Comparison of two continuous nebulized albuterol doses in critically ill children with status asthmaticus.

Objectives: Continuous nebulized albuterol is frequently used to treat children with status asthmaticus in the pediatric intensive care unit (PICU) but can have cardiovascular side effects. Limited data exist comparing different dosages. The purpose of this study was to compare hemodynamic side effects of two continuous albuterol doses (10 vs. 25 mg/h). Our hypothesis was that lower dose albuterol would be associated with lower toxicity without increased need for adjunctive therapies.Methods: We conducted a retrospective cohort study of all children over 2 years old receiving continuous nebulized albuterol for status asthmaticus in our PICU from 2011 to 2013. Standard initial therapy was intravenous steroids and continuous nebulized albuterol. Patients receiving 10 mg/h albuterol were compared to those receiving 25 mg/h. Clinical outcomes, including the need for additional asthma therapies as well as hypotension requiring fluid resuscitation, were evaluated.Results: About 632 patients were studied (342 received 10 mg/h, 290 received 25 mg/h). Children in the lower-dose group received less fluid resuscitation without increased adjunctive therapies when adjusted for confounders. Those in the 25 mg/h group receiving 17% higher bolus volume. Those receiving lower-dose albuterol had shorter adjusted PICU and hospital lengths of stay.Conclusions: In our PICU cohort of children with status asthmaticus, use of 10 mg/h continuous albuterol was associated with lower fluid bolus resuscitation without more adjunctive therapies. These findings support the safety of lower doses in this population. Prospective studies evaluating the efficacy and toxicity of specific continuous albuterol dosages in critically ill children with status asthmaticus are warranted.

HCV treatment barriers among HIV/HCV co-infected patients in the US: a qualitative study to understand low uptake among marginalized populations in the DAA era.

BACKGROUND: Well-tolerated, highly effective HCV treatment, known as direct-acting antivirals (DAAs), is now recommended for all people living with HCV, providing the tools for HCV elimination. We sought to understand treatment barriers among low-income HIV/HCV coinfected patients and providers with the goal of increasing uptake. METHODS: In 2014, we conducted 26 interviews with HIV/HCV co-infected patients and providers from a San Francisco clinic serving underinsured and publically-insured persons to explore barriers impacting treatment engagement and completion. Interview transcripts were coded, and a thematic analysis was conducted to identify emerging patterns. RESULTS: Conditions of poverty-specifically, meeting basic needs for food, shelter, and safety-undermined patient perceptions of self-efficacy to successfully complete HCV treatment programs. While patient participants expressed interest in HCV treatment, the perceived burden of taking daily medications without strong social support was an added challenge. This need for support contradicted provider assumptions that, due to the shorter-course regimens, support is unnecessary in the DAA era. CONCLUSIONS: Interferon-free treatments alone are not sufficient to overcome social-structural barriers to HCV treatment and care among low-income HIV/HCV co-infected patients. Support for patients with unmet social needs may facilitate treatment initiation and completion, particularly among those in challenging socioeconomic situations.

Diverse origins of hepatitis C virus in HIV co-infected men who have sex with men in Hong Kong.

BACKGROUND: Worldwide, Hepatitis C (HCV) infection has been increasingly recognized in HIV-positive men who have sex with men (MSM). The objective of this study was to characterize the transmission dynamics of acute HCV infection in HIV-positive MSM in Hong Kong using a molecular approach. FINDINGS: We retrospectively examined 24 HIV-positive MSM with acute HCV infection diagnosed between 2009 and 2014 in Hong Kong. Detection and molecular characterization of HCV was successfully performed in 22 (91.7 %) patients. Genotype 3a was the most prevalent as identified in 14 (63.6 %) MSM, followed by 1a in 4 (18.2 %), 6a in 2 (9.1 %), and 1each (4.5 %) for 1b and 2a. The high prevalence of genotype 3a in MSM was in stark contrast to its rarity among HCV infected injection drug users (IDU) in Hong Kong. Phylogenetic analyses revealed a monophyletic HCV-3a cluster composing of MSM without injection history, and a homologous pair with HCV-6a genotype. There was otherwise no temporal or genetic clustering of the corresponding HIV sequences. CONCLUSIONS: The origin of sexually acquired acute HCV infections in HIV-positive MSM was diverse and not directly linked with local IDU. The transmission dynamics of HIV and HCV infections in MSM in Hong Kong were evidently unrelated.

