Hospital and community care costs for people newly diagnosed of living with HIV in London, UK.

This study of people newly diagnosed of living with HIV (ND-PLHIV) calculated the use, cost and outcome of HIV services at a London HIV centre. ND-PLHIV were followed July 2017-October 2018. Hospital data included inpatient days (IP), outpatient (OP), dayward (DW) visits, tests and procedures, and anti-retroviral drugs (ARVs). Community services were recorded in daily diaries. Mean per patient-year (MPPY) use was multiplied by unit costs. 13.6 MPPY (95%CI 12.4-14.9) OP visits, 0.4 MPPY (95%CI 0.1-0.7) IP days, 0.09 MPPY (95%CI 0.01-0.2) DW visits and 4.6 MPPY community services (95%CI 3.4-5.8). Total annual costs per patient-year (CPPY) was £11,483 (95%CI £10,369-12,597): ARVs comprised 63% and community services 2%. White participants used fewer hospital and more community services compared with minority ethnic community (MEC) participants. Costs for White ND-PLHIV was £10,778 CPPY (95%CI £9629-11,928); £13,214 (95%CI £10,656-15,772) for MEC ND-PLHIV (p < 0.06). Annual costs were inversely related to CD4 count at entry (r = -5.58, p = 0.02); mean CD4 count was 476 cells/mm3 (95%CI 422-531) versus 373 cells/mm3 (95%CI 320-425) for White and MEC participants respectively (p = 0.03). Annual costs for ND-PLHIV with CD4 ≤ 350 cells/mm3 was £2478 PPY higher compared with CD4 count >350 cells/mm3 (p = 0.04).

Memory support training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: a digital application supported intervention (Brain Boosters).

BACKGROUND: Evidence-based interventions to protect against cognitive decline among older adults at risk for Alzheimer's disease and related dementias (ADRD) are urgently needed. Rehabilitation approaches to support memory and behavioral/lifestyle interventions are recognized as promising strategies for preserving or improving cognitive health, although few previous interventions have combined both approaches. This paper describes the protocol of the Brain Boosters intervention, which synergistically combines training in compensatory and healthy lifestyle behaviors and supports implementation and tracking of new behaviors with a digital application. METHODS: The study utilizes a single-site, single-blinded, randomized controlled design to compare a structured lifestyle and compensatory aid intervention to an education-only self-guided intervention. We plan to enroll 225 community-dwelling adults (25% from underrepresented groups) aged 65 + who endorse subjective cognitive decline (SCD) and low baseline levels of healthy lifestyle behaviors. Both interventions will be administered in group format, consisting of 15 two-hour classes that occur weekly for ten weeks and taper to bi-monthly and monthly, for an intervention duration of 6 months. Participants in both interventions will receive education about a variety of memory support strategies and healthy lifestyle behaviors, focusing on physical and cognitive activity and stress management. The structured intervention will also receive support in adopting new behaviors and tracking set goals aided by the Electronic Memory and Management Aid (EMMA) digital application. Primary outcomes include global cognition (composite of memory, attention, and executive function tests) and everyday function (Everyday Cognition Questionnaire). Data will be collected at baseline and outcome visits, at approximately 6, 12, and 18 months. Qualitative interviews, self-report surveys (e.g., indicators of self-determination, health literacy) and EMMA data metrics will also be used to identify what components of the intervention are most effective and for whom they work. DISCUSSION: Successful project completion will provide valuable information about how individuals with SCD respond to a compensation and preventative lifestyle intervention assisted by a digital application, including an understanding of factors that may impact outcomes, treatment uptake, and adherence. The work will also inform development, scaling, and personalization of future interventions that can delay disability in individuals at risk for ADRD. TRIAL REGISTRATION: ClinicalTrials.gov. (NCT05027789, posted 8/30/2021).

Measuring High-Order Phonon Correlations in an Optomechanical Resonator.

