previous studies have found increased uptake of prenatal HIV testing with abbreviated pre-test counseling, however little is known about patient decision making, testing satisfaction and knowledge in this setting.A randomized-controlled, non-inferiority trial was conducted from October 2006 through February 2008 at San Francisco General Hospital (SFGH), the public teaching hospital of the City and County of San Francisco. A total of 278 English- and Spanish-speaking pregnant women were randomized to receive either abbreviated or standard nurse-performed HIV test counseling at the initial prenatal visit. Patient decision making experience was compared between abbreviated versus standard HIV counseling strategies among a sample of low-income, urban, ethnically diverse prenatal patients. The primary outcome was the decisional conflict score (DCS) using O'Connor low-literacy scale and secondary outcomes included satisfaction with test decision, basic HIV knowledge and HIV testing uptake. We conducted an intention-to-treat analysis of 278 women--134 (48.2%) in the abbreviated arm (AA) and 144 (51.8%) in the standard arm (SA). There was no significant difference in the proportion of women with low decisional conflict (71.6% in AA vs. 76.4% in SA, p = .37), and the observed mean difference between the groups of 3.88 (95% CI: -0.65, 8.41) did not exceed the non-inferiority margin. HIV testing uptake was very high (97. 8%) and did not differ significantly between the 2 groups (99.3% in AA vs. 96.5% in SA, p = .12). Likewise, there was no difference in satisfaction with testing decision (97.8% in AA vs. 99.3% in SA, p = .36). However, women in AA had significantly lower mean HIV knowledge scores (78.4%) compared to women in SA (83.7%, p<0.01).This study suggests that streamlining the pre-test counseling process, while associated with slightly lower knowledge, does not compromise patient decision making or satisfaction regarding HIV testing.ClinicalTrials.gov NCT00503308

Challenges of self-reported medical conditions and electronic medical records among members of a large military cohort

<p>Abstract</p> <p>Background</p> <p>Self-reported medical history data are frequently used in epidemiological studies. Self-reported diagnoses may differ from medical record diagnoses due to poor patient-clinician communication, self-diagnosis in the absence of a satisfactory explanation for symptoms, or the "health literacy" of the patient.</p> <p>Methods</p> <p>The US Department of Defense military health system offers a unique opportunity to evaluate electronic medical records with near complete ascertainment while on active duty. This study compared 38 self-reported medical conditions to electronic medical record data in a large population-based US military cohort. The objective of this study was to better understand challenges and strengths in self-reporting of medical conditions.</p> <p>Results</p> <p>Using positive and negative agreement statistics for less-prevalent conditions, near-perfect negative agreement and moderate positive agreement were found for the 38 diagnoses.</p> <p>Conclusion</p> <p>This report highlights the challenges of using self-reported medical data and electronic medical records data, but illustrates that agreement between the two data sources increases with increased surveillance period of medical records. Self-reported medical data may be sufficient for ruling out history of a particular condition whereas prevalence studies may be best served by using an objective measure of medical conditions found in electronic healthcare records. Defining medical conditions from multiple sources in large, long-term prospective cohorts will reinforce the value of the study, particularly during the initial years when prevalence for many conditions may still be low.</p

Inverse association of antioxidant and phytoestrogen nutrient intake with adult glioma in the San Francisco Bay Area: a case-control study

BACKGROUND: Increasing evidence from epidemiologic studies suggest that oxidative stress may play a role in adult glioma. In addition to dietary antioxidants, antioxidant and weak estrogenic properties of dietary phytoestrogens may attenuate oxidative stress. Our hypothesis is that long-term consumption of dietary antioxidants and phytoestrogens such as genistein, daidzein, biochanin A, formononetin, matairesinol, secoisolariciresinol and coumestrol, may reduce the risk of adult glioma. METHODS: Using unconditional logistic regression models, we compared quartiles of consumption for several specific antioxidants and phytoestrogens among 802 adult glioma cases and 846 controls from two study series from the San Francisco Bay Area Adult Glioma Study, 1991 – 2000, controlling for vitamin supplement usage, age, socioeconomic status, gender, ethnicity and total daily calories. For cases, dietary information was either self-reported or reported by a proxy. For controls, dietary information was self-reported. Gender- and series- specific quartiles of average daily nutrient intake, estimated from food-frequency questionnaires, were computed from controls. RESULTS: Significant p-values (trend test) were evaluated using significance levels of either 0.05 or 0.003 (the Bonferroni corrected significance level equivalent to 0.05 adjusting for 16 comparisons). For all cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.003), carotenoids (alpha- and beta-carotene combined, p < 0.05), daidzein (p = 0.003), matairesinol (p < 0.05), secoisolariciresinol (p < 0.003), and coumestrol (p < 0.003). For self-reported cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.05) and daidzein (p < 0.05). CONCLUSION: Our results support inverse associations of glioma with higher dietary antioxidant index and with higher intake of certain phytoestrogens, especially daidzein

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

Virally suppressed HIV-positive individuals on combination antiretroviral therapy who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality. The increased mortality was seen across different patient groups and for all causes of deat