Epidemiology of sexually transmitted viral hepatitis in human immunodeficiency virus-positive men who have sex with men in Asia.

Both human immunodeficiency virus (HIV) and viral hepatitis constitute major disease burden globally. As with other parts of the world, the HIV epidemic in Asia impacts mainly on men who have sex with men, one of the at-risk populations for sexually transmitted viral hepatitis. With the increasing availability of effective antiretroviral therapy, HIV-related mortality of people living with HIV has markedly reduced. Liver disease has become an important cause of mortality and morbidity in the HIV-infected population. With the improvement of socioeconomic conditions and availability of healthcare in Asian countries in recent years, the epidemiology of sexually transmitted viral hepatitis among HIV-positive men who have sex with men has also evolved. This review updates the epidemiology of different types of sexually transmitted viral hepatitis in this defined population in Asia.

Accelerating prevention of mother-to-child transmission of HIV: ten-year experience of universal antenatal HIV testing programme in a low HIV prevalence setting in Hong Kong.

Hong Kong has a low prevalence of HIV infection at less than 0.01%. Universal Antenatal HIV Testing Programme (UATP) was launched in all public antenatal units in September 2001. In 2008, voluntary rapid HIV testing was introduced in all public labour units to fill up the gap for pregnant women without HIV testing during the antenatal period. This study evaluated the performance of UATP and rapid HIV testing with indicators. From September 2001 to December 2011, process and outcome indicators for monitoring and evaluation were collected from the service providers in the form of monthly return of workload statistics and case-based statistics of each identified HIV-positive pregnancy via reporting forms. A total of 479,160 antenatal HIV tests and 2,675 rapid tests were performed in the study period. The acceptance rate for UATP and rapid HIV testing was 98% and 80.4% respectively. With the implementation of rapid HIV testing in January 2008, the proportion of pregnant women with HIV status discerned before delivery increased from 84.9% in 2006 to over 99.5% since 2008. The HIV prevalence in UATP and rapid HIV testing was 0.02% and 0.1% respectively. Fifty-three (68%) out of 78 HIV-infected pregnant women identified from the programme have delivered locally. Forty-three (81%) of them delivered by caesarean section and 50 (94%) of them were given antiretrovirals for intervention. Only three children born before the implementation of rapid HIV testing were HIV-infected. In conclusion, UATP and its rapid HIV testing component have been highly accepted and effective in the prevention of perinatal HIV transmission in Hong Kong.

A microglia-containing cerebral organoid model to study early life immune challenges.

Prenatal infections and activation of the maternal immune system have been proposed to contribute to causing neurodevelopmental disorders (NDDs), chronic conditions often linked to brain abnormalities. Microglia are the resident immune cells of the brain and play a key role in neurodevelopment. Disruption of microglial functions can lead to brain abnormalities and increase the risk of developing NDDs. How the maternal as well as the fetal immune system affect human neurodevelopment and contribute to NDDs remains unclear. An important reason for this knowledge gap is the fact that the impact of exposure to prenatal risk factors has been challenging to study in the human context. Here, we characterized a model of cerebral organoids (CO) with integrated microglia (COiMg). These organoids express typical microglial markers and respond to inflammatory stimuli. The presence of microglia influences cerebral organoid development, including cell density and neural differentiation, and regulates the expression of several ciliated mesenchymal cell markers. Moreover, COiMg and organoids without microglia show similar but also distinct responses to inflammatory stimuli. Additionally, IFN-γ induced significant transcriptional and structural changes in the cerebral organoids, that appear to be regulated by the presence of microglia. Specifically, interferon-gamma (IFN-γ) was found to alter the expression of genes linked to autism. This model provides a valuable tool to study how inflammatory perturbations and microglial presence affect neurodevelopmental processes.

Multidisciplinary quality improvement initiative to reduce ventilator-associated tracheobronchitis in the PICU.