We use single photon detectors to probe the motional state of a superfluid ^{4}He resonator of mass ∼1 ng. The arrival times of Stokes and anti-Stokes photons (scattered by the resonator's acoustic mode) are used to measure the resonator's phonon coherences up to the fourth order. By postselecting on photon detection events, we also measure coherences in the resonator when ≤3 phonons have been added or subtracted. These measurements are found to be consistent with predictions that assume the acoustic mode to be in thermal equilibrium with a bath through a Markovian coupling.

Tolerability of four-drug antiretroviral combination therapy in primary HIV-1 infection.

OBJECTIVES: Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV-1 infection (PHI). Four-drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four-drug regimens used in the Research in Viral Eradication of HIV-1 Reservoirs (RIVER) study. METHODS: At enrolment, ART-naïve adult participants or those newly commenced on ART were initiated or intensified to four-drug regimens within 4 weeks of PHI. Rapid start was defined as pre-confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient-reported adherence measured by 7-day recall and regimen switches between enrolment and randomization, respectively. RESULTS: Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV-1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV-1. Twenty (37%) started a four-drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable (viral load < 50 copies/mL), respectively. Adherence rates of 100% at weeks 4, 12, 22 and 24 were reported in 88.9%, 87.0%, 82.4% and 94.1% of participants, respectively. Five individuals switched to three drugs, four changed their regimen constituents, and two switched post-randomization. CONCLUSIONS: Overall, four-drug regimens were well tolerated and had high levels of adherence. Whilst their benefit over three-drug regimens is lacking, our findings should provide reassurance if a temporarily intensified regimen is clinically indicated to help facilitate treatment.

Characterizing copper and zinc content in forested wetland soils of North Carolina, USA.

Wetlands are often located in landscape positions where they receive runoff or floodwaters, which may contain toxic trace metals and other pollutants from anthropogenic sources. Over time, this can lead to the accumulation of potentially harmful levels of metals in wetlands soils. To assess the potential risk of Cu and Zn buildup in wetland soils in North Carolina, soil data from 88 wetlands were analyzed. In a subset of 16 wetlands, more intensive sampling was conducted. Samples were analyzed for Mehlich 3 Cu and Zn, and a subset of the samples was analyzed for total Cu and Zn. Overall, Mehlich 3 Cu and Zn were low, with mean values of 0.9 mg/kg for Cu and 3.2 mg/kg for Zn. Warning levels for Mehlich 3 Zn were only exceeded in three of the 88 sites; elevated Mehlich Cu was not observed. Total Cu and Zn were also low, with only a few sites having elevated levels; however, there was not a strong linear relationship between Mehlich 3 and total metals. Mean levels of Mehlich 3 Cu and Zn in wetlands were much lower than for human-impacted upland soils and background threshold concentrations that might be indicative of disturbance were much lower than warning levels for agricultural soils. The very low mobile Zn and Cu in most of these wetlands indicated that these metals do not pose a risk to the biota in most North Carolina wetlands, but wetlands with a direct and significant anthropogenic source of metal contamination could be exceptions.

Secukinumab-associated localized granuloma annulare (SAGA): a case report and review of the literature.

Granuloma annulare (GA) is a benign, usually self-limited inflammatory skin dermatosis characterized clinically by pink-red to brown dermal papules or annular plaques. The main histologic feature is the presence of palisading or interstitial granulomas composed of necrobiotic collagen, elastic fibers, and mucin surrounded by a lymphohistiocytic infiltrate. Granuloma annulare is commonly associated with trauma, infections, diabetes mellitus, dyslipidemia, malignancy, thyroid disease, and a variety of medications. Two cases of GA have been reported in association with the use of secukinumab, a monoclonal antibody directed against interleukin 17A (IL17A), for the treatment of moderate-to-severe plaque psoriasis. We report the third case of secukinumab-associated GA in a 52-year-old woman with a history of diabetes mellitus type II, dyslipidemia, and non-alcoholic steatohepatitis. After four months of therapy with secukinumab, she presented with pink papules coalescing to plaques involving the antecubital fossae. Histology demonstrated a lymphohistiocytic palisading granuloma with central necrobiotic collagen and mucin, consistent with GA. Physicians should be aware of the possibility of GA developing in patients receiving secukinumab, especially in those with predisposing factors for GA. A better understanding of secukinumab-associated GA may lead to discoveries in GA pathogenesis and reveal broader immunomodulatory effects of secukinumab.

