Mechanism of Rhinovirus Immunity and Asthma.

The majority of asthma exacerbations in children are caused by Rhinovirus (RV), a positive sense single stranded RNA virus of the Picornavirus family. The host has developed virus defense mechanisms that are mediated by the upregulation of interferon-activated signaling. However, the virus evades the immune system by inducing immunosuppressive cytokines and surface molecules like programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on immunocompetent cells. Initially, RV infects epithelial cells, which constitute a physiologic mucosal barrier. Upon virus entrance, the host cell immediately recognizes viral components like dsRNA, ssRNA, viral glycoproteins or CpG-DNA by host pattern recognition receptors (PRRs). Activation of toll like receptors (TLR) 3, 7 and 8 within the endosome and through MDA-5 and RIG-I in the cytosol leads to the production of interferon (IFN) type I and other antiviral agents. Every cell type expresses IFNAR1/IFNAR2 receptors thus allowing a generalized antiviral activity of IFN type I resulting in the inhibition of viral replication in infected cells and preventing viral spread to non-infected cells. Among immune evasion mechanisms of the virus, there is downregulation of IFN type I and its receptor as well as induction of the immunosuppressive cytokine TGF-ß. TGF-ß promotes viral replication and is associated with induction of the immunosuppression signature markers LAP3, IDO and PD-L1. This article reviews the recent advances on the regulation of interferon type I expression in association with RV infection in asthmatics and the immunosuppression induced by the virus.

Threatening drug-drug interaction in a kidney transplant patient with coronavirus disease 2019 (COVID-19).

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy.

Development and Content Validity Testing of Patient-Reported Outcome Items for Children to Self-Assess Symptoms of the Common Cold.

BACKGROUND AND OBJECTIVE: No pediatric patient-reported outcome instruments specific to the common cold are found in the literature. This study involved development and content validity testing of patient-reported outcome items (questions and response options) assessing cold symptoms in children aged 6-11 years. METHODS: Draft patient-reported outcome instructions, items, response scales, and recall periods were developed based on the literature and existing measures. Qualitative interviews were conducted with children (n = 39) who were currently (n = 31) or had recently (n = 8) experienced a cold and ten parents of a subset of children aged 6-8 years. The interviews were conducted over two rounds and included open-ended concept elicitation questioning, a free-drawing task, a card sorting task, and a task involving circling parts of the body, followed by cognitive debriefing of draft items. Thematic analysis of verbatim transcripts was performed to analyze the qualitative data. The findings were used to support revisions to the draft patient-reported outcome. RESULTS: Ten symptom concepts were reported by the children during concept elicitation. The creative tasks helped the children to describe their symptoms, generally using consistent language to do so, irrespective of age. Nineteen patient-reported outcome items were developed and subject to cognitive debriefing. Debriefing with both children and parents informed several small revisions and provided evidence that the majority of children found most patient-reported outcome items easy to understand, and that the items were mainly interpreted consistently and as intended. CONCLUSIONS: This in-depth qualitative study has supported identification of relevant symptom concepts and the development and refinement of patient-reported outcome items to assess those concepts. The findings support the content validity of the items and suggest that they can be used with confidence in children aged 9 years and older. For children aged 6-8 years, it is recommended the items are administered with initial adult supervision to explain the more difficult concepts or through parent/interviewer administration.

Binafuxi granules in the treatment of common cold with heat syndrome based on traditional Uighur medicine: study protocol for a multicenter randomized controlled trial.

BACKGROUND: The common cold is a highly prevalent illness with significant impact on society and health care. Common cold with heat syndrome (CCHS) is one of the most common types based on syndrome differentiation by traditional Uighur medicine (TUM), which is widely used in Central Asia. The study is designed to explore the efficacy, safety and optimal therapeutic dosage of Binafuxi granules in treating CCHS. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Participants (n = 240) will be enrolled from five centers across China and randomly assigned to the high-dose group, low-dose group or placebo control group in a 1:1:1 ratio. All eligible patients will receive test drugs twice daily for 3 days. The primary outcome is the time to fever relief. Secondary outcomes include the time to fever clearance, duration of primary symptoms and each symptom and change in TUM symptom score. DISCUSSION: This is the first placebo-controlled randomized clinical trial of a Uighur medicine in treating common cold. It will provide robust evidence on the efficacy and safety of Binafuxi granules in the treatment of CCHS. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IIR-17013379 . Registered on 14 November 2017.

