Filamin A (FLNA) mutation—A newcomer to the childhood interstitial lung disease (ChILD) classification

AIM: Interstitial lung disease (ILD) in infants represents a rare and heterogenous group of disorders, distinct from those occurring in adults. In recent years a new entity within this category is being recognized, namely filamin A (FLNA) mutation related lung disease. Our aims are to describe the clinical and radiological course of patients with this disease entity to aid clinicians in the prognostic counseling and management of similar patients they may encounter. METHOD: A retrospective case note review was conducted of all patients treated at our institution (a specialist tertiary referral childrens’ center) for genetically confirmed FLNA mutation related lung disease. The clinical presentation, evolution, management and radiological features were recorded and a medical literature review of Medline indexed articles was conducted. RESULTS: We present a case series of four patients with interstitial lung disease and genetically confirmed abnormalities within the FLNA gene. Their imaging findings all reveal a pattern of predominantly upper lobe overinflation, coarse pulmonary lobular septal thickening and diffuse patchy atelectasis. The clinical outcomes of our patients have been variable ranging from infant death, lobar resection and need for supplemental oxygen and bronchodilators. CONCLUSION: The progressive nature of the pulmonary aspect of this disorder and need for early aggressive supportive treatment make identification crucial to patient management and prognostic counseling

HIV Risk Profiles Among HIV-Positive, Methamphetamine-Using Men Who Have Sex with Both Men and Women

This study examined demographic characteristics, sexual risk behaviors, sexual beliefs, and substance use patterns in HIV-positive, methamphetamine-using men who have sex with both men and women (MSMW) (n = 50) as compared to men who have sex with men only (MSM) (n = 150). Separate logistic regressions were conducted to predict group membership. In the final model, of 12 variables, eight were independently associated with group membership. Factors independently associated with MSMW were acquiring HIV through injection drug use, being an injection drug user, using hallucinogens, using crack, being less likely to have sex at a bathhouse, being less likely to be the receptive partner when high on methamphetamine, having greater intentions to use condoms for oral sex, and having more negative attitudes about HIV disclosure. These results suggest that, among HIV-positive methamphetamine users, MSMW differ significantly from MSM in terms of their HIV risk behaviors. Studies of gay men and HIV often also include bisexual men, grouping them all together as MSM, which may obscure important differences between MSMW and MSM. It is important that future studies consider MSM and MSMW separately in order to expand our knowledge about differential HIV prevention needs for both groups. This study showed that there were important differences in primary and secondary prevention needs of MSM and MSMW. These findings have implications for both primary and secondary HIV prevention among these high-risk populations

Validation of World Health Organisation HIV/AIDS Clinical Staging in Predicting Initiation of Antiretroviral Therapy and Clinical Predictors of Low CD4 Cell Count in Uganda

IntroductionThe WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200 cells/mm(3), it has not been evaluated at for CD4 cut-offs of <250 cells/mm(3) or <350 cells/mm(3).ObjectiveTo validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda.ResultsData was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3%) were classified as in stages 1 and 2 and 262 (68%) were females. Participants had a mean age of 36.8 years (SD 8.5). We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm(3) and 350 cells/mm(3) was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2.ConclusionThe WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda

Affective Correlates of Stimulant Use and Adherence to Anti-retroviral Therapy Among HIV-positive Methamphetamine Users

The use of stimulants has important implications for HIV prevention and care. However, few investigations have examined psychological correlates of substance use and adherence to anti-retroviral therapy (ART) among HIV-positive stimulant users. This cross-sectional investigation examined affective correlates of stimulant use and ART adherence among HIV-positive methamphetamine users. In total, 122 HIV-positive men who have sex with men or transgendered individuals on ART who reported using methamphetamine in the past 30 days were recruited from the community. HIV-specific traumatic stress was consistently and independently associated with more frequent cocaine/crack use (but not with methamphetamine use). Positive affect was independently associated with a decreased likelihood of reporting any injection drug use and an increased likelihood of reporting perfect ART adherence. HIV-specific traumatic stress may be an important determinant of increased cocaine/crack use in this population. Positive affect may increase the likelihood that individuals will refrain from injection drug use and achieve high levels of ART adherence