Acute engagement of Gq-mediated signaling in the bed nucleus of the stria terminalis induces anxiety-like behavior.

The bed nucleus of the stria terminalis (BNST) is a brain region important for regulating anxiety-related behavior in both humans and rodents. Here we used a chemogenetic strategy to investigate how engagement of G protein-coupled receptor (GPCR) signaling cascades in genetically defined GABAergic BNST neurons modulates anxiety-related behavior and downstream circuit function. We saw that stimulation of vesicular γ-aminobutyric acid (GABA) transporter (VGAT)-expressing BNST neurons using hM3Dq, but neither hM4Di nor rM3Ds designer receptors exclusively activated by a designer drug (DREADD), promotes anxiety-like behavior. Further, we identified that activation of hM3Dq receptors in BNST VGAT neurons can induce a long-term depression-like state of glutamatergic synaptic transmission, indicating DREADD-induced changes in synaptic plasticity. Further, we used DREADD-assisted metabolic mapping to profile brain-wide network activity following activation of Gq-mediated signaling in BNST VGAT neurons and saw increased activity within ventral midbrain structures, including the ventral tegmental area and hindbrain structures such as the locus coeruleus and parabrachial nucleus. These results highlight that Gq-mediated signaling in BNST VGAT neurons can drive downstream network activity that correlates with anxiety-like behavior and points to the importance of identifying endogenous GPCRs within genetically defined cell populations. We next used a microfluidics approach to profile the receptorome of single BNST VGAT neurons. This approach yielded multiple Gq-coupled receptors that are associated with anxiety-like behavior and several potential novel candidates for regulation of anxiety-like behavior. From this, we identified that stimulation of the Gq-coupled receptor 5-HT2CR in the BNST is sufficient to elevate anxiety-like behavior in an acoustic startle task. Together, these results provide a novel profile of receptors within genetically defined BNST VGAT neurons that may serve as therapeutic targets for regulating anxiety states and provide a blueprint for examining how G-protein-mediated signaling in a genetically defined cell type can be used to assess behavior and brain-wide circuit function.

Uncertain diagnosis and prognosis in advanced melanoma: a qualitative study of the experiences of bereaved carers in a time of immune and targeted therapies.

BACKGROUND: Recent advances in advanced melanoma therapies are associated with improved survival for some patients. However, how patients with diagnoses of advanced disease and their carers experience this expanding treatment paradigm is not well understood. OBJECTIVES: To explore bereaved carers' accounts of the trajectory of advanced melanoma involving treatment by immune or targeted therapies, to build an understanding of their experiences of care relating to diagnosis and prognosis. METHODS: A qualitative exploratory design, using methods drawn from grounded theory, was adopted. Analyses drew on in-depth interviews with 20 bereaved carers from three metropolitan melanoma treatment centres in Australia. A flexible interview guide and structured approach to concurrent data collection and analysis were applied. RESULTS: Carers described qualities of the experience, including the shock of diagnosis after a sometimes-innocuous presentation with vague symptoms. They reported an unclear prognosis with complexity arising from interplay between an uncertain disease trajectory and often ambiguous expectations of outcomes of emerging immune and targeted therapies. Uncertainty dominated carers' experiences, increasing the complexity of care planning. CONCLUSIONS: Effective communication of an advanced melanoma diagnosis and prognosis is critical. Recognition of the uncertainty inherent in the benefit of immune and targeted therapies in a constructive manner may facilitate more timely and effective care-planning conversations between patients, carers and medical specialists.

Resistance mechanisms and cross-resistance for a pyridine-pyrimidine amide inhibitor of microtubule polymerization.