25-Hydroxyvitamin D variability within-person due to diurnal rhythm and illness: a case report.

BACKGROUND: Vitamin D nutrition research requires accurate measures of circulating 25-hydroxyvitamin D. Our objectives were to test whether a diurnal fluctuation in blood-spot concentrations of 25-hydroxyvitamin D can be demonstrated statistically in a single individual, and whether such fluctuation is affected by the pre-dose versus post-dose timing of the blood draw. CASE PRESENTATION: The participant in this case study was a generally healthy Caucasian woman in her 40s who has taken 5000 IU vitamin D3 supplement at midday for over 1 year. Each blood sample was drawn individually from a finger prick onto filter paper at morning, midday, or night, on 4 days (three groups of five individual blood samples per collection day). On days 1 and 2, the midday samples were collected approximately 1 hour after the supplement was taken; on days 3 and 4, the midday samples were collected within an hour prior to supplementation (the classical, daily "trough" value for a drug). There was a significant daily pattern of variation in 25-hydroxyvitamin D concentrations (analysis of variance p ≤ 0.02 for 3 of the 4 days): peak midday mean 25-hydroxyvitamin D was approximately 20% higher than in the morning, and approximately 13% higher than in the evening. Trough sampling produced no significant difference in 25-hydroxyvitamin D compared to sampling an hour after the dose. An incidental finding was that acute illness during the study was related to acutely lower 25-hydroxyvitamin D at every sampling time in the day (p < 0.00001). CONCLUSIONS: There was a consistent diurnal variation in 25-hydroxyvitamin D, with the peak at midday. There was no difference between trough versus post-dose blood draws. Acute illness may acutely lower serum 25-hydroxyvitamin D levels. Because within-person, within-day variability in 25-hydroxyvitamin D is approximately 20%, sampling time introduces systematic error in vitamin D nutritional assessment that is bigger than random analytical error or choice of assay method.

Association of Daily Workload, Wellness, and Injury and Illness During Tours in International Cricketers.

PURPOSE: To examine the relationship between player internal workloads, daily wellness monitoring, and injury and illness in a group of elite adolescent cricketers during overseas competitions. METHODS: A total of 39 male international adolescent cricketers (17.5 [0.8] y) took part in the study. Data were collected over 5 tours across a 3-y period (2014-2016). Measures of wellness were recorded and daily training loads were calculated using session rating of perceived exertion. The injury and illness status of each member of the squad was recorded daily. Acute and chronic workloads were calculated using 3-d and 14-d moving averages. Acute workloads, chronic workloads, and acute chronic workload ratios were independently modeled as fixed effects predictor variables. RESULTS: In the subsequent week, a high 3-d workload was significantly associated with an increased risk of injury (relative risk = 2.51; CI = 1.70-3.70). Similarly, a high 14-d workload was also associated with an increased risk of injury (relative risk = 1.48; CI = 1.01-2.70). Individual differences in the load-injury relationship were also found. No clear relationship between the acute chronic workload ratios and injury risk was found, but high chronic workloads combined with high or low acute chronic workload ratios showed an increased probability of injury compared with moderate chronic workloads. There were also trends for sleep quality and cold symptoms worsening the week before an injury occurred. CONCLUSION: Although there is significant individual variation, short-term high workloads and change in wellness status appear to be associated with injury risk.

Short-term repeated HRV-16 exposure results in an attenuated immune response in vivo in humans.

INTRODUCTION: Naturally, development of adaptive immunity following HRV infection affects the immune response. However, it is currently unclear whether or not HRV re-exposure within a short time frame leads to an altered innate immune response. The "experimental cold model" is used to investigate the pathogenesis of HRV infection and allows us to investigate the effects of repeated exposure on both local and systemic innate immunity. METHODS: 40 healthy male and female (1:1) subjects were nasally inoculated with HRV-16 or placebo. One week later, all subjects received HRV-16. Baseline seronegative subjects (n = 18) were included for further analysis. RESULTS: Infection rate was 82%. Primary HRV infection induced a marked increase in viral load and IP-10 levels in nasal wash, while a similar trend was observed for IL-6 and IL-10. Apart from an increase in IP-10 plasma levels, HRV infection did not induce systemic immune effects nor lower respiratory tract inflammation. With similar viral load present during the second HRV challenge, IP-10 and IL-6 in nasal wash showed no increase, but gradually declined, with a similar trend for IL-10. CONCLUSION: Upon a second HRV challenge one week after the first, a less pronounced response for several innate immune parameters is observed. This could be the result of immunological tolerance and possibly increases vulnerability towards secondary infections.