Methamphetamine Use among Newly Diagnosed HIV-Positive Young Men in North Carolina, United States, from 2000 to 2005

Methamphetamine (MA) is a new arrival to the Southeastern United States (US). Incidence of HIV is also increasing regionally, but data are limited regarding any association between this trend and MA use. We examined behavioral data from North Carolina (NC) residents newly diagnosed with HIV, collected by the Department of Health between 2000-2005.Among 1,460 newly diagnosed HIV-positive young men, an increasing trend was seen from 2000-2005 in MA use (p = 0.01, total n = 20). In bivariate analyses, users of MA had significantly greater odds of reporting other substance use, including alcohol, powder or crack cocaine, marijuana, and methylenedioxymethamphetamine (MDMA, "ecstasy"). They were also more likely to have reported sexual activity while traveling outside NC; sex with anonymous partners; and previous HIV testing. In a predictive model, MA use had a negative association with nonwhite race, and strong positive associations with powder cocaine, "ecstasy," or intravenous drug use and being a university student.Similar to trends seen in more urban parts of the US, MA use among newly diagnosed, HIV-positive young men is increasing in NC. These data are among the first to demonstrate this relationship in a region with a burgeoning epidemic of MA use. Opportunities exist for MA-related HIV risk-reduction interventions whenever young men intersect the healthcare system

Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptors (PPARs) have emerged as important drug targets for diabetes. Drugs that activate PPARγ, such as the thiazolidinediones (TZDs), are widely used for treatment of Type 2 diabetes mellitus. PPARγ signaling could also play an anti-neoplastic role in several <it>in vitro </it>models, although conflicting results are reported from <it>in vivo </it>models. The effects of TZDs on cancer risk in humans needs to be resolved as these drugs are prescribed for long periods of time in patients with diabetes.</p> <p>Methods</p> <p>A total of 1003 subjects in community practice settings were interviewed at home at the time of enrolment into the Vermont Diabetes Information System, a clinical decision support program. Patients self-reported their personal and clinical characteristics, including any history of malignancy. Laboratory data were obtained directly from the clinical laboratory and current medications were obtained by direct observation of medication containers. We performed a cross-sectional analysis of the interviewed subjects to assess a possible association between cancer diagnosis and the use of TZDs.</p> <p>Results</p> <p>In a multivariate logistic regression model, a diagnosis of cancer was significantly associated with TZD use, even after correcting for potential confounders including other oral anti-diabetic agents (sulfonylureas and biguanides), age, glycosylated hemoglobin A1C, body mass index, cigarette smoking, high comorbidity, and number of prescription medications (odds ratio = 1.59, <it>P </it>= 0.04). This association was particularly strong among patients using rosiglitazone (OR = 1.89, <it>P </it>= 0.02), and among women (OR = 2.07, <it>P </it>= 0.01).</p> <p>Conclusion</p> <p>These data suggest an association between TZD use and cancer in patients with diabetes. Further studies are required to determine if this association is causal.</p

Detection and quantification of antibody to SARS CoV 2 receptor binding domain provides enhanced sensitivity, specificity and utility

Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based confirmatory and reference activity. The viral receptor binding domain (RBD) constitutes the prime target antigen for neutralising antibody. A double antigen binding assay (DABA), providing the most sensitive format has been exploited in a novel hybrid manner employing a solid-phase S1 preferentially presenting RBD, coupled with a labelled RBD conjugate, used in a two-step sequential assay for detection and measurement of antibody to RBD (anti-RBD). This class and species neutral assay showed a specificity of 100% on 825 pre COVID-19 samples and a potential sensitivity of 99.6% on 276 recovery samples, predicting quantitatively the presence of neutralising antibody determined by pseudo-type neutralisation and by plaque reduction. Anti-RBD is also measurable in ferrets immunised with ChadOx1 nCoV-19 vaccine and in humans immunised with both AstraZeneca and Pfizer vaccines. This assay detects anti-RBD at presentation with illness, demonstrates its elevation with disease severity, its sequel to asymptomatic infection and its persistence after the loss of antibody to the nucleoprotein (anti-NP). It also provides serological confirmation of prior infection and offers a secure measure for seroprevalence and studies of vaccine immunisation in human and animal populations. The hybrid DABA also displays the attributes necessary for the detection and quantification of anti-RBD to be used in clinical practice. An absence of detectable anti-RBD by this assay predicates the need for passive immune prophylaxis in at-risk patients