OBJECTIVE: To test the hypothesis that successful implementation of a care bundle designed to prevent nosocomial airway infection will be associated with decreased incidence of ventilator-associated tracheobronchitis. DESIGN: Prospective pre- and post interventional. SETTING: PICU at an academic medical center PATIENTS: : All patients admitted to the PICU who received invasive mechanical ventilation for greater than or equal to 48 hours between March 1, 2009, and December 31, 2011. INTERVENTION: Multidisciplinary, unit wide implementation of an evidence-based care bundle to prevent ventilator-associated airway infection. MEASUREMENTS AND MAIN RESULTS: There were 725 patients included in the analysis (338 patients preintervention and 387 patients postintervention). Baseline ventilator-associated tracheobronchitis rate in the preintervention period was 3.9 cases per 1,000 ventilator days compared with 1.8 cases per 1,000 ventilator days postintervention (p = 0.04, Fisher exact test). Compared with patients without ventilator-associated tracheobronchitis or ventilator-associated pneumonia, patients with ventilator-associated tracheobronchitis had fewer ventilator-free days in 28 days (4.9 vs 22; p < 0.0001, Mann-Whitney U test) and fewer ICU-free days in 28 days (0.5 vs 19; p < 0.0001, Mann-Whitney U test). These relationships remained significant after adjusting for covariates by multivariable linear regression. CONCLUSIONS: Successful implementation of a care bundle to prevent ventilator-associated infection was associated with decreased incidence of ventilator-associated tracheobronchitis. Development of ventilator-associated tracheobronchitis was independently associated with adverse outcomes in our cohort of pediatric ICU patients.

Postpyloric feeding tube placement at the bedside: Complication rate and impact on length of stay.

BACKGROUND: Postpyloric feeding tube (PPFT) placement is essential for the ongoing nutrition care of critically ill children requiring noninvasive and invasive ventilation. PPFTs are placed by a variety of providers, including advanced practice nurses (APNs), surgeons, gastroenterologists, and radiologists. Complication rates, time to enteral nutrition (EN) following placement, and association with length of stay (LOS) have not been well documented. METHODS: A query of the electronic medical record identified patients in the pediatric intensive care unit (PICU) in whom PPFTs were placed. A retrospective chart review was performed to identify patient demographics; PPFT placement provider, indication, and duration; PICU LOS; hospital LOS; and patient pediatric risk of mortality (PRISM) scores. RESULTS: A total of 452 PPFTs were placed in 346 patients , with 318 placed by APNs. There was only one complication in 452 placed PPFTs. PRISM scores between patient groups for APN-placed PPFTs and non-APN-placed PPFTs were not significantly different. Mean time from hospital admission to PPFT placement was 1.5 days (APN) to 2.0 days (non-APN) (P < .02). Spearman correlation coefficients demonstrated shorter hospital and PICU LOS were associated with shorter duration to insertion. CONCLUSION: Overall complication rates of PPFT insertion is very low and do not significantly differ between provider type , even in patients with higher PRISM scores. Additionally, early time to insertion of PPFT is associated with decreased hospital and PICU LOS. Further research is needed to determine if the earlier time to insertion of PPFTs is associated with the achievement of goal feeds.

Fabrication of Spray-Dried Microcapsules Containing Noni Juice Using Blends of Maltodextrin and Gum Acacia: Physicochemical Properties of Powders and Bioaccessibility of Bioactives during In Vitro Digestion.

Microencapsulation of fermented noni juice (FNJ) into powder format could protect bioactive compounds, reduce the unpleasant odour and improve the acceptability for consumers. Blends of maltodextrin (MD) and gum acacia (GA) were used to achieve spray-drying microencapsulation of noni juice at different blending ratios. The physicochemical properties including microstructure, moisture content, water activity, particle size, bulk/tapped density, dissolution rate, ATR-FTIR and the bioaccessibility of bioactive compounds in powders during in vitro digestion were examined. Results showed that blends produced with more GA produced microcapsules with lower moisture content, water activity and bulk/tapped density, but slower powder dissolution. The ATR-FTIR results suggested that there were no significant chemical interactions between the core material and carrier or between the MD and GA in the blend powders. The spray-dried noni juice powder produced using the blends with higher ratio of GA to MD showed a better protection on the bioactive compounds, resulting in a higher bioaccessibility of powders during in vitro digestion. This study provides insights into microencapsulation of noni juice using blends of MD and GA and examines the physicochemical properties and bioaccessibilities of spray-dried powders as affected by the selected carriers.