Associations of Serum 25(OH)D Concentrations with Lung Function, Airway Inflammation and Common Cold in the General Population.

Vitamin D is hypothesized to have a beneficial effect on lung function and respiratory infections. The aim of this study was to assess the relationship of serum 25-hydroxyvitamin D (25(OH)D) concentrations with lung function, airway inflammation and common colds. We performed a cross-sectional analysis in the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort study. We included participants with measurements of serum 25(OH)D, Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), Fractional Exhaled Nitric Oxide (FeNO), and data on self-reported common colds (n = 6138). In crude associations, serum 25(OH)D was positively associated with FEV1 and FVC, and negatively with FeNO and the occurrence of a common cold. After adjustment for confounders, however, these associations disappeared. Stratified analyses showed that Body Mass Index (BMI) was an effect modifier in the relationship between serum 25(OH)D and FEV1, FVC and FeNO. In obese participants (BMI ≥ 30 kg/m²), 10 nmol/L higher 25(OH)D was associated with 0.46% predicted higher FEV1 (95% Confidence Interval: 0.17 to 0.75), 0.46% predicted higher FVC (0.18 to 0.74), and 0.24 ppb lower FeNO (-0.43 to -0.04). Thus, in the total study population, 25(OH)D concentrations were not associated with lung function, airway inflammation and common colds. In obese participants, however, higher 25(OH)D concentrations were associated with a better lung function and lower airway inflammation.

Propolis nasal spray effectively improves recovery from infectious acute rhinitis and common cold symptoms in children: a pilot study.

Currently, treatment for acute rhinitis (AR) is symptomatic but no clear agreement exists to control its development. Propolis extract may appear as a promising natural treatment for AR, but its beneficial effects have not yet been fully tested. Forty children suffering from AR and common cold symptoms aged between 2-12 years were enrolled in a prospective epidemiological multicentre study. A 7-day treatment with propolis nasal spray (3 times/day) was applied and a comparison of symptomatology, subjective global improvement and quality of life (QoL) between baseline (day 1) and final (day 7) visits were performed. The main goal was to evaluate the changes in symptom intensity using the Jackson’s scoring test. After 7 days of treatment there was a significant decrease of symptoms both in the total score (p less than 0.0001) and in regard to each AR symptom (p less than 0.01). On the whole, the sample reported no symptoms by day 7, and the resolution of symptoms occurred approximately at day 4. Furthermore, there was no need for supplementary treatment. Both the subjective global improvement impression and the QoL of patients appeared to significantly improve after treatment. No adverse events (AEs) were found globally. It can be concluded that propolis nasal spray effectively improves recovery from infectious AR and common cold symptoms in children and is an optimal alternative in the treatment of this disease without need for any adjuvant treatment.

Comparison of the Benefit Feeling Rate Based on the Sho of OTC Kakkonto, Cold Remedy and Cold Remedy with Kakkonto Combination Product.

Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an OTC pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n=555), cold remedies with KK (CK, n=315), and general cold remedies (GC, n=539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.

Colds as predictors of the onset and severity of COPD exacerbations.

RATIONALE: Common colds are associated with acute respiratory symptom exacerbations in COPD patients. OBJECTIVE: To determine exacerbation risk and severity in COPD patients with/without coincident self-reported colds. METHODS: Global initiative for chronic Obstructive Lung Disease stage I-IV COPD patients electronically transmitted respiratory symptom diaries to research staff daily between December 2006 and April 2009. Respiratory symptom worsening prompted contact by a study nurse and patient assessment to determine if a cold was present or an exacerbation underway. A composite daily symptom score was derived for each subject from diarized symptom data. The exacerbation/cold/virus relation was examined using a Poisson regression model, the relation of colds to respiratory symptom severity using generalized estimating equation models. RESULTS: Daily diary transmission compliance of >97% enabled detection of all possible exacerbations. Among 262 exacerbations meeting Anthonisen criteria, 218 (83%) had cold-like symptoms present at their inception, but respiratory viruses were detected in only 106 (40%). Within-subject exacerbation risk was 30 times (95% confidence interval [CI]: 20, 47; P<0.001) greater with colds present. Compared to cold- and virus-negative exacerbations (n=57), the mean increase in composite symptom score in those cold and virus positive (n=79) was 0.93 (95% CI: 0.61, 1.25; P<0.001), cold-positive and virus-negative exacerbations (n=100) 0.51 (95% CI: 0.21, 0.81; P<0.001), cold-negative and virus-positive exacerbations (n=26) 0.58 (95% CI: 0.23, 0.94; P<0.001). CONCLUSION: This study emphasizes the importance of colds in COPD exacerbation risk and severity, even in the absence of virus detection. COPD patients should act promptly when cold symptoms appear to facilitate early intervention for exacerbation prevention or management.