Despite their clinical importance, drug resistance remains problematic for microtubule targeting drugs. D4-9-31, a novel microtubule destabilizing agent, has pharmacology that suggests it can overcome common resistance mechanisms and has been shown to remain efficacious in cell and animal models with acquired taxane resistance. To better understand resistance mechanisms and the breadth of cross-resistance with D4-9-31, this study examines the A2780 ovarian cancer cell line as it develops acquired resistance with continuous exposure to D4-9-31. Analyzing cellular responses to D4-9-31 reveals that D4-9-31 resistance is associated with increased mitochondrial respiration, but no cross-resistance to other microtubule targeting agents is observed. Sequencing of transcripts of parental cells and resistant counterparts reveals mutations and altered expression of microtubule-associated genes, but not in genes commonly associated with resistance to microtubule targeting drugs. Additionally, our findings suggest distinct mechanisms drive short- and long-term drug resistance.

Effect of an acute exercise bout on immediate post-exercise irisin concentration in adults: A meta-analysis.

Irisin is a recently discovered myokine that increases adipocyte metabolism, induces further "browning" of white adipose tissue, and enhances glucose metabolism. No study has ever determined how an acute bout of exercise impacts immediate post-exercise irisin concentration using a meta-analytic approach. The purpose of this study is to determine the impact of an acute bout of exercise on the magnitude of post-exercise irisin concentration in adults using meta-analytic procedures. Searches were performed on PubMed, EMBASE, CINAHL, PEDro, SCOPUS, and SPORTDiscus databases. Effect summaries were obtained using random-effects models. Random-effects single and multiple meta-regressions were performed to determine relationships between, and potential confounding effects of, variables of interest. Ten articles were retained for the final meta-analysis, producing 21 study estimates. An acute bout of exercise was accompanied by a post-exercise average increase in irisin concentration of 15.0 (95% CI: 10.8%-19.3%). There was no significant relationship between post-exercise irisin concentration and age, intensity of aerobic exercise, or type of exercise training session (resistance vs aerobic training). Fitness level and body mass index were identified as significant predictive variables for post-exercise irisin concentration. However, a multiple meta-regression model identified fitness level as the single best predictor, with being fit (21.1%±2.2%) associated with a nearly twofold increase in post-exercise irisin concentration, compared with being unfit (11.8%±2.1%). Immediately following an acute bout of exercise, irisin concentration increases substantially in adults, with fitness level as an important modifier for the effect.

Documenting the Growth of Ultrasound Research in Emergency Medicine Through a Bibliometric Analysis of Accepted Academic Conference Abstracts.

OBJECTIVES: Ultrasound (US) has become an indispensable skill for emergency physicians. Growth in the use of US in emergency medicine (EM) has been characterized by practice guidelines, education requirements, and the number of EM US practitioners. Our purpose was to further document the growth of EM US by profiling the breadth, depth, and quality of US-related research presented at EM's most prominent annual research conference: the Society for Academic Emergency Medicine Annual Meeting. METHODS: We reviewed published research abstracts from the annual Society for Academic Emergency Medicine conferences from 1999 to 2015. Abstracts related to US were identified and examined for the number of authors and rigor of the research design. Designs were categorized as experimental, quasiexperimental, and nonexperimental. Abstract submissions were analyzed by the average rate of change over time. RESULTS: From 1999 to 2015, we observed a 10.2% increase in the number of accepted abstracts related to US research. This rate compared to a 3.2% average rate of change for all abstracts in general. The number of unique authors engaged in US research increased at a rate of 26.6%. Of the 602 abstracts identified as US related, only 12% could be considered experimental research. CONCLUSIONS: We observed larger increases in the number of US-related research relative to the total number of abstracts presented at a national conference. The number of investigators engaging in this research has also steadily increased. The research design of these studies was found to be primarily quasiexperimental. To improve the quality of EM's use of point-of-care US, more rigorous research with experimental designs is needed.

A global survey of HIV-positive people's attitudes towards cure research.