Streptolysin S inhibits neutrophil recruitment during the early stages of Streptococcus pyogenes infection.

In contrast to infection of superficial tissues, Streptococcus pyogenes infection of deeper tissue can be associated with a significantly diminished inflammatory response, suggesting that this bacterium has the ability to both promote and suppress inflammation. To examine this, we analyzed the behavior of an S. pyogenes mutant deficient in expression of the cytolytic toxin streptolysin S (SLS-) and evaluated events that occur during the first few hours of infection by using several models including injection of zebrafish (adults, larvae, and embryos), a transepithelial polymorphonuclear leukocyte (PMN) migration assay, and two-photon microscopy of mice in vivo. In contrast to wild-type S. pyogenes, the SLS- mutant was associated with the robust recruitment of neutrophils and significantly reduced lethal myositis in adult zebrafish. Similarly, the mutant was attenuated in embryos in its ability to cause lethality. Infection of larva muscle allowed an analysis of inflammation in real time, which revealed that the mutant had recruited PMNs to the infection site. Analysis of transepithelial migration in vitro suggested that SLS inhibited the host cells' production of signals chemotactic for neutrophils, which contrasted with the proinflammatory effect of an unrelated cytolytic toxin, streptolysin O. Using two-photon microscopy of mice in vivo, we showed that the extravasation of neutrophils during infection with SLS- mutant bacteria was significantly accelerated compared to infection with wild-type S. pyogenes. Taken together, these data support a role for SLS in the inhibition of neutrophil recruitment during the early stages of S. pyogenes infection.

Clinical Decision Support Tools and a Standardized Order Set Enhances Early Enteral Nutrition in Critically Ill Children.

BACKGROUND: Critically ill children in a pediatric intensive care unit (PICU) have unique nutrition needs that are challenging to achieve and thus are at high risk of malnutrition. There is increasing evidence that children who reach caloric goals early have improved outcomes. The purpose of this initiative was to implement an enteral nutrition (EN) algorithm in a tertiary care PICU utilizing clinical decision support tools (CDSTs) and a standardized order set within an electronic health record. METHODS: A quality improvement initiative was undertaken to implement an EN feeding protocol using electronic CDSTs, including a new standardized order set. RESULTS: In a historical cohort of 376 patients, only 18% met goal EN in the first 48 hours of admission. The EN protocol was implemented in 272 patients who met 88% goal feed volume within 48 hours of intensive care unit admission. Median time to start EN (1.7 vs 1.3 days, P < 0.0001) and time to goal nutrition (2.8 vs 2.2 days, P < 0.001) improved after project implementation. Length of stay in the PICU was significantly reduced following protocol implementation (202 hours pre-implementation vs 156 hours post implementation, P < 0.0001). CONCLUSIONS: We used CDSTs and standardized order sets to implement a nutrition algorithm to facilitate and likely improve the nutrition care of critically ill children.

A longitudinal study on latent TB infection screening and its association with TB incidence in HIV patients.

Latent TB infection (LTBI) in HIV patients, its treatment, and immunological recovery following highly active antiretroviral therapy (HAART) could interact and impact TB disease progression. We aim to examine the factors associated with LTBI and TB disease development among HIV patients. Longitudinal clinical and laboratory data were accessed from the largest HIV specialist clinic in Hong Kong, where HAART and yearly LTBI screening are routinely provided for HIV patients. Between 2002 and mid-2017, among 2079 HIV patients with 14119 person-years (PY) of follow-up, 32% of LTBI screened patients (n = 1740) were tested positive. The overall TB incidence was 1.26/100 PY from HIV diagnosis to HAART initiation, falling to 0.37/100 PY. A lower risk of TB disease progression was associated with local residence, Chinese ethnicity, negative baseline LTBI result, being on HAART, LTBI treatment, higher baseline CD4 and CD4/CD8 ratio. A positive test at baseline, but not subsequent testing results, was significantly associated with TB disease development. Baseline LTBI screening is an important strategy for identifying HIV patients at risk of TB disease progression. Routine repeat LTBI screening on an annual basis might not give additional benefits to patients on HAART with good immunological responses. Such practice should require re-evaluation.