Investigation of chemosensitivity during and after an acute cold.

BACKGROUND: Viral rhinitis (the "common" cold) is a frequent worldwide disease. Olfactory dysfunction is one complication that arises during infection, which in most cases heals up spontaneously upon recovery, whereas in some cases it may persist as a partial or total loss of olfaction. The aim of this prospective study was to investigate the change of other chemosensory systems during a cold. METHODS: Fifty-eight patients (age 18 to 69 years) with an acute cold were compared to a healthy control group (n = 59; age 19 to 63 years). All patients were examined on 2 occasions separated by approximately 4 weeks. Orthonasal, retronasal, gustatory, and trigeminal nasal function were investigated. Furthermore, ratings of real foods, in terms of intensity and pleasantness, were obtained. RESULTS: Compared to the control group, patients showed a decreased orthonasal (threshold and discrimination) and retronasal function. Furthermore, patients exhibited a decreased sensitivity to salt and a reduced ability to localize menthol, indicating a decreased taste and trigeminal function, respectively. Upon recovery from the infection, orthonasal olfactory and trigeminal sensitivity increased, whereas retronasal sensitivity showed no improvement and salt sensitivity decreased. CONCLUSION: This comprehensive study provides empirical evidence that chemosensory impairment is prevalent during a cold, and additionally shows for the first time that chemosensory features associated with food consumption persist postinfection.

Task Engagement and Attentional Resources.

OBJECTIVE: Two studies tested multivariate models of relationships between subjective task engagement and vigilance. The second study included a stress factor (cold infection). Modeling tested relationships between latent factors for task engagement and vigilance, and the role of engagement in mediating effects of cold infection. BACKGROUND: Raja Parasuraman's research on vigilance identified several key issues, including the roles of task factors, arousal processes, and individual differences, within the framework of resource theory. Task engagement is positively correlated with performance on various attentional tasks and may serve as a marker for resource availability. METHOD: In the first study, 229 participants performed simultaneous and successive vigilance tasks. In the second study, 204 participants performed a vigilance task and a variable-foreperiod simple reaction-time task on two separate days. On the second day, 96 participants performed while infected with a naturally occurring common cold. Task engagement was assessed in both studies. RESULTS: In both studies, vigilance decrement in hit rate was observed, and task performance led to loss of task engagement. Cold infection also depressed both vigilance and engagement. Fitting structural equation models indicated that simultaneous and successive tasks should be represented by separate latent factors (Study 1), and task engagement fully mediated the impact of cold infection on vigilance but not reaction time (Study 2). CONCLUSIONS: Modeling individual differences in task engagement elucidates the role of resources in vigilance and underscores the relevance of Parasuraman's vision of the field. APPLICATION: Assessment of task engagement may support diagnostic monitoring of operators performing tasks requiring vigilance.

Efficacy and safety of Lian-Ju-Gan-Mao capsules for treating the common cold with wind-heat syndrome: study protocol for a randomized controlled trial.