Regions of High Out-Of-Hospital Cardiac Arrest Incidence and Low Bystander CPR Rates in Victoria, Australia

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a major public health issue and research has shown that large regional variation in outcomes exists. Of the interventions associated with survival, the provision of bystander CPR is one of the most important modifiable factors. The aim of this study is to identify census areas with high incidence of OHCA and low rates of bystander CPR in Victoria, Australia. METHODS: We conducted an observational study using prospectively collected population-based OHCA data from the state of Victoria in Australia. Using ArcGIS (ArcMap 10.0), we linked the location of the arrest using the dispatch coordinates (longitude and latitude) to Victorian Local Government Areas (LGAs). We used Bayesian hierarchical models with random effects on each LGA to provide shrunken estimates of the rates of bystander CPR and the incidence rates. RESULTS: Over the study period there were 31,019 adult OHCA attended, of which 21,436 (69.1%) cases were of presumed cardiac etiology. Significant variation in the incidence of OHCA among LGAs was observed. There was a 3 fold difference in the incidence rate between the lowest and highest LGAs, ranging from 38.5 to 115.1 cases per 100,000 person-years. The overall rate of bystander CPR for bystander witnessed OHCAs was 62.4%, with the rate increasing from 56.4% in 2008-2010 to 68.6% in 2010-2013. There was a 25.1% absolute difference in bystander CPR rates between the highest and lowest LGAs. CONCLUSION: Significant regional variation in OHCA incidence and bystander CPR rates exists throughout Victoria. Regions with high incidence and low bystander CPR participation can be identified and would make suitable targets for interventions to improve CPR participation rates

Acute bronchiolitis in infancy as risk factor for wheezing and reduced pulmonary function by seven years in Akershus County, Norway

BACKGROUND: Acute viral bronchiolitis is one of the most common causes of hospitalisation during infancy in our region with respiratory syncytial virus (RSV) historically being the major causative agent. Many infants with early-life RSV bronchiolitis have sustained bronchial hyperreactivity for many years after hospitalisation and the reasons for this are probably multifactorial. The principal aim of the present study was to investigate if children hospitalised for any acute viral bronchiolitis during infancy in our region, and not only those due to RSV, had more episodes of subsequent wheezing up to age seven years and reduced lung function at that age compared to children not hospitalised for acute bronchiolitis during infancy. A secondary aim was to compare the hospitalised infants with proven RSV bronchiolitis (RS+) to the hospitalised infants with non-RSV bronchiolitis (RS-) according to the same endpoints. METHODS: 57 infants hospitalised at least once with acute viral bronchiolitis during two consecutive winter seasons in 1993–1994 were examined at age seven years. An age-matched control group of 64 children, who had not been hospitalised for acute viral bronchiolitis during infancy, were recruited from a local primary school. Epidemiological and clinical data were collected retrospectively from hospital discharge records and through structured clinical interviews and physical examinations at the follow-up visit. RESULTS: The children hospitalised for bronchiolitis during infancy had decreased lung function, more often wheezing episodes, current medication and follow-up for asthma at age seven years than did the age matched controls. They also had lower average birth weight and more often first order family members with asthma. We did not find significant differences between the RSV+ and RSV- groups. CONCLUSION: Children hospitalised for early-life bronchiolitis are susceptible to recurrent wheezing and reduced pulmonary function by seven years compared to age-matched children not hospitalised for early-life bronchiolitis. We propose that prolonged bronchial hyperreactivity could follow early-life RSV negative as well as RSV positive bronchiolitis