Latent Tuberculosis Infection Testing Strategies for HIV-Positive Individuals in Hong Kong.

Importance: With immune recovery following early initiation of antiretroviral therapy (ART), the risk of tuberculosis (TB) reactivation among individuals with HIV could be reduced. The current strategy of annual latent TB infection (LTBI) testing should be revisited to increase cost-effectiveness and reduce the intensity of testing for individuals. Objective: To analyze the cost-effectiveness of LTBI testing strategies for individuals in Hong Kong with HIV who had negative LTBI test results at baseline. Design, Setting, and Participants: This decision analytical model study using a cost-effectiveness analysis included 3130 individuals with HIV in Hong Kong, China, which has an intermediate TB burden and a low incidence of HIV-TB coinfection. A system dynamics model of individuals with HIV attending a major HIV specialist clinic in Hong Kong was developed and parameterized by longitudinal clinical and LTBI testing records of patients during a 15-year period. The study population was stratified by age group, CD4 lymphocyte level, ART status, and right of abode. Alternative strategies for LTBI testing after a baseline test were compared with annual testing under different coverages of ART, LTBI testing, and LTBI treatment scenarios in the model. An annual discounting rate of 3.5% was used in cost-effectiveness analysis. Main Outcomes and Measures: Proportion of new TB cases averted above base case scenario, discounted quality-adjusted life-years gained (QALYG), incremental cost, and incremental cost-effectiveness ratios in 2017 to 2023. Results: A total of 3130 patients with HIV (2740 [87.5%] male and 2800 [89.5%] younger than 50 years at HIV diagnosis) with 16 630 person-years of follow-up data from 2002 to 2017 were analyzed. Of these, 94 patients (0.67 [95% CI, 0.51-0.91] per 100 person-years) developed TB. Model estimates of cumulative number of TB cases would reach 146 by 2023, with the annual number of new TB diagnoses ranging from 6 to 8. For patients who had negative LTBI test results at baseline, subsequent LTBI testing strategies were ranked by ascending effectiveness as follows: (1) no testing, (2) test by risk factors, (3) biennial testing for all, (4) up to 3 tests for all, and (5) annual testing for all. Applying a willingness-to-pay threshold of $50 000 per QALYG, none of the subsequent testing strategies were cost-effective. Test by risk factors and up to 3 tests for all were cost-effective only if the willingness-to-pay threshold was increased to $100 000 per QALYG and $200 000 per QALYG, respectively. More new TB cases would be averted by expanding LTBI testing and/or treatment coverage. Conclusions and Relevance: Changing the current testing strategy to less intense testing strategies is likely to be cost-effective in the presence of an increased coverage of baseline LTBI testing and/or treatment.

The signal recognition particle pathway is required for virulence in Streptococcus pyogenes.

The signal recognition particle (SRP) pathway is a universally conserved pathway for targeting polypeptides for secretion via the cotranslational pathway. In particular, the SRP pathway is thought to be the main mechanism for targeting polypeptides in gram-positive bacteria, including a number of important human pathogens. Though widely considered to be an essential cellular component, recent advances have indicated this pathway may be dispensable in gram-positive bacteria of the genus Streptococcus under in vitro conditions. However, its importance for the pathogenesis of streptococcal disease is unknown. In this study, we investigated the importance of the SRP pathway for virulence factor secretion in the human pathogen Streptococcus pyogenes. While the SRP pathway was not found to be essential for viability in vitro, SRP mutants demonstrated a medium-specific growth defect that could be rescued by the addition of glucose. We also observed that a distinct subset of virulence factors were dependent upon the SRP pathway for secretion, whereas others were completely independent of this pathway. Significantly, deletion of the SRP pathway resulted in mutants that were highly attenuated in both a zebrafish model of necrotic myositis and a murine subcutaneous ulcer model, highlighting the importance of this pathway in vivo. These studies emphasize the importance of the SRP pathway for the in vivo survival and pathogenesis of S. pyogenes.

