A patient with anaphylaxis to diphenhydramine without cross-reactivity to loratadine

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Application of Bayesian Belief Network for Agile Kanban Backlog Estimation

What is Agile Kanban? Different from Kanban for JIT manufacturing! Visualization of workflow Limit work in process (WIP

A joint analysis of influenza-associated hospitalizations and mortality in Hong Kong, 1998-2013.

Influenza viruses may cause severe human infections leading to hospitalization or death. Linear regression models were fitted to population-based data on hospitalizations and deaths. Surveillance data on influenza virus activity permitted inference on influenza-associated hospitalizations and deaths. The ratios of these estimates were used as a potential indicator of severity. Influenza was associated with 431 (95% CrI: 358-503) respiratory deaths and 12,700 (95% CrI: 11,700-13,700) respiratory hospitalizations per year. Majority of the excess deaths occurred in persons ≥65 y of age. The ratios of deaths to hospitalizations in adults ≥65 y were significantly higher for influenza A(H1N1) and A(H1N1)pdm09 compared to A(H3N2) and B. Substantial disease burden associated with influenza viruses were estimated in Hong Kong particularly among children and elderly in 1998-2013. Infections with influenza A(H1N1) was suggested to be more serious than A(H3N2) in older adults

Neural Responses to Peer Rejection in Anxious Adolescents: Contributions from the Amygdala-Hippocampal Complex

Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and 12 age-, gender- and IQ-matched, psychiatrically-healthy adolescents received ‘not interested’ and ‘interested’ feedback from unknown peers during a Chatroom task administered in a neuroimaging scanner. No group differences emerged in subjective ratings to peer feedback, but all participants reported more negative emotion at being rejected (than accepted) by peers to whom they had assigned high desirability ratings. Further highlighting the salience of such feedback, all adolescents, independent of anxiety levels, manifested elevated responses in the amygdala-hippocampal complex bilaterally, during the anticipation of feedback. However, anxious adolescents differed from healthy adolescents in their patterns of persistent amygdala-hippocampal activation following rejection. These data carry interesting implications for using neuroimaging data to inform psychotherapeutic approaches to social anxiety

The economic burden of influenza-associated outpatient visits and hospitalizations in China: a retrospective survey.

BACKGROUND: The seasonal influenza vaccine coverage rate in China is only 1.9 %. There is no information available on the economic burden of influenza-associated outpatient visits and hospitalizations at the national level, even though this kind of information is important for informing national-level immunization policy decision-making. METHODS: A retrospective telephone survey was conducted in 2013/14 to estimate the direct and indirect costs of seasonal influenza-associated outpatient visits and hospitalizations from a societal perspective. Study participants were laboratory-confirmed cases registered in the National Influenza-like Illness Surveillance Network and Severe Acute Respiratory Infections Sentinel Surveillance Network in China in 2013. Patient-reported costs from the survey were validated by a review of hospital accounts for a small sample of the inpatients. RESULTS: The study enrolled 529 outpatients (median age: eight years; interquartile range [IQR]: five to 20 years) and 254 inpatients (median age: four years; IQR: two to seven years). Among the outpatients, 22.1 % (117/529) had underlying diseases and among the inpatients, 52.8 % (134/254) had underlying diseases. The average total costs related to influenza-associated outpatient visits and inpatient visits were US$155 (standard deviation, SD US$ 122) and US$1,511 (SD US$ 1,465), respectively. Direct medical costs accounted for 45 and 69 % of the total costs related to influenza-associated outpatient and inpatient visits, respectively. For influenza outpatients, the mean cost per episode in children aged below five years (US$196) was higher than that in other age groups (US$ 129-153). For influenza inpatients, the mean cost per episode in adults aged over 60 years (US$2,735) was much higher than that in those aged below 60 years (US$ 1,417-1,621). Patients with underlying medical conditions had higher costs per episode than patients without underlying medical conditions (outpatients: US$186 vs. US$ 146; inpatients: US$1,800 vs. US$ 1,189). In the baseline analysis, inpatients reported costs were 18 % higher than those found in the accounts review (n = 38). CONCLUSION: The economic burden of influenza-associated outpatient and inpatient visits in China is substantial, particularly for young children, the elderly, and patients with underlying medical conditions. More widespread influenza vaccination would likely alleviate the economic burden of patients. The actual impact and cost-effectiveness analysis of the influenza immunization program in China merits further investigation

Common and specific amygdala-function perturbations in 2 depressed versus anxious adolescents

Context: Few studies directly compare amygdala function in depressive and anxiety disorders. 43 Data from longitudinal research emphasize the need for such studies in adolescents. 44 Objective: To compare amygdala response to varying attention and emotion conditions among 45 adolescents with Major Depressive Disorder (MDD) or anxiety disorders, relative to adolescents 46 with no psychopathology. 47 Design: Case-Control-Study. 48 Setting: Government Clinical Research Institute. 49 Participants: Eighty-seven adolescents matched on age, gender, intelligence, and social class: 26 50 with Major Depressive Disorder (MDD; 14 with and 12 without anxiety disorders), 16 with 51 anxiety disorders but no depression, and 45 with no psychopathology. 52 Main Outcome Measures: Blood oxygenated level dependent signal in the amygdala, measured 53 using event-related functional magnetic resonance imaging. During imaging, participants viewed 54 facial expressions (neutral, fearful, angry, happy) while attention was constrained (afraid, 55 hostility, nose width ratings) or unconstrained (passive-viewing). 56 Results: Left and right amygdala activation differed as a function of diagnosis, facial expression, 57 and attention-condition both when comorbid MDD/anxiety patients were included and excluded 58 (group-by-emotion-by-attention interactions: p-values≤.03). Focusing on fearful-face-viewing 59 events, anxiety and MDD patients both differed in amygdala responses from healthy participants 60 and from each other during passive-viewing. However, both MDD and anxiety patients, relative 61 to healthy participants, exhibited similar signs of amygdala hyper-activation to fearful faces when 62 rating subjectively experienced fear. 63 Conclusions: Adolescent MDD and anxiety disorders exhibit common and distinct functional 64 neural correlates during face processing. Attention modulates the degree to which common or 65 distinct amygdala perturbations manifest in these patient groups, relative to healthy peers

SARS Transmission among Hospital Workers in Hong Kong

Despite infection control measures, breakthrough transmission of severe acute respiratory syndrome (SARS) occurred for many hospital workers in Hong Kong. We conducted a case-control study of 72 hospital workers with SARS and 144 matched controls. Inconsistent use of goggles, gowns, gloves, and caps was associated with a higher risk for SARS infection (unadjusted odds ratio 2.42 to 20.54, p < 0.05). The likelihood of SARS infection was strongly associated with the amount of personal protection equipment perceived to be inadequate, having <2 hours of infection control training, and not understanding infection control procedures. No significant differences existed between the case and control groups in the proportion of workers who performed high-risk procedures, reported minor protection equipment problems, or had social contact with SARS-infected persons. Perceived inadequacy of personal protection equipment supply, infection control training <2 hours, and inconsistent use of personal protection equipment when in contact with SARS patients were significant independent risk factors for SARS infection

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471