BACKGROUND: The common cold is a common and frequent respiratory disease mainly caused by viral infection of the upper respiratory tract. Chinese herbal medicine has been increasingly prescribed to treat the common cold; however, there is a lack of evidence to support the wide utility of this regimen. This protocol describes an ongoing phase II randomized controlled clinical trial, based on the theory of traditional Chinese medicine (TCM), with the objective of evaluating the efficacy and safety of Lian-Ju-Gan-Mao capsules (LJGMC), a Chinese patent medicine, compared with placebo in patients suffering from the common cold with wind-heat syndrome (CCWHS). METHODS/DESIGN: This is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial. A total of 240 patients will be recruited and randomly assigned to a high-dose group, medium-dose group, low-dose group, and placebo-matched group in a 1:1:1:1 ratio. The treatment course is 3 consecutive days, with a 5-day follow-up. The primary outcome is time to all symptoms' clearance. Secondary outcomes include time to the disappearance of primary symptoms and each secondary symptom, time to fever relief, time to fever clearance, and change in TCM symptom and sign scores. DISCUSSION: This trial is a well-designed study according to principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide high-quality evidence on the efficacy and safety of LJGMC in treating CCWHS and help to optimize the dose for the next phase III clinical trial. Moreover, the protocol presents a detailed and practical methodology for future clinical trials of drugs developed based on TCM. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-15006504 . Registered on 4 June 2015.

Efficacy and tolerability of a polysaccharide-resin-honey based cough syrup as compared to carbocysteine syrup for children with colds: a randomized, single-blinded, multicenter study.

BACKGROUND: Available pediatric treatments for acute cough are limited by lack of demonstrated efficacy. The objective of this trial is to compare the effects of a polysaccharide-resin-honey based cough syrup, and carbocysteine syrups on nocturnal and daytime cough associated with childhood upper respiratory tract infections (URIs). METHODS: Using a single-blind randomization design, the study recruited children from 4 general pediatric community clinics. Participants included 150 children aged 2 to 5 years with an URI, nocturnal and daytime cough and illness duration of ≤7 days. To be eligible, children had to be free of medication on the day before presentation. A survey was administered to parents on 4 consecutive days beginning from the day of presentation in clinic. Children received the study preparation on the first evening and then 3 times per day for 3 further days. Main outcome measures were cough frequency, cough severity, bothersome nature of cough, and quality of sleep for both child and parent. RESULTS: Both preparations were well tolerated and cough improved over the study period. After one night and on all survey days, there was a significantly better result for polysaccharide-resin-honey (P<0.05) for all the main outcome measures. The trend of improvement over the 4 days was steeper for polysaccharide-resin-honey (P<0.05) with regards to all cough parameters. CONCLUSIONS: Both polysaccharide-resin-honey and carbocysteine cough syrups were well tolerated in children over 2 years of age. The polysaccharide-resin-honey syrup was associated with a more rapid and greater improvement in all clinical cough symptoms measured, beginning from the first night of therapy. Both nocturnal and daytime cough improved, as did sleep quality for both children and parents.

Viral entry pathways: the example of common cold viruses.

For infection, viruses deliver their genomes into the host cell. These nucleic acids are usually tightly packed within the viral capsid, which, in turn, is often further enveloped within a lipid membrane. Both protect them against the hostile environment. Proteins and/or lipids on the viral particle promote attachment to the cell surface and internalization. They are likewise often involved in release of the genome inside the cell for its use as a blueprint for production of new viruses. In the following, I shall cursorily discuss the early more general steps of viral infection that include receptor recognition, uptake into the cell, and uncoating of the viral genome. The later sections will concentrate on human rhinoviruses, the main cause of the common cold, with respect to the above processes. Much of what is known on the underlying mechanisms has been worked out by Renate Fuchs at the Medical University of Vienna.

Basal salivary cortisol secretion and susceptibility to upper respiratory infection.

The immunosuppressive effects of glucocorticoids (GCs) are well-established. However, whether the net effect of GC-elicited alterations in immune function is sufficient to influence a clinically relevant outcome in healthy adults has yet to be shown. The aim of the present study was to investigate whether inter-individual differences in basal salivary cortisol production are associated with increased risk and severity of infection and subsequent illness following experimental exposure to a virus that causes the common cold. The present analyses combine archival data from three viral-challenge studies. Participants were 608 healthy adults, aged 18 to 55 years (49.2% female; 65.8% white), who each completed a three-day saliva collection protocol; was subsequently exposed to a virus that causes the common cold; and monitored for 5 days for objective signs of infection (presence of challenge virus in nasal secretions) and clinical illness (mucus weight, mucociliary clearance time). Basal cortisol production (operationalized as the calculated area-under-the-curve averaged across the 3 days) showed a graded association with infection risk, with those producing higher levels of cortisol being at greater risk. Cortisol also showed a continuous association with duration of viral shedding, an indicator of viral replication and continuing infection, such that higher cortisol concentrations predicted more days of shedding. Cortisol was not, however, related to severity of objective illness. These findings are the first to demonstrate in healthy adults an association between basal cortisol production and an objectively measured and clinically relevant infectious disease outcome.