Surgical site abscess caused by Lactobacillus fermentum identified by 16S ribosomal RNA gene sequencing.

We report the first case of surgical site abscess caused by Lactobacillus fermentum from a 53-year-old woman with squamous cell carcinoma of the esophagus after transthoracic esophagectomy and neoadjuvant chemoirradiation. 16S rRNA gene sequencing is a useful tool to better characterize the epidemiology and clinical significance of L. fermentum.

Screening and treatment of latent tuberculosis infection among HIV-infected patients in resource-rich settings.

Current international guidelines recommend screening and treatment of latent tuberculosis (TB) infection in HIV-infected patients in all settings. The main factors affecting the risk of TB in HIV-infected patients include the level of immunosuppression, coverage of antiretroviral therapy and local TB burden. In resource-rich settings where antiretroviral therapy is more accessible and HIV-infected patients are expected to be diagnosed at an earlier stage, local TB burden remains a key factor on their risk of TB. This article reviewed the epidemiology of latent TB infection among the adult HIV-infected patients, and the use and benefit of screening and treatment of latent TB infection in resource-rich settings in the past decade. While such practice should be continued in countries with medium or high TB burden, targeted screening and treatment only for HIV-infected patients with additional risk factors for TB might be a more practical option in resource-rich countries with low TB burden.

Dexmedetomidine Infusion to Control Agitation due to Anticholinergic Toxidromes in Adolescents, a Case Series.

Dexmedetomidine is an α2-adrenergic agonist approved by the US Food and Drug Administration for the sedation of adults who are intubated on mechanical ventilation and in non-intubated adults who are undergoing surgical procedures. However, it has also recently become a commonly used sedative agent in varied clinical settings for the pediatric patient as well. We present the use of dexmedetomidine for sedation in a unique clinical scenario, the severely agitated and combative patient following the intentional misuse of anticholinergic drugs. Its applications in this situation are discussed, and previous reports in the literature are reviewed.

More safer sex intervention needed for HIV-positive MSM with higher education level for prevention of sexually transmitted hepatitis C.

INTRODUCTION: The epidemiology of hepatitis C virus (HCV) infections in Chinese HIV-infected men who have sex with men (MSM) remains obscure. More data is required to understand the epidemic and set up preventive strategy. MATERIALS AND METHODS: Baseline and annual testing of anti-HCV was in place for all HIV-infected MSM in the largest HIV clinic in Hong Kong. Logistic regression was used to compare those with HCV seroconversion (seroconverters) with those remained tested anti-HCV negative (non-seroconverters) to identify factors associated with incident HCV. RESULTS: From 1999 to 2013, 1311 patients were tested for anti-HCV seroconversion, contributing to 6295 patient-years of observation. Fourteen (1.1%) patients seroconverted, with genotype 3 being most commonly detected. The overall incidence rate of HCV infection was 0.22 per 100 patient-years (PY) in the cohort. The incidence rate increased from 0.13 per 100PY before 2002 to 0.19 per 100PY in 2002-2007 and 0.47 per 100PY in 2008-2013. All the seroconverters were Chinese, with median age of anti-HCV seroconversion at 38 years (range: 28-53 years). None of them were injecting drug users. As compared with the non-seroconverters, seroconverters were of higher education level (85.7% vs 50.7% tertiary education or above, OR 5.28, p=0.021) and had prior history of sexually transmitted infection (92.9% vs 60.9%, OR 8.34, p=0.041). More seroconverters were found to have history of syphilis infection (57.1% vs 37.2%, p=0.134) but the difference was not statistically significant. Baseline CD4 count and HIV viral load, proportion on antiretroviral therapy and duration of antiretroviral therapy were not different between two groups. CONCLUSIONS: The incidence of HCV has been increasing among HIV-infected MSM non-injecting drug users in Hong Kong. More education and intervention on safer sex is required to be targeted on those with higher education level.