OBJECTIVES: Involvement of people living with HIV (PLHIV) in the design of HIV cure studies is important, given the potential risks to participants. We present results of an international survey of PLHIV to define these issues and inform cure research. METHODS: PLHIV were recruited in June-November 2014 through HIV websites, advocacy forums, social media and 12 UK HIV clinics. The survey included questions concerning demographics, HIV disease history, the desirability of types of cure and the patient's willingness to accept potential toxicity and treatment interruption (TI). We examined factors associated with TI and willingness to accept substantial risks. RESULTS: A total of 982 PLHIV completed the survey; 87% were male, 79% white and 81% men who have sex with men (MSM). Fifty-one per cent were aged 25-44 years and 69% were UK residents. The median time since diagnosis was 7 years [interquartile range (IQR) 2-17 years]. Eighty-eight per cent were receiving antiretrovirals (91% reported undetectable viral load). Health/wellbeing improvements (96%) and an inability to transmit HIV (90%) were more desirable cure characteristics than testing HIV-negative (69%). Ninety-five per cent were interested in participating in cure studies, and 59% were willing to accept substantial risks. PLHIV with a low CD4 count [201-350 cells/µL vs. ≥ 350 cells/µL; odds ratio (OR) 2.11; 95% confidence interval (CI) 1.11-4.00] were more likely to accept risks, whereas those with limited knowledge of HIV treatments vs. excellent/good knowledge and those aged ≥ 65 years vs. 45-64 years were less likely to accept risks [OR 0.58 (95% CI 0.37-0.90) and OR 0.18 (95% CI 0.07-0.45), respectively]. TI was acceptable for 62% of participants, with the main concerns being becoming unwell (82%), becoming infectious (76%) and HIV spreading through the body (76%). CONCLUSIONS: Cure research was highly acceptable to the PLHIV surveyed. Most individuals would accept risks, including TI, even in the absence of personal benefit. An optimal cure would improve health and minimize onward transmission risk.

The impact of immunoglobulin in acute HIV infection on the HIV reservoir: a randomized controlled trial.

OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19). Blood samples were evaluated for viral reservoir, immune activation, immune exhaustion and microbial translocation. Flexible sigmoidoscopy was performed at weeks 19, 24 and 48, and gut proviral DNA and cell numbers determined. RESULTS: IVIG was well tolerated and no viral blips (> 50 HIV-1 RNA copies/mL) occurred during IVIG therapy. From baseline to week 48, total HIV DNA in peripheral blood mononuclear cells (PBMCs) (cases: -3.7 log10 copies/106 CD4 cells; controls: -3.87 log10 copies/106 CD4 cells) declined with no differences observed between the groups (P = 0.49). Declines were observed in both groups from week 19 to week 48 in total HIV DNA in PBMCs (P = 0.38), serum low copy RNA (P = 0.57) and gut total HIV DNA (P = 0.55), but again there were no significant differences between arms. Biomarkers of immune activation, immune exhaustion and microbial translocation and the CD4:CD8 ratio were similar between arms for all comparisons. CONCLUSIONS: Although safe, IVIG in AHI did not impact total HIV DNA, immune function or microbial translocation in peripheral blood or gut tissue.

Metabolism and disposition of the anticancer quinolone derivative vosaroxin, a novel inhibitor of topoisomerase II.

Background Vosaroxin is a first-in-class anticancer quinolone derivative that is being investigated for patients with relapsed or refractory acute myeloid leukemia (AML). The primary objective of this study was to quantitatively determine the pharmacokinetics of vosaroxin and its metabolites in patients with advanced solid tumors. Methods This mass balance study investigated the pharmacokinetics (distribution, metabolism, and excretion) of vosaroxin in cancer patients after a single dose of 60 mg/m2 14C-vosaroxin, administered as short intravenous injection. Blood, urine and feces were collected over 168 h after injection or until recovered radioactivity over 24 h was less than 1% of the administered dose (whichever was earlier). Total radioactivity (TRA), vosaroxin and metabolites were studied in all matrices. Results Unchanged vosaroxin was the major species identified in plasma, urine, and feces. N-desmethylvosaroxin was the only circulating metabolite detected in plasma, accounting for <3% of the administered dose. However, in plasma, the combined vosaroxin + N-desmethylvosaroxin AUC0-∞ was 21% lower than the TRA AUC0-∞ , suggesting the possible formation of protein bound metabolites after 48 h when the concentration-time profiles diverged. The mean recovery of TRA in excreta was 81.3% of the total administered dose; 53.1% was excreted through feces and 28.2% through urine. Conclusions Unchanged vosaroxin was the major compound found in the excreta, although 10 minor metabolites were detected. The biotransformation reactions were demethylation, hydrogenation, decarboxylation and phase II conjugation including glucuronidation.

Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients.

Study question: Can a counseling tool be developed for women desiring elective oocyte cryopreservation to predict the likelihood of live birth based on age and number of oocytes frozen? Summary answer: Using data from ICSI cycles of a population of women with uncompromised ovarian reserve, an evidence-based counseling tool was created to guide women and their physicians regarding the number of oocytes needed to freeze for future family-building goals. What is known already: Elective oocyte cryopreservation is increasing in popularity as more women delay family building. By undertaking elective oocyte freezing at a younger age, women hope to optimize their likelihood of successful live birth(s) using their thawed oocytes at a future date. Questions often arise in clinical practice regarding the number of cryopreserved oocytes sufficient to achieve live birth(s) and whether or not additional stimulation cycles are likely to result in a meaningful increase in the likelihood of live birth. As relatively few women who have electively cryopreserved oocytes have returned to use them, available data for counseling patients wishing to undergo fertility preservation are limited. Study design, size, duration: A model was developed to determine the proportion of mature oocytes that fertilize and then form blastocysts as a function of age, using women with presumably normal ovarian reserve based on standard testing who underwent ICSI cycles in our program from January, 2011 through March, 2015 (n = 520). These included couples diagnosed exclusively with male-factor and/or tubal-factor infertility, as well as cycles utilizing egg donation. Age-specific probabilities of euploidy were estimated from 14 500 PGS embryo results from an external testing laboratory. Assuming survival of thawed oocytes at 95% for women <36 y and for egg donors, and 85% for women ≥36 y, and 60% live birth rate per transferred euploid blastocyst, probabilities of having at least one, two or three live birth(s) were calculated. Participants/materials, setting, method: First fresh male-factor and/or tubal-factor only autologous ICSI cycles (n = 466) were analyzed using Poisson regression to calculate the probability that a mature oocyte will become a blastocyst based on age. Egg donation cycles (n = 54) were analyzed and incorporated into the model separately. The proportion of blastocysts expected to be euploid was determined using PGS results of embryos analyzed via array comparative genomic hybridization. A counseling tool was developed to predict the likelihood of live birth, based on individual patient age and number of mature oocytes. Main results and the role of chance: This study provides an evidence-based model to predict the probability of a woman having at least one, two or three live birth(s) based on her age at egg retrieval and the number of mature oocytes frozen. The model is derived from a surrogate population of ICSI patients with uncompromised ovarian reserve. A user-friendly counseling tool was designed using the model to help guide physicians and patients. LIMITATIONS, REASONS FOR CAUTION: The data used to develop the prediction model are, of necessity, retrospective and not based on patients who have returned to use their cryopreserved oocytes. The assumptions used to create the model, albeit reasonable and data-driven, vary by study and will likely vary by center. Centers are therefore encouraged to consider their own blastocyst formation and thaw survival rates when counseling patients. Limitations, reasons for caution: Our model will provide a counseling resource that may help inform women desiring elective fertility preservation regarding their likelihood of live birth(s), how many cycles to undergo, and when additional cycles would bring diminishing returns. Study funding/competing interests: None. Trial registration number: Not applicable.

