Patient presentation and physician management of upper respiratory tract infections: A retrospective review of over 5 million primary clinic consultations in Hong Kong

Background: Upper respiratory tract infection (URTI) has a significant healthcare burden worldwide. Considerable resources are consumed through health care consultations and prescribed treatment, despite evidence for little or no effect on recovery. Patterns of consultations and care including use of symptomatic medications and antibiotics for upper respiratory tract infections are poorly described. Methods. We performed a retrospective review of computerized clinical data on patients presenting to all public primary care clinics in Hong Kong with symptoms of respiratory tract infections. International Classification of Primary care (ICPC)codes used to identify patients included otitis media (H71), streptococcal pharyngitis (R72), acute URTI (R74), acute sinusitis (R75), acute tonsillitis (R76), acute laryngitis (R77), and influenza (R80). Sociodemographic variables such as gender, age, chronic illness status, attendance date, type and duration of drug prescribed were also collected. Results: Of the 5,529,755 primary care consultations for respiratory symptoms from 2005 to 2010, 98% resulted in a prescription. Prescription patterns of symptomatic medication were largely similar across the 5 years. In 2010 the mean number of drugs prescribed per consultation was 3.2, of which the commonly prescribed medication were sedating antihistamines (79.9%), analgesia (58.9%), throat lozenges (40.4%) and expectorant cough syrup (33.8%). During the study period, there was an overall decline in antibiotic prescription (8.1% to 5.1%). However, in consultations where the given diagnosis was otitis media (H71), streptococcal pharyngitis (R72), acute sinusitis (R75) or acute laryngitis (R76), over 90% resulted in antibiotic prescription. Conclusion: There was a decline in overall antibiotic prescription over the study period. However, the use of antibiotics was high in some conditions e.g. otitis media and acute laryngitis a. Multiple symptomatic medications were given for upper respiratory tract infections. Further research is needed to develop clinical and patients directed interventions to reduce the number of prescriptions of symptomatic medications and antibiotics that could reduce costs for health care services and iatrogenic risk to patients. © 2014 Kung et al.; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Prevalence of complications among Chinese diabetic patients in urban primary care clinics: A cross-sectional study

Background: A territory-wide diabetes management program (Risk Assessment Management Program - RAMP) was recently established, providing comprehensive management for all diabetics, helping to delineate current level of control and complications prevalence among primary care diabetic patients in Hong Kong. Method. This cross-sectional study captured anonymous clinical data from RAMP patients. Data obtained include sociodemographic details, type of diabetes, illness duration, family history, drug usage, coexisting illnesses, diabetic complications and other clinical parameters. Results: Data from 15,856 type 2 diabetic patients were analyzed. 57.1% were above 60 years old, with mean disease duration of 7.3 years. Hypertension was the commonest coexisting chronic illness (57.6%). 30.2% and 61.8% have their systolic and diastolic pressure controlled to below 130 mmHg and 80 mmHg respectively. Over half (51.5%) had an HbA1c level of less than 7.0%. 88.4% did not achieve target lipid level. 15% were on diet control alone. Only 22.2% were on statins. In patients with microalbuminuria and macroalbuminuria, 40.7% and 54.5% were on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) respectively. 12.9%, 38.8% and 2.4% had diabetic retinopathy, nephropathy and neuropathy respectively. Overall, 37.9%, 7.3% and 0.4% had single, two and three concurrent microvascular complications respectively. Conclusion: The level of diabetic control is comparable with other developed countries. We demonstrated a high prevalence of microvascular complications among Chinese primary care patients despite achieving adequate HbA1c levels, highlighting the importance of managing all aspects of diabetes including weight, lipid and blood pressure. Efforts to improve holistic management must be tailored according to the needs of our population, with the challenges that the majority have low educational background and in the older age group. © 2014 Kung et al.; licensee BioMed Central Ltd.link_to_subscribed_fulltex

In vitro selection of small RNA-cleaving deoxyribozymes that cleave pyrimidine–pyrimidine junctions

Herein, we sought new or improved endoribonucleases based on catalytic DNA molecules known as deoxyribozymes. The current repertoire of RNA-cleaving deoxyribozymes can cleave nearly all of the 16 possible dinucleotide junctions with rates of at least 0.1/min, with the exception of pyrimidine–pyrimidine (pyr–pyr) junctions, which are cleaved 1–3 orders of magnitude slower. We conducted four separate in vitro selection experiments to target each pyr–pyr dinucleotide combination (i.e. CC, UC, CT and UT) within a chimeric RNA/DNA substrate. We used a library of DNA molecules containing only 20 random-sequence nucleotides, so that all possible sequence permutations could be sampled in each experiment. From a total of 245 clones, we identified 22 different sequence families, of which 21 represented novel deoxyribozyme motifs. The fastest deoxyribozymes exhibited kobs values (single-turnover, intermolecular format) of 0.12/min, 0.04/min, 0.13/min and 0.15/min against CC, UC, CT and UT junctions, respectively. These values represent a 6- to 8-fold improvement for CC and UC junctions, and a 1000- to 1600-fold improvement for CT and UT junctions, compared to the best rates reported previously under identical reaction conditions. The same deoxyribozymes exhibited ∼1000-fold lower activity against all RNA substrates, but could potentially be improved through further in vitro evolution and engineering

Adults with autism overestimate the volatility of the sensory environment.