Infection with Rhinovirus Facilitates Allergen Penetration Across a Respiratory Epithelial Cell Layer.

BACKGROUND: Rhinovirus infections are a major risk factor for asthma exacerbations. We sought to investigate in an in vitro system whether infection with human rhinovirus reduces the integrity and barrier function of a respiratory epithelial cell layer and thus may influence allergen penetration. METHODS: We cultured the human bronchial epithelial cell line 16HBE14o- in a transwell culture system as a surrogate of respiratory epithelium. The cell monolayer was infected with human rhinovirus 14 at 2 different doses. The extent and effects of transepithelial allergen penetration were assessed using transepithelial resistance measurements and a panel of (125)I-labeled purified recombinant respiratory allergens (rBet v 1, rBet v 2, and rPhl p 5). RESULTS: Infection of respiratory cell monolayers with human rhinovirus decreased transepithelial resistance and induced a pronounced increase in allergen penetration. CONCLUSIONS: Our results indicate that infection with rhinovirus damages the respiratory epithelial barrier and allows allergens to penetrate more efficiently into the subepithelial tissues where they may cause increased allergic inflammation.

Efficacy and safety of Gantong Granules in the treatment of common cold with wind-heat syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Although the common cold is generally mild and self-limiting, it is a leading cause of consultations with doctors and missed days from school and work. In light of its favorable effects of relieving symptoms and minimal side-effects, Traditional Chinese Medicine (TCM) has been widely used to treat the common cold. However, there is a lack of robust evidence to support the clinical utility of such a treatment. This study is designed to evaluate the efficacy and safety of Gantong Granules compared with placebo in patients with the common cold with wind-heat syndrome (CCWHS). METHODS/DESIGN: This is a multicenter, phase IIb, double-blind, placebo-controlled and randomized clinical trial. A total of 240 patients will be recruited, from 5 centers across China and randomly assigned to the high-dose group, medium-dose group, low-dose group or placebo control group in a 1:1:1:1 ratio. All subjects will receive the treatment for 3 to 5 days, followed by a 7-day follow-up period. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary symptoms and each symptom, time to fever relief and time to fever clearance, change in TCM symptom score, and change in Symptom and Sign Score. DISCUSSION: This trial will provide high-quality evidence on the efficacy and safety of Gantong Granules in treating CCWHS, and help to optimize the dose selection for a phase III clinical trial. TRIAL REGISTRATION: The registration number is ChiCTR-TRC-14004255 , which was assigned by the Chinese Clinical Trial Registry on 12 February 2014.

Clinical outcomes following percutaneous coronary intervention before and after introduction of drug-eluting stent.

Drug-eluting stents (DES) have demonstrated safety and efficacy in clinical outcomes, especially reduced rate of revascularization. However, it remains unknown whether clinical outcomes related to mortality improved after the introduction of DES. We sought to examine clinical outcomes including all-cause mortality, cardiovascular and non-cardiovascular death in pre-DES and DES eras. This was a single-center retrospective study including patients who underwent percutaneous coronary intervention (PCI) from August 1997 and June 2011. Study population was divided into two groups according to the time period of PCI (August 1997 to July 2004; pre-DES era, August 2004 to June 2011; DES era). The primary endpoint was all-cause mortality and secondary endpoints were cardiovascular and non-cardiovascular mortality. These endpoints were evaluated 3 years after PCI. A total of consecutive 3361 patients from our PCI cohort were analyzed. Patients in DES era were more likely to have traditional risk factors and angiographic disadvantages. The incidence of the primary endpoint was comparable between the two groups (p = 0.053). Cardiovascular and non-cardiovascular mortality were also similar between the groups (p = 0.1 and p = 0.2, respectively). Importantly, non-cardiovascular mortality accounted for over 60% of all-cause mortality in both eras. DES era was not associated with 3-year all-cause mortality, whereas DES use was associated with a reduction in 3-year cardiovascular mortality (HR 0.16, 95% CI 0.010-0.9, p = 0.035). All-cause mortality, cardiovascular and non-cardiovascular mortality at three years were comparable between pre-DES and DES era, despite the higher risk profiles of patients in DES era.