Hypertrophic Cardiomyopathy in Youth Athletes: Successful Screening With Point-of-Care Ultrasound by Medical Students.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is a life-threatening genetic cardiovascular disease that often goes undetected in young athletes. Neither history nor physical examination are reliable to identify those at risk. The objective of this study is to determine whether minimally trained medical student volunteers can use ultrasound to screen for HCM. METHODS: This was a prospective enrollment of young athletes performed at 12 area high schools and three area colleges, between May 2012 and August 2013. All participants underwent point-of-care ultrasound performed screening for HCM by trained medical students and reviewed by a pediatric cardiologist. An interventricular septum to left ventricular posterior wall ratio greater than 1.25 was considered to be abnormal (positive screen). RESULTS: A total of 2332 participants were enrolled. There were 137 (5.8%) with a positive screening for HCM, of which 7 (5.1%) were confirmed to have HCM by a pediatric cardiologist. In a small cohort with positive screen for HCM, there was a 100% sensitivity (95% confidence interval, 59.04 to 100%) and 4.86% (95% confidence interval, 1.98 to 9.76%) positive predictive value of for having HCM. CONCLUSIONS: Volunteer medical students, using point-of-care ultrasound, were able to effectively screen for HCM in young athletes.

Comparing Point-of-care-ultrasound (POCUS) to MRI for the Diagnosis of Medial Compartment Knee Injuries.

BACKGROUND: Ultrasound has become an increasingly utilized tool for the imaging of the musculoskeletal system, especially for imaging the components of the knee. Even though MRI is touted as being the golden standard for identifying knee pathologies, the use of ultrasound has gained popularity in this field given its ability for rapid diagnosis. This study aims to investigate the efficacy of point-of-care ultrasound (POCUS) to diagnose injuries to the medial knee compartment when compared to magnetic resonance imaging (MRI). METHODS: This was a prospective, observational study conducted at an orthopedic outpatient clinic. Prospective patients with medial knee pain scheduled for an MRI of the knee were evaluated by POCUS prior to the MRI. Sonographic findings were then compared to MRI results to assess correlation. RESULTS: Nine patients were enrolled in the study. Median age was 53 years and eight were male (89%). POCUS demonstrated 100% sensitivity and 50% specificity for medial meniscus tear and 67% sensitivity and 83% specificity for medial collateral ligament (MCL) tear. CONCLUSION: Ultrasound may have a role as the initial rapid imaging modality in patients with suspected medial meniscus or MCL tears as it is highly sensitive, and it may serve as an effective screening tool for patients with both acute and chronic knee pain.

Helicobacter saguini, a Novel Helicobacter Isolated from Cotton-Top Tamarins with Ulcerative Colitis, Has Proinflammatory Properties and Induces Typhlocolitis and Dysplasia in Gnotobiotic IL-10-/- Mice.

A urease-negative, fusiform, novel bacterium named Helicobacter saguini was isolated from the intestines and feces of cotton-top tamarins (CTTs) with chronic colitis. Helicobacter sp. was detected in 69% of feces or intestinal samples from 116 CTTs. The draft genome sequence, obtained by Illumina MiSeq sequencing, for H. saguini isolate MIT 97-6194-5, consisting of ∼2.9 Mb with a G+C content of 35% and 2,704 genes, was annotated using the NCBI Prokaryotic Genomes Automatic Annotation Pipeline. H. saguini contains homologous genes of known virulence factors found in other enterohepatic helicobacter species (EHS) and H. pylori These include flagellin, γ-glutamyl transpeptidase (ggt), collagenase, the secreted serine protease htrA, and components of a type VI secretion system, but the genome does not harbor genes for cytolethal distending toxin (cdt). H. saguini MIT 97-6194-5 induced significant levels of interleukin-8 (IL-8) in HT-29 cell culture supernatants by 4 h, which increased through 24 h. mRNAs for the proinflammatory cytokines IL-1ß, tumor necrosis factor alpha (TNF-α), IL-10, and IL-6 and the chemokine CXCL1 were upregulated in cocultured HT-29 cells at 4 h compared to levels in control cells. At 3 months postinfection, all H. saguini-monoassociated gnotobiotic C57BL/129 IL-10(-/-) mice were colonized and had seroconverted to H. saguini antigen with a significant Th1-associated increase in IgG2c (P < 0.0001). H. saguini induced a significant typhlocolitis, associated epithelial defects, mucosa-associated lymphoid tissue (MALT) hyperplasia, and dysplasia. Inflammatory cytokines IL-22, IL-17a, IL-1ß, gamma interferon (IFN-γ), and TNF-α, as well as inducible nitric oxide synthase (iNOS) were significantly upregulated in the cecal tissues of infected mice. The expression of the DNA damage response molecule γ-H2AX was significantly higher in the ceca of H. saguini-infected gnotobiotic mice than in the controls. This model using a nonhuman primate Helicobacter sp. can be used to study the pathogenic potential of EHS isolated from primates with naturally occurring inflammatory bowel disease (IBD) and colon cancer.