Insistence on sameness and intolerance of change are among the diagnostic criteria for autism spectrum disorder (ASD), but little research has addressed how people with ASD represent and respond to environmental change. Here, behavioral and pupillometric measurements indicated that adults with ASD are less surprised than neurotypical adults when their expectations are violated, and decreased surprise is predictive of greater symptom severity. A hierarchical Bayesian model of learning suggested that in ASD, a tendency to overlearn about volatility in the face of environmental change drives a corresponding reduction in learning about probabilistically aberrant events, thus putatively rendering these events less surprising. Participant-specific modeled estimates of surprise about environmental conditions were linked to pupil size in the ASD group, thus suggesting heightened noradrenergic responsivity in line with compromised neural gain. This study offers insights into the behavioral, algorithmic and physiological mechanisms underlying responses to environmental volatility in ASD

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Quantum Monte Carlo simulations of solids

Published versio

Conditionally Replicating Adenovirus Expressing TIMP2 Increases Survival in a Mouse Model of Disseminated Ovarian Cancer

Ovarian cancer remains difficult to treat mainly due to presentation of the disease at an advanced stage. Conditionally-replicating adenoviruses (CRAds) are promising anti-cancer agents that selectively kill the tumor cells. The present study evaluated the efficacy of a novel CRAd (Ad5/3-CXCR4-TIMP2) containing the CXCR4 promoter for selective viral replication in cancer cells together with TIMP2 as a therapeutic transgene, targeting the matrix metalloproteases (MMPs) in a murine orthotopic model of disseminated ovarian cancer. An orthotopic model of ovarian cancer was established in athymic nude mice by intraperitonal injection of the human ovarian cancer cell line, SKOV3-Luc, expressing luciferase. Upon confirmation of peritoneal dissemination of the cells by non-invasive imaging, mice were randomly divided into four treatment groups: PBS, Ad-ΔE1-TIMP2, Ad5/3-CXCR4, and Ad5/3-CXCR4-TIMP2. All mice were imaged weekly to monitor tumor growth and were sacrificed upon reaching any of the predefined endpoints, including high tumor burden and significant weight loss along with clinical evidence of pain and distress. Survival analysis was performed using the Log-rank test. The median survival for the PBS cohort was 33 days; for Ad-ΔE1-TIMP2, 39 days; for Ad5/3-CXCR4, 52.5 days; and for Ad5/3-CXCR4-TIMP2, 63 days. The TIMP2-armed CRAd delayed tumor growth and significantly increased survival when compared to the unarmed CRAd. This therapeutic effect was confirmed to be mediated through inhibition of MMP9. Results of the in vivo study support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of human patients with advanced ovarian cancer

Genomewide Expression Analysis in Zebrafish mind bomb Alleles with Pancreas Defects of Different Severity Identifies Putative Notch Responsive Genes

10.1371/journal.pone.0001479PLoS ONE3

Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from the Oncoarray Project of The International Lung Cancer Consortium

Obesity and cigarette smoking are correlated through complex relationships. Common genetic causes may contribute to these correlations. In this study, we selected 241 loci potentially associated with body mass index (BMI) based on the Genetic Investigation of ANthropometric Traits (GIANT) consortium data and calculated a BMI genetic risk score (BMI-GRS) for 17,037 individuals of European descent from the Oncoarray Project of the International Lung Cancer Consortium (ILCCO). Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016 and 0.010 before and after adjustment for BMI, respectively). The BMI-GRS was also positively correlated with pack-years of smoking (p<0.001) in smokers. Based on causal network inference analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking status and BMI/pack-years, respectively. Among them, three and four SNPs associated with smoking status and pack-years (p<0.05), respectively, were followed up in the ever-smoking data of the Tobacco, Alcohol and Genetics (TAG) consortium. Among these seven candidate SNPs, one SNP (rs11030104, BDNF) achieved statistical significance after Bonferroni correction for multiple testing, and three suggestive SNPs (rs13021737, TMEM18; rs11583200, ELAVL4; and rs6990042, SGCZ) achieved a nominal statistical significance. Our results suggest that there is a common genetic component between BMI and smoking, and pleiotropy analysis can be useful to identify novel genetic loci of complex phenotypes