Prospective Assessment of Radiation in Pediatric Urology: The Pediatric Urology Radiation Safety Evaluation Study.

PURPOSE: Pediatric tissues are exquisitely sensitive to ionizing radiation from diagnostic studies and therapies involving fluoroscopy. We prospectively monitored radiation exposure in our pediatric urology patients during fluoroscopy guided operative procedures with single point dosimeters to quantify radiation dose. MATERIALS AND METHODS: Children undergoing fluoroscopy guided urological procedures were prospectively enrolled in the study from 2013 to 2015. Single point dosimeters were affixed to skin overlying the procedural site for the durations of the procedures to record dosimetry data. Patient demographics, procedural variables and fluoroscopic settings were recorded. RESULTS: A total of 78 patients underwent 96 procedures, including retrograde pyelography, ureteral stent insertion, ureteroscopy and percutaneous nephrolithotomy. Median patient age was 12 years (range 0.3 to 17) and median body mass index percentile for age was 70.7 (1.0 to 99.1). Median skin entrance radiation dose for all procedures performed was 0.56 mGy. Median dosages associated with the 29 diagnostic procedures and 49 definitive interventions were 0.6 mGy (mean 0.8, range 0.1 to 2.2) and 0.7 mGy (1.1, 0.0 to 5.5), respectively. The dose associated with the 18 procedures of temporization was significantly higher by comparison (median 1.0 mGy, mean 2.6, range 0.1 to 10.7, p = 0.02). CONCLUSIONS: Pediatric radiation exposure is not insignificant during urological procedures. Further multi-institutional work would provide context for our findings. Protocols to optimize fluoroscopic settings and minimize patient exposure, and guidelines for radiation based imaging should have a key role in all pediatric radiation safety initiatives.

Incorporating HIV/hepatitis B virus/hepatitis C virus combined testing into routine blood tests in nine UK Emergency Departments: the "Going Viral" campaign.

OBJECTIVES: Routine HIV screening is recommended in those UK hospitals and primary care settings where the HIV prevalence is > 0.2%. For hepatitis B virus (HBV) and hepatitis C virus (HCV), however, testing is targeted at at-risk groups. We investigated the prevalence of these blood-borne viruses (BBVs) during a routine testing pilot in UK Emergency Departments (EDs). METHODS: During the "Going Viral" campaign (13-19 October 2014), nine UK EDs in areas of high HIV prevalence offered routine tests for HIV, HBV and HCV to adults having blood taken as part of routine care. Patients who tested positive were linked to care. RESULTS: A total of 7807 patients had blood taken during their ED visit; of these, 2118 (27%) were tested for BBVs (range 9-65%). Seventy-one BBV tests were positive (3.4%) with 32 (45.1%) new diagnoses. There were 39 HCV infections (15 newly diagnosed), 17 HIV infections (six newly diagnosed), and 15 HBV infections (11 newly diagnosed). Those aged 25-54 years had the highest prevalence: 2.46% for HCV, 1.36% for HIV and 1.09% for HBV. Assuming the cost per diagnosis is £7, the cost per new case detected would be £988 for HCV, £1351 for HBV and £2478 for HIV. CONCLUSIONS: In the first study in the UK to report prospectively on BBV prevalence in the ED, we identified a high number of new viral hepatitis diagnoses, especially hepatitis C, in addition to the HIV diagnoses. Testing for HIV alone would have missed 54 viral hepatitis diagnoses (26 new), supporting further evaluation of routine BBV testing in